From a900fa2b82b7bf70b61bedf6ffef79fd552dae70 Mon Sep 17 00:00:00 2001 From: James Li Date: Sun, 21 Jul 2024 17:57:15 -0400 Subject: [PATCH] update docs --- .../api_reference/basicfeatures.html | 586 -------- .../api_reference/cleavageprofile.html | 507 ------- _documentation/api_reference/delfi.html | 523 ------- _documentation/api_reference/endmotifs.html | 753 ---------- _documentation/api_reference/fragfile.html | 698 ---------- _documentation/api_reference/genomeutils.html | 747 ---------- _documentation/api_reference/index.html | 515 ------- _documentation/api_reference/wps.html | 578 -------- _documentation/cli_reference/index.html | 1221 ----------------- _documentation/index.html | 433 ------ _documentation/user_guide/features.html | 517 ------- _documentation/user_guide/help.html | 474 ------- _documentation/user_guide/index.html | 503 ------- _documentation/user_guide/inputdata.html | 517 ------- _documentation/user_guide/installation.html | 501 ------- 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Basic Features#

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-finaletoolkit.frag.coverage(input_file: str | TabixFile | AlignmentFile | Path, interval_file: str, output_file: str, scale_factor: float = 1000000.0, intersect_policy: str = 'midpoint', quality_threshold: int = 30, workers: int = 1, verbose: bool | int = False) → Iterable[tuple[str, int, int, str, float]]#
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Return estimated fragment coverage over intervals specified in -intervals. Fragments are read from input_file which may be -a SAM, BAM, CRAM, or Frag.gz file. Uses an algorithm where the midpoints of -fragments are calculated and coverage is tabulated from the -midpoints that fall into the specified region. Not suitable for -fragments of size approaching interval size.

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  • input_file (str or pysam.AlignmentFile) – SAM, BAM, CRAM, or Frag.gz file containing paired-end fragment -reads or its path. AlignmentFile must be opened in read mode.

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  • interval_file (str) – BED4 file containing intervals over which to generate coverage -statistics.

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  • output_file (string, optional) – Path for bed file to print coverages to. If output_file = -, -results will be printed to stdout.

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  • scale_factor (int, optional) – Amount to multiply coverages by. Default is 10^6.

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  • intersect_policy (str, optional) – Specifies how to determine whether fragments are in interval. -‘midpoint’ (default) calculates the central coordinate of each fragment -and only selects the fragment if the midpoint is in the -interval. ‘any’ includes fragments with any overlap with the -interval.

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coverages – Fragment coverages over intervals.

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Return np.ndarray containing lengths of fragments in input_file -that are above the quality threshold and are proper-paired reads.

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  • input_file (str or pysam.AlignmentFile) – BAM, SAM, or CRAM file containing paired-end fragment reads or -its path. AlignmentFile must be opened in read mode.

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  • intersect_policy (str, optional) – Specifies what policy is used to include fragments in the -given interval. Default is “midpoint”. Policies include: -- midpoint: the average of end coordinates of a fragment lies -in the interval. -- any: any part of the fragment is in the interval.

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lengths – ndarray of fragment lengths from file and contig if -specified.

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-finaletoolkit.frag.frag_length_bins(input_file: str | AlignmentFile, contig: str | None = None, start: int | None = None, stop: int | None = None, bin_size: int | None = None, output_file: str | None = None, contig_by_contig: bool = False, histogram: bool = False, intersect_policy: str = 'midpoint', quality_threshold: int = 30, verbose: bool | int = False) → tuple[ndarray, ndarray]#
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Takes input_file, computes frag lengths of fragments and returns -two arrays containing bins and counts by size. Optionally prints -data to output as a tab delimited table or histogram.

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Cleavage Profile#

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-finaletoolkit.frag.cleavage_profile(input_file: str, chrom_size: int, contig: str, start: int, stop: int, left: int = 0, right: int = 0, fraction_low: int = 1, fraction_high: int = 10000000, quality_threshold: int = 30, verbose: bool | int = 0) → ndarray#
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Cleavage profile calculated over a single interval.

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  • input_file (str) – SAM, BAM, CRAM, or FRAG file with fragment information.

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  • left (int) – Amount to subtract from start coordinate. Useful if only given -coordinates of CpG.

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cleavage_proportions – Array of cleavage proportions over given interval.

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DELFI#

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-finaletoolkit.frag.delfi(input_file: str, autosomes: str, bins_file: str, reference_file: str, blacklist_file: str = None, gap_file: Union(str, GenomeGaps) = None, output_file: str = None, gc_correct: bool = True, merge_bins: bool = True, window_size: int = 5000000, subsample_coverage: float = 2, quality_threshold: int = 30, workers: int = 1, preprocessing: bool = True, verbose: int | bool = False) → pandas.DataFrame#
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A function that replicates the methodology of Christiano et al -(2019).

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  • input_file (str) – Path string pointing to a bam file containing PE -fragment reads.

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  • autosomes (str) – Path string to a .genome file containing only autosomal -chromosomes

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  • bins_file (str) – Path string to a BED file containing 100kb bins for reference -genome of choice. Cristiano et al uses

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  • reference_file (str) – Path string to .2bit file.

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  • blacklist_file (str) – Path string to BED file containing genome blacklist.

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  • gap_file (str) – Path string to a BED4+ file where each interval is a centromere -or telomere. A bed file can be used only if the fourth field -for each entry corresponding to a telomere or centromere is -labled “telomere” or “centromere, respectively.

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  • output_file (str, optional) – Path to output tsv.

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  • window_size (int) – Size of non-overlapping windows to cover genome. Default is -5 megabases.

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  • subsample_coverage (int, optional) – The depth at which to subsample the input_bam. Default is 2.

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  • workers (int, optional) – Number of worker processes to use. Default is 1.

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End-Motifs#

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Class that stores frequencies of end-motif k-mer frequencies and -contains methods to manipulate this data.

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  • kmer_frequencies (Iterable) – A Iterable of tuples, each containing a str representing a k-mer -and a float representing its frequency

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-classmethod from_file(file_path: str | Path, quality_threshold: int, sep: str = '\t', header: int = 0) → EndMotifFreqs#
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Reads kmer frequency from a two-column tab-delimited file.

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  • header (int, optional) – Number of lines to ignore at the head of the file.

    • -
-
-
Returns:
-

kmer_freqs

-
-
Return type:
-

EndMotifFreqs

-
-
-
- -
-
-motif_diversity_score() → float#
-

Calculates a motif diversity score (MDS) using normalized -Shannon entropy as described by Jiang et al (2020). This -function is generalized for any k instead of just 4-mers.

-
- -
-
-to_tsv(output_file: str | Path, sep: str = '\t')#
-

Prints k-mer frequencies to a tsv

-
- -
- -
-
-class finaletoolkit.frag.EndMotifsIntervals(intervals: Iterable[tuple[tuple, dict]], k: int, quality_threshold: int = 20)#
-

Class that stores frequencies of end-motif k-mers over -user-specified intervals and contains methods to manipulate this -data.

-
-
Parameters:
-
    -

  • intervals (Iterable) – A collection of tuples, each containing a tuple representing -a genomic interval (chrom, 0-based start, 1-based stop) and a -dict that maps kmers to frequencies in the interval.

    • -

  • k (int) – Size of k-mers

    • -

  • quality_threshold (int, optional) – Minimum mapping quality used. Default is 30.

    • -
-
-
-
-
-freq(kmer: str) → list[tuple[str, int, int, float]]#
-

Returns a list of intervals and associated frquency for given -kmer. Results are in the form (chrom, 0-based start, 1-based -stop, frequency).

-
- -
-
-classmethod from_file(file_path: str, quality_threshold: int, sep: str = ',') → EndMotifFreqs#
-

Reads kmer frequency from a tab-delimited file. Expected columns -are contig, start, stop, name, count, *kmers. Because -exporting to file includes an option to turn counts to a fraction, -this doesn’t perfectly correspond to replicating the other file.

-
-
Parameters:
-
    -

  • file_path (str) – Path string containing path to file.

    • -

  • quality_threshold (int) – MAPQ filter used. Only used for some calculations.

    • -

  • sep (str, optional) – Delimiter used in file.

    • -
-
-
Returns:
-

kmer_freqs

-
-
Return type:
-

EndMotifFreqs

-
-
-
- -
-
-mds_bed(output_file: str | Path, sep: str = '\t')#
-

Writes MDS for each interval to a bed/bedgraph file.

-
- -
-
-motif_diversity_score() → list[tuple[tuple, float]]#
-

Calculates a motif diversity score (MDS) for each interval using -normalized Shannon entropy as described by Jiang et al (2020). This -function is generalized for any k instead of just 4-mers.

-
- -
-
-to_bed(kmer: str, output_file: str | Path, calc_freq: bool = True, sep: str = '\t')#
-

Take frequency of specified kmer and writes to BED.

-
-
Parameters:
-
    -

  • output_file (str) – File to write frequencies to.

    • -

  • calc_freq (bool, optional) – Calculates frequency of motifs if true. Otherwise, writes counts -for each motif. Default is true.

    • -

  • sep (str, optional) – Separator for table. Tab-separated by default.

    • -
-
-
-
- -
-
-to_bedgraph(kmer: str, output_file: str | Path, calc_freq: bool = True, sep: str = '\t')#
-

Take frequency of specified kmer and writes to bedgraph.

-
-
Parameters:
-
    -

  • output_file (str) – File to write frequencies to.

    • -

  • calc_freq (bool, optional) – Calculates frequency of motifs if true. Otherwise, writes counts -for each motif. Default is true.

    • -

  • sep (str, optional) – Separator for table. Tab-separated by default.

    • -
-
-
-
- -
-
-to_tsv(output_file: str | Path, calc_freq: bool = True, sep: str = '\t')#
-

Writes all intervals and associated frquencies to file. Columns -are contig, start, stop, name, count, *kmers.

-
-
Parameters:
-
    -

  • output_file (str) – File to write frequencies to.

    • -

  • calc_freq (bool, optional) – Calculates frequency of motifs if true. Otherwise, writes counts -for each motif. Default is true.

    • -

  • sep (str, optional) – Separator for table. Tab-separated by default.

    • -
-
-
-
- -
- -
-
-finaletoolkit.frag.region_end_motifs(input_file: str, contig: str, start: int, stop: int, refseq_file: str | Path, k: int = 4, fraction_low: int = 10, fraction_high: int = 600, both_strands: bool = True, output_file: None | str = None, quality_threshold: int = 20, verbose: bool | int = False) → dict#
-

Function that reads fragments in the specified region from a BAM, -SAM, or tabix indexed file and returns the 5’ k-mer (default is -4-mer) end motif counts as a dictionary. This function -reproduces the methodology of Zhou et al (2023).

-
-
Parameters:
-
    -

  • input_file (str) – Path of SAM, BAM, CRAM, or Frag.gz containing pair-end reads.

    • -

  • contig (str) – Name of contig or chromosome for region.

    • -

  • start (int) – 0-based start coordinate.

    • -

  • stop (int) – 1-based end coordinate.

    • -

  • refseq_file (str or Path) – 2bit file with reference sequence input_file was aligned to.

    • -

  • k (int, optional) – Length of end motif kmer. Default is 4.

    • -

  • fraction_low (int, optional) – Minimum fragment length.

    • -

  • fraction_high (int, optional) – Maximum fragment length.

    • -

  • both_strands (bool, optional) – Choose whether to use forward 5’ ends only or use 5’ ends for -both ends of PE reads.

    • -

  • output_file (None or str, optional)

    • -

  • quality_threshold (int, optional)

    • -

  • verbose (bool or int, optional)

    • -
-
-
Returns:
-

end_motif_freq

-
-
Return type:
-

dict

-
-
-
- -
-
-finaletoolkit.frag.end_motifs(input_file: str, refseq_file: str | Path, k: int = 4, fraction_low: int = 10, fraction_high: int = 600, both_strands: bool = False, output_file: None | str = None, quality_threshold: int = 30, workers: int = 1, verbose: bool | int = False) → EndMotifFreqs#
-

Function that reads fragments from a BAM, SAM, or tabix indexed -file and returns the 5’ k-mer (default is 4-mer) end motif -frequencies as a dictionary. Optionally writes data to a tsv. This -function reproduces the methodology of Zhou et al (2023).

-
-
Parameters:
-
    -

  • input_file (str) – SAM, BAM, CRAM, or Frag.gz file with paired-end reads.

    • -

  • refseq_file (str or Path) – 2bit file with sequence of reference genome input_file is -aligned to.

    • -

  • k (int, optional) – Length of end motif kmer. Default is 4.

    • -

  • output_file (None or str, optional) – File path to write results to. Either tsv or csv.

    • -

  • quality_threshold (int, optional) – Minimum MAPQ to filter.

    • -

  • workers (int, optional) – Number of worker processes.

    • -

  • verbose (bool or int, optional)

    • -
-
-
Returns:
-

end_motif_freq

-
-
Return type:
-

EndMotifFreqs

-
-
-
- -
-
-finaletoolkit.frag.interval_end_motifs(input_file: str, refseq_file: str | Path, intervals: str | Iterable[tuple[str, int, int, str]], k: int = 4, fraction_low: int = 10, fraction_high: int = 600, both_strands: bool = True, output_file: None | str = None, quality_threshold: int = 30, workers: int = 1, verbose: bool | int = False) → EndMotifsIntervals#
-

Function that reads fragments from a BAM, SAM, or tabix indexed -file and user-specified intervals and returns the 5’ k-mer -(default is 4-mer) end motif. Optionally writes data to a tsv.

-
-
Parameters:
-
    -

  • input_file (str) – Path of SAM, BAM, CRAM, or Frag.gz containing pair-end reads.

    • -

  • refseq_file (str or Path) – Path of 2bit file for reference genome that reads are aligned to.

    • -

  • intervals (str or tuple) – Path of BED file containing intervals or list of tuples -(chrom, start, stop, name).

    • -

  • k (int, optional) – Length of end motif kmer. Default is 4.

    • -

  • output_file (None or str, optional) – File path to write results to. Either tsv or csv.

    • -

  • quality_threshold (int, optional) – Minimum MAPQ to filter.

    • -

  • workers (int, optional) – Number of worker processes.

    • -

  • verbose (bool or int, optional)

    • -
-
-
Returns:
-

end_motif_freq

-
-
Return type:
-

EndMotifIntervals

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- - - - - - - - \ No newline at end of file diff --git a/_documentation/api_reference/fragfile.html b/_documentation/api_reference/fragfile.html deleted file mode 100644 index 100c4cc..0000000 --- a/_documentation/api_reference/fragfile.html +++ /dev/null @@ -1,698 +0,0 @@ - - - - - - - - - - - Frag File Utilities — FinaleToolkit documentation - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
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Frag File Utilities#

-
-
-finaletoolkit.utils.filter_bam(input_file: str, region_file: str | None = None, output_file: str | None = None, max_length: int | None = None, min_length: int | None = None, quality_threshold: int = 30, workers: int = 1, verbose: bool = False)#
-

Accepts the path to a BAM file and creates a bam file where all -reads are read1 in a proper pair, exceed the specified quality -threshold, do not intersect a region in the given blacklist -file, and intersects with a region in the region bed.

-
-
Parameters:
-
    -

  • input_bam (str) – Path string or AlignmentFile pointing to the BAM file to be -filtered.

    • -

  • region_file (str, option)

    • -

  • output_file (str, optional)

    • -

  • min_length (int, optional)

    • -

  • max_length (int, optional)

    • -

  • quality_threshold (int, optional)

    • -

  • workers (int, optional)

    • -

  • verbose (bool, optional)

    • -
-
-
Returns:
-

output_file

-
-
Return type:
-

str

-
-
-
- -
-
-finaletoolkit.utils.agg_bw(input_file: str, interval_file: str, output_file: str, median_window_size: int = 0, mean: bool = False, strand_location: int = 5, verbose: bool = False)#
-

Takes a BigWig and an interval BED and -aggregates signal along the intervals.

-

For aggregating WPS signals, note that the median filter trims the -ends of each interval by half of the window size of the filter -while adjusting data. There are two way this can be approached in -aggregation:

-

1. supply an interval file containing smaller intervals. e.g. if -you used 5kb intervals for WPS and used a median filter window -of 1kb, supply a BED file with 4kb windows to this function.

-

2. provide the size of the median filter window in -median_window_size along with the original intervals. e.g if -5kb intervals were used for WPS and a 1kb median filter window -was used, supply the 5kb bed file and median filter window size -to this function.

-

Do not do both of these at once.

-
-
Parameters:
-
    -

  • input_file (str)

    • -

  • interval_file (str)

    • -

  • output_file (str)

    • -

  • median_window_size (int, optional) – default is 0

    • -

  • mean (bool) – use mean instead

    • -

  • strand_location (int) – which column (starting at 0) of the interval file contains the -strand. Default is 5.

    • -

  • verbose (int or bool, optional) – default is False

    • -
-
-
Returns:
-

agg_scores

-
-
Return type:
-

NDArray

-
-
-
- -
-
-finaletoolkit.utils.chrom_sizes_to_list(chrom_sizes_file: str | Path) → list[tuple[str][int]]#
-

Reads chromosome names and sizes from a CHROMSIZE file into a list.

-
-
Parameters:
-

chrom_sizes_file (str or Path) – Tab-delimited file with column for chrom names and column for -chrom sizes.

-
-
Returns:
-

chrom names and sizes.

-
-
Return type:
-

list of string, int tuples

-
-
-
- -
-
-finaletoolkit.utils.chrom_sizes_to_dict(chrom_sizes_file: str | Path) → list[tuple[str][int]]#
-

Reads chromosome names and sizes from a CHROMSIZE file into a dict.

-
-
Parameters:
-

chrom_sizes_file (str or Path) – Tab-delimited file with column for chrom names and column for -chrom sizes.

-
-
Returns:
-

Chrom names are keys and values are int chrom sizes.

-
-
Return type:
-

dict

-
-
-
- -
-
-finaletoolkit.utils.frag_generator(input_file: str | pysam.AlignmentFile | pysam.TabixFile | Path, contig: str, quality_threshold: int = 30, start: int = None, stop: int = None, fraction_low: int = 120, fraction_high: int = 180, intersect_policy: str = 'midpoint', verbose: bool = False) → Generator[tuple]#
-

Reads from BAM, SAM, or BED file and returns tuples containing -contig (chromosome), start, stop (end), mapq, and strand for each fragment. -Optionally may filter for mapq, size, and intersection with a region.

-
-
Parameters:
-
    -

  • input_file (str or AlignmentFile)

    • -

  • contig (str)

    • -

  • quality_threshold (int, optional)

    • -

  • start (int, optional)

    • -

  • stop (int, optional)

    • -

  • fraction_low (int, optional) – Specifies lowest fragment length included in array. Default is -120, equivalent to long fraction.

    • -

  • fraction_high (int, optional) – Specifies highest fragment length included in array. Default is -120, equivalent to long fraction.

    • -

  • intersect_policy (str, optional) – Specifies what policy is used to include fragments in the -given interval. Default is “midpoint”. Policies include: -- midpoint: the average of end coordinates of a fragment lies -in the interval. -- any: any part of the fragment is in the interval.

    • -

  • verbose (bool, optional)

    • -
-
-
Returns:
-

frag_ends – Generator that yields tuples containing the region covered by -each fragment in input_file.

-
-
Return type:
-

Generator

-
-
-
- -
-
-finaletoolkit.utils.frag_array(input_file: str | AlignmentFile | TabixFile | Path, contig: str, quality_threshold: int = 30, start: int | None = None, stop: int | None = None, fraction_low: int = 120, fraction_high: int = 180, intersect_policy: str = 'midpoint', verbose: bool = False) → ndarray[Any, dtype[_ScalarType_co]]#
-

Reads from BAM, SAM, or BED file and returns a three column matrix -with fragment start and stop positions and strand.

-
-
Parameters:
-
    -

  • input_file (str or AlignmentFile)

    • -

  • contig (str)

    • -

  • quality_threshold (int, optional)

    • -

  • start (int, optional)

    • -

  • stop (int, optional)

    • -

  • fraction_low (int, optional) – Specifies lowest fragment length included in array. Default is -120, equivalent to long fraction.

    • -

  • fraction_high (int, optional) – Specifies highest fragment length included in array. Default is -120, equivalent to long fraction. -intersect_policy : str, optional -Specifies what policy is used to include fragments in the -given interval. Default is “midpoint”. Policies include: -- midpoint: the average of end coordinates of a fragment lies -in the interval. -- any: any part of the fragment is in the interval.

    • -

  • verbose (bool, optional)

    • -
-
-
Returns:
-

frag_ends – ‘NDArray’ with shape (n, 3) where column 1 contains fragment -start position and column 2 contains fragment stop position, and -column3 is 1 of on the + strand and is 0 if on the - strand. -If no fragments exist in the specified minimum-maximum interval, -the returned ‘ndarray’ will have a shape of (0, 3)

-
-
Return type:
-

NDArray

-
-
-
- -
-
-finaletoolkit.utils.low_quality_read_pairs(read, min_mapq=30)#
-

Return True if the sequenced read described in read is not a -properly paired read with a Phred score exceeding min_mapq. Based -on epifluidlab/cofragr -mmary_in_intervals.py

-

Equivalent to -F 3852 -f 3

-
-
Parameters:
-
    -

  • read (pysam.AlignedSegment) – Sequenced read to check for quality, perfect pairing and if it -is mapped.

    • -

  • min_mapq (int, optional) – Minimum Phred score for map quality of read. Defaults to 30.

    • -
-
-
Returns:
-

is_low_quality – True if read is low quality, unmapped, not properly paired.

-
-
Return type:
-

bool

-
-
-
- -
-
-finaletoolkit.utils.overlaps(contigs_1: ndarray[Any, dtype[_ScalarType_co]], starts_1: ndarray[Any, dtype[_ScalarType_co]], stops_1: ndarray[Any, dtype[_ScalarType_co]], contigs_2: ndarray[Any, dtype[_ScalarType_co]], starts_2: ndarray[Any, dtype[_ScalarType_co]], stops_2: ndarray[Any, dtype[_ScalarType_co]]) → ndarray[Any, dtype[_ScalarType_co]]#
-

Function that performs vectorized computation of overlaps. Returns -an array of same shape as contig_1 that is true if the intervals -for set 1 each have any overlap with an interval in set 2.

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Genome Utilities#

-
-
-class finaletoolkit.genome.GenomeGaps(gaps_bed: Path | str | None = None)#
-

Reads telomere, centromere, and short_arm intervals from a bed file -or generates these intervals from UCSC gap and centromere tracks for -hg19 and hg38.

-
-
-classmethod b37()#
-

Creates a GenomeGaps for the Broad Institute GRCh37 reference -genome i.e b37. This reference genome is also based on GRCh37, -but differs from the UCSC hg19 reference in a few ways, -including the absence of the ‘chr’ prefix. We generate this -GenomeGap using an ad hoc method where we take the UCSC hg19 -gap track and drop ‘chr’ from the chromosome names. Because -there are other differences between hg19 and b37, this is not -a perfect solution.

-
-
Returns:
-

gaps – GenomeGaps for the b37 reference genome.

-
-
Return type:
-

GenomeGaps

-
-
-
- -
-
-get_arm(contig: str, start: int, stop: int) → str#
-

Returns the chromosome arm the interval is in. If in -the short arm of an acrocentric chromosome or intersects a -centromere, returns an empty string.

-
-
contigstr

Chromosome of interval.

-
-
startint

Start of interval.

-
-
stopint

End of interval.

-
-
-
-
Returns:
-

arm – Arm that interval is in.

-
-
Return type:
-

str

-
-
Raises:
-

ValueError – Raised for invalid coordinates

-
-
-
- -
-
-get_contig_gaps(contig: str) → ContigGaps#
-

Creates a ContigGaps for the specified chromosome

-
-
Parameters:
-

contig (str) – Chromosome to make ContigGaps for

-
-
Returns:
-

Contains centromere and telomere intervals for chromosome

-
-
Return type:
-

ContigGaps

-
-
-
- -
-
-classmethod hg38()#
-

Creates a GenomeGaps for the hg38 reference genome. This -sequences uses chromosome names that start with ‘chr’ and is -synonymous with the GRCh38 reference genome. -:returns: gaps – GenomeGaps for the hg38 reference genome. -:rtype: GenomeGaps

-
- -
-
-in_tcmere(contig: str, start: int, stop: int) → bool#
-

Checks if specified interval is in a centromere or telomere

-
-
Parameters:
-
    -

  • contig (str) – Chromosome name

    • -

  • start (int) – Start of interval

    • -

  • stop (int) – End of interval

    • -
-
-
Returns:
-

in_telomere_or_centromere – True if in a centromere or telomere

-
-
Return type:
-

bool

-
-
-
- -
-
-overlaps_gap(contig: str, start: int, stop: int) → bool#
-

Checks if specified interval overlaps a gap interval

-
-
Parameters:
-
    -

  • contig (str) – Chromosome name

    • -

  • start (int) – Start of interval

    • -

  • stop (int) – End of interval

    • -
-
-
Returns:
-

in_telomere_or_centromere – True if in a centromere or telomere

-
-
Return type:
-

bool

-
-
-
- -
-
-to_bed(output_file: str)#
-

Prints gap intervals in GenomeGaps to a BED4 file where the name -is the type of gap interval.

-
-
Parameters:
-

output_file (str) – File to write to. Optionally gzipped. If output_file == ‘-‘, -results will be writted to stdout.

-
-
-
- -
-
-classmethod ucsc_hg19()#
-

Creates a GenomeGaps for the UCSC hg19 reference genome. This -sequences uses chromosome names that start with ‘chr’ and is -based on a version of the GRCh37 reference genome.

-
-
Returns:
-

gaps – GenomeGaps for the UCSC hg19 reference genome.

-
-
Return type:
-

GenomeGaps

-
-
-
- -
- -
-
-class finaletoolkit.genome.ContigGaps(contig: str, centromere: tuple[int, int], telomeres: Iterable[tuple[int, int]], has_short_arm: bool = False)#
-
-
-get_arm(start: int, stop: int)#
-

Returns name of chromosome arm the interval is in. Returns -“NOARM” if in a centromere, telomere, or short arm of an -acrocentric chromosome.

-
-
Parameters:
-
    -

  • start (int) – Start of interval.

    • -

  • stop (int) – End of interval.

    • -
-
-
Returns:
-

Name of the chromosome arm.

-
-
Return type:
-

str

-
-
Raises:
-

ValueError – Raised if invalid coordinates are given.

-
-
-
- -
-
-in_gap(start: int, stop: int) → bool#
-

Checks if specified interval is in a gap.

-
-
Parameters:
-
    -

  • start (int) – Start of interval.

    • -

  • stop (int) – End of Interval.

    • -
-
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Returns:
-

True if there is an overlap.

-
-
Return type:
-

bool

-
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- -
-
-in_tcmere(start: int, stop: int) → bool#
-

Checks if specified interval is in a centromere or telomere.

-
-
Parameters:
-
    -

  • start (int) – Start of interval.

    • -

  • stop (int) – End of Interval.

    • -
-
-
Returns:
-

True if there is an overlap.

-
-
Return type:
-

bool

-
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- -
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-
-finaletoolkit.genome.ucsc_hg19_gap_bed(output_file: str)#
-

Creates BED4 of centromeres, telomeres, and short arms for the UCSC -hg19 reference sequence.

-
-
Parameters:
-

output_file (str) – Output path

-
-
-
- -
-
-finaletoolkit.genome.b37_gap_bed(output_file: str)#
-

Creates BED4 of centromeres, telomeres, and short arms for the Broad -Institute GRCh37 (b37) reference sequence. Also useful for -files aligned to human_g1k_v37 (1000 Genomes Project).

-
-
Parameters:
-

output_file (str) – Output path

-
-
-
- -
-
-finaletoolkit.genome.ucsc_hg38_gap_bed(output_file: str)#
-

Creates BED4 of centromeres, telomeres, and short arms for the UCSC -hg38 reference sequence.

-
-
Parameters:
-

output_file (str) – Output path

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API#

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Window Protection Score (WPS)#

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-finaletoolkit.frag.wps(input_file: str | AlignmentFile, contig: str, start: int | str, stop: int | str, output_file: str | None = None, window_size: int = 120, fraction_low: int = 120, fraction_high: int = 180, quality_threshold: int = 30, verbose: bool | int = 0) → ndarray#
-

Return (raw) Windowed Protection Scores as specified in Snyder et al -(2016) over a region [start,stop).

-
-
Parameters:
-
    -

  • input_file (str or pysam.AlignmentFile) – BAM, SAM or tabix file containing paired-end fragment reads or its -path. AlignmentFile must be opened in read mode.

    • -

  • contig (str)

    • -

  • start (int)

    • -

  • stop (int)

    • -

  • output_file (string, optional)

    • -

  • window_size (int, optional) – Size of window to calculate WPS. Default is k = 120, equivalent -to L-WPS.

    • -

  • fraction_low (int, optional) – Specifies lowest fragment length included in calculation. -Default is 120, equivalent to long fraction.

    • -

  • fraction_high (int, optional) – Specifies highest fragment length included in calculation. -Default is 180, equivalent to long fraction.

    • -

  • quality_threshold (int, optional)

    • -

  • workers (int, optional)

    • -

  • verbose (bool, optional)

    • -
-
-
Returns:
-

scores – np struct array of with columns contig, start, and wps.

-
-
Return type:
-

numpy.ndarray

-
-
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- -
-
-finaletoolkit.frag.multi_wps(input_file: AlignmentFile | str, site_bed: str, output_file: None | str = None, window_size: int = 120, interval_size: int = 5000, fraction_low: int = 120, fraction_high: int = 180, quality_threshold: int = 30, workers: int = 1, verbose: bool | int = 0) → ndarray#
-

Function that aggregates WPS over sites in BED file according to the -method described by Snyder et al (2016).

-
-
Parameters:
-
    -

  • input_file (str or pysam.AlignmentFile) – BAM, SAM, or tabix file containing paired-end fragment reads or its -path. AlignmentFile must be opened in read mode.

    • -

  • site_bed (str) – Bed file containing intervals to perform WPS on.

    • -

  • output_file (string, optional)

    • -

  • window_size (int, optional) – Size of window to calculate WPS. Default is k = 120, equivalent -to L-WPS.

    • -

  • interval_size (int, optional) – Size of each interval specified in the bed file. Should be the -same for every interbal. Default is 5000.

    • -

  • fraction_low (int, optional) – Specifies lowest fragment length included in calculation. -Default is 120, equivalent to long fraction.

    • -

  • fraction_high (int, optional) – Specifies highest fragment length included in calculation. -Default is 120, equivalent to long fraction.

    • -

  • quality_threshold (int, optional)

    • -

  • workers (int, optional)

    • -

  • verbose (bool, optional)

    • -
-
-
Returns:
-

scores – np array of shape (n, 2) where column 1 is the coordinate and -column 2 is the score and n is the number of coordinates in -region [start,stop)

-
-
Return type:
-

numpy.ndarray

-
-
-
- -
-
-finaletoolkit.frag.adjust_wps(input_file: str, interval_file: str, output_file: str, genome_file: str, median_window_size: int = 1000, savgol_window_size: int = 21, savgol_poly_deg: int = 2, mean: bool = False, subtract_edges: bool = False, edge_size: int = 500, workers: int = 1, verbose: Union(bool, int) = False)#
-

Adjusts raw WPS data in a BigWig by applying a median filter and -Savitsky-Golay filter (Savitsky and Golay, 1964).

-
-
Parameters:
-
    -

  • input_file (str) – Path string to a BigWig containing raw WPS data.

    • -

  • interval_file (str) – BED format file containing intervals over which WPS was -calculated on.

    • -

  • output_file (str) – BigWig file to write adjusted WPS to.

    • -

  • genome_file (str) – The genome file for the reference genome that WGS was aligned -to. A tab delimited file where column 1 contains the name of -chromosomes and column 2 contains chromosome length.

    • -

  • median_window_size (int, optional) – Size of median filter window. Default is 1000.

    • -

  • savgol_window_size (int, optional) – Size of Savitsky Golay filter window. Default is 21.

    • -

  • savgol_poly_deg (int, optional) – Degree polynomial for Savitsky Golay filter. Default is 2.

    • -

  • mean (bool, optional) – If true, a mean filter is used instead of median. Default is -False.

    • -

  • subtract_edges (bool, optional) – If true, take the median of the first and last 500 bases in a -window and subtract from the whole interval. Default is False.

    • -

  • workers (int, optional) – Number of processes to use. Default is 1.

    • -

  • verbose (bool or int, optional) – Default is False.

    • -
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CLI#

-

FinaleToolkit is a package and standalone program to extract fragmentation features of cell-free DNA from paired-end sequencing data.

-

-
usage: finaletoolkit [-h] [-v]
-                     {coverage,frag-length-bins,frag-length-intervals,cleavage-profile,wps,adjust-wps,delfi,delfi-gc-correct,end-motifs,interval-end-motifs,mds,interval-mds,filter-bam,agg-bw,gap-bed}
-                     ...
-
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-

Named Arguments#

-
-
-v, --version
-

show program’s version number and exit

-
-
-
-
-

Sub-commands#

-
-

coverage#

-

Calculates fragmentation coverage over intervals defined in a BED file based on alignment data from a BAM/SAM/CRAM/Fragment file.

-
finaletoolkit coverage [-h] [-o OUTPUT_FILE] [-s SCALE_FACTOR] [-q QUALITY_THRESHOLD] [-w WORKERS] [-v] input_file interval_file
-
-
-
-

Positional Arguments#

-
-
input_file
-

Path to a BAM/SAM/CRAM/Fragment file containing fragment data.

-
-
interval_file
-

Path to a BED file containing intervals to calculate coverage over.

-
-
-
-
-

Named Arguments#

-
-
-o, --output_file
-

A BED file containing coverage values over the intervals specified in interval file.

-

Default: “-”

-
-
-s, --scale-factor
-

Scale factor for coverage values.

-

Default: 1000000.0

-
-
-q, --quality_threshold
-

Minimum mapping quality threshold.

-

Default: 30

-
-
-w, --workers
-

Number of worker processes.

-

Default: 1

-
-
-v, --verbose
-

Enable verbose mode to display detailed processing information.

-

Default: False

-
-
-
-
-
-

frag-length-bins#

-

Retrieves fragment lengths grouped in bins given a BAM/SAM/CRAM/Fragment file.

-
finaletoolkit frag-length-bins [-h] [-c CONTIG] [-S START] [-p {midpoint,any}] [-E STOP] [--bin-size BIN_SIZE] [-o OUTPUT_FILE] [--contig-by-contig] [--histogram] [-q QUALITY_THRESHOLD] [-v]
-                               input_file
-
-
-
-

Positional Arguments#

-
-
input_file
-

Path to a BAM/SAM/CRAM/Fragment file containing fragment data.

-
-
-
-
-

Named Arguments#

-
-
-c, --contig
-

Specify the contig or chromosome to select fragments from. (Required if using –start or –stop.)

-
-
-S, --start
-

Specify the 0-based left-most coordinate of the interval to select fragments from. (Must also specify –contig.)

-
-
-p, --intersect_policy
-

Possible choices: midpoint, any

-

Specifies what policy is used to include fragments in the given interval. See User Guide for more information.

-

Default: “midpoint”

-
-
-E, --stop
-

Specify the 1-based right-most coordinate of the interval to select fragments from. (Must also specify –contig.)

-
-
--bin-size
-

Specify the size of the bins to group fragment lengths into.

-
-
-o, --output_file
-

A .TSV file containing containing fragment lengths binned according to the specified bin size.

-

Default: “-”

-
-
--contig-by-contig
-

Placeholder, not implemented.

-

Default: False

-
-
--histogram
-

Enable histogram mode to display histogram in terminal.

-

Default: False

-
-
-q, --quality_threshold
-

Minimum mapping quality threshold.

-

Default: 30

-
-
-v, --verbose
-

Enable verbose mode to display detailed processing information.

-

Default: 0

-
-
-
-
-
-

frag-length-intervals#

-

Retrieves fragment length summary statistics over intervals defined in a BED file based on alignment data from a BAM/SAM/CRAM/Fragment file.

-
finaletoolkit frag-length-intervals [-h] [-p {midpoint,any}] [-o OUTPUT_FILE] [-q QUALITY_THRESHOLD] [-w WORKERS] [-v] input_file interval_file
-
-
-
-

Positional Arguments#

-
-
input_file
-

Path to a BAM/SAM/CRAM/Fragment file containing fragment data.

-
-
interval_file
-

Path to a BED file containing intervals to retrieve fragment length summary statistics over.

-
-
-
-
-

Named Arguments#

-
-
-p, --intersect_policy
-

Possible choices: midpoint, any

-

Specifies what policy is used to include fragments in the given interval. See User Guide for more information.

-

Default: “midpoint”

-
-
-o, --output-file
-

A BED file containing fragment length summary statistics (mean, median, st. dev, min, max) over the intervals specified in the interval file.

-

Default: “-”

-
-
-q, --quality-threshold
-

Minimum mapping quality threshold.

-

Default: 30

-
-
-w, --workers
-

Number of worker processes.

-

Default: 1

-
-
-v, --verbose
-

Enable verbose mode to display detailed processing information.

-

Default: 0

-
-
-
-
-
-

cleavage-profile#

-

Calculates cleavage proportion over intervals defined in a BED file based on alignment data from a BAM/SAM/CRAM/Fragment file.

-
finaletoolkit cleavage-profile [-h] [-o OUTPUT_FILE] [-lo FRACTION_LOW] [-hi FRACTION_HIGH] [-q QUALITY_THRESHOLD] [-l LEFT] [-r RIGHT] [-w WORKERS] [-v] input_file interval_file
-
-
-
-

Positional Arguments#

-
-
input_file
-

Path to a BAM/SAM/CRAM/Fragment file containing fragment data.

-
-
interval_file
-

Path to a BED file containing intervals to calculates cleavage proportion over.

-
-
-
-
-

Named Arguments#

-
-
-o, --output_file
-

A bigWig file containing the cleavage proportion results over the intervals specified in interval file.

-

Default: “-”

-
-
-lo, --fraction_low
-

Minimum length for a fragment to be included in cleavage proportion calculation.

-

Default: 120

-
-
-hi, --fraction_high
-

Maximum length for a fragment to be included in cleavage proportion calculation.

-

Default: 180

-
-
-q, --quality-threshold
-

Minimum mapping quality threshold.

-

Default: 20

-
-
-l, --left
-

Number of base pairs to subtract from start coordinate to create interval. Useful when dealing with BED files with only CpG coordinates.

-

Default: 0

-
-
-r, --right
-

Number of base pairs to add to stop coordinate to create interval. Useful when dealing with BED files with only CpG coordinates.

-

Default: 0

-
-
-w, --workers
-

Number of worker processes.

-

Default: 1

-
-
-v, --verbose
-

Enable verbose mode to display detailed processing information.

-

Default: 0

-
-
-
-
-
-

wps#

-

Calculates Windowed Protection Score (WPS) over intervals defined in a BED file based on alignment data from a BAM/SAM/CRAM/Fragment file.

-
finaletoolkit wps [-h] [-o OUTPUT_FILE] [-i INTERVAL_SIZE] [-W WINDOW_SIZE] [-lo FRACTION_LOW] [-hi FRACTION_HIGH] [-q QUALITY_THRESHOLD] [-w WORKERS] [-v] input_file site_bed
-
-
-
-

Positional Arguments#

-
-
input_file
-

Path to a BAM/SAM/CRAM/Fragment file containing fragment data.

-
-
site_bed
-

Path to a BED file containing intervals to calculate WPS over.

-
-
-
-
-

Named Arguments#

-
-
-o, --output_file
-

A bigWig file containing the WPS results over the intervals specified in interval file.

-

Default: “-”

-
-
-i, --interval_size
-

Size in bp of each interval in the interval file.

-

Default: 5000

-
-
-W, --window_size
-

Size of the sliding window used to calculate WPS scores.

-

Default: 120

-
-
-lo, --fraction_low
-

Minimum length for a fragment to be included in WPS calculation.

-

Default: 120

-
-
-hi, --fraction_high
-

Maximum length for a fragment to be included in WPS calculation.

-

Default: 180

-
-
-q, --quality_threshold
-

Minimum mapping quality threshold.

-

Default: 30

-
-
-w, --workers
-

Number of worker processes.

-

Default: 1

-
-
-v, --verbose
-

Enable verbose mode to display detailed processing information.

-

Default: 0

-
-
-
-
-
-

adjust-wps#

-

Adjusts raw Windowed Protection Score (WPS) by applying a median filter and Savitsky-Golay filter.

-
finaletoolkit adjust-wps [-h] [-o OUTPUT_FILE] [-m MEDIAN_WINDOW_SIZE] [-s SAVGOL_WINDOW_SIZE] [-p SAVGOL_POLY_DEG] [-w WORKERS] [--mean] [--subtract-edges] [-v] input_file interval_file genome_file
-
-
-
-

Positional Arguments#

-
-
input_file
-

A bigWig file containing the WPS results over the intervals specified in interval file.

-
-
interval_file
-

Path to a BED file containing intervals to WPS was calculated over.

-
-
genome_file
-

A .chrom.sizes file containing chromosome sizes.

-
-
-
-
-

Named Arguments#

-
-
-o, --output-file
-

A bigWig file containing the adjusted WPS results over the intervals specified in interval file.

-

Default: “-”

-
-
-m, --median-window-size
-

Size of the median filter window used to adjust WPS scores.

-

Default: 1000

-
-
-s, --savgol-window-size
-

Size of the Savitsky-Golay filter window used to adjust WPS scores.

-

Default: 21

-
-
-p, --savgol-poly-deg
-

Degree polynomial for Savitsky-Golay filter.

-

Default: 2

-
-
-w, --workers
-

Number of worker processes.

-

Default: 1

-
-
--mean
-

A mean filter is used instead of median.

-

Default: False

-
-
--subtract-edges
-

Take the median of the first and last 500 bases in a window and subtract from the whole interval.

-

Default: False

-
-
-v, --verbose
-

Enable verbose mode to display detailed processing information.

-
-
-
-
-
-

delfi#

-

Calculates DELFI featrues over genome, returning information about (GC-corrected) short fragments, long fragments, DELFI ratio, and total fragments. NOTE: Due to some ad hoc implementation details, currently the only accepted reference genome is hg19.

-
finaletoolkit delfi [-h] [-b BLACKLIST_FILE] [-g GAP_FILE] [-o OUTPUT_FILE] [-W WINDOW_SIZE] [-gc] [-m] [-q QUALITY_THRESHOLD] [-w WORKERS] [-v] input_file autosomes reference_file bins_file
-
-
-
-

Positional Arguments#

-
-
input_file
-

Path to a BAM/SAM/CRAM/Fragment file containing fragment data.

-
-
autosomes
-

Tab-delimited file containing (1) autosome name and (2) integer length of chromosome in base pairs.

-
-
reference_file
-

The .2bit file for the associate reference genome sequence used during alignment.

-
-
bins_file
-

A BED file containing bins over which to calculate DELFI. To replicate Cristiano et al.’s methodology, use 100kb bins over human autosomes.

-
-
-
-
-

Named Arguments#

-
-
-b, --blacklist_file
-

BED file containing regions to ignore when calculating DELFI.

-
-
-g, --gap_file
-

BED4 format file containing columns for “chrom”, “start”, “stop”, and “type”. The “type” column should denote whether the entry corresponds to a “centromere”, “telomere”, or “short arm”, and entries not falling into these categories are ignored. This information corresponds to the “gap” track for hg19 in the UCSC Genome Browser.

-
-
-o, --output_file
-

BED, bed.gz, TSV, or CSV file to write DELFI data to. If “-”, writes to stdout.

-

Default: “-”

-
-
-W, --window_size
-

Currently unused.

-

Default: 5000000

-
-
-gc, --gc_correct
-

Indicates whether to apply GC correction.

-

Default: False

-
-
-m, --merge_bins
-

Indicates whether to merge bins to 5Mb size.

-

Default: False

-
-
-q, --quality_threshold
-

Minimum mapping quality threshold.

-

Default: 30

-
-
-w, --workers
-

Number of worker processes.

-

Default: 1

-
-
-v, --verbose
-

Enable verbose mode to display detailed processing information.

-

Default: 0

-
-
-
-
-
-

delfi-gc-correct#

-

Performs gc-correction on raw delfi data.

-
finaletoolkit delfi-gc-correct [-h] [-o OUTPUT_FILE] [--header-lines HEADER_LINES] [-v] input_file
-
-
-
-

Positional Arguments#

-
-
input_file
-

BED file containing raw DELFI data. Raw DELFI data should only have columns for “contig”, “start”, “stop”, “arm”, “short”, “long”, “gc”, “num_frags”, “ratio”.

-
-
-
-
-

Named Arguments#

-
-
-o, --output-file
-

BED to print GC-corrected DELFI fractions. If “-”, will write to stdout.

-

Default: “-”

-
-
--header-lines
-

Number of header lines in BED.

-

Default: 1

-
-
-v, --verbose
-

Enable verbose mode to display detailed processing information.

-
-
-
-
-
-

end-motifs#

-

Measures frequency of k-mer 5’ end motifs.

-
finaletoolkit end-motifs [-h] [-k K] [-o OUTPUT_FILE] [-q QUALITY_THRESHOLD] [-w WORKERS] [-v] input_file refseq_file
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input_file
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Path to a BAM/SAM/CRAM/Fragment file containing fragment data.

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refseq_file
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The .2bit file for the associate reference genome sequence used during alignment.

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Length of k-mer.

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Default: 4

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TSV to print k-mer frequencies. If “-”, will write to stdout.

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Default: “-”

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Minimum mapping quality threshold.

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Default: 20

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Number of worker processes.

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Enable verbose mode to display detailed processing information.

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interval-end-motifs#

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Measures frequency of k-mer 5’ end motifs in each region specified in a BED file and writes data into a table.

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finaletoolkit interval-end-motifs [-h] [-k K] [-lo FRACTION_LOW] [-hi FRACTION_HIGH] [-o OUTPUT_FILE] [-q QUALITY_THRESHOLD] [-w WORKERS] [-v] input_file refseq_file intervals
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input_file
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Path to a BAM/SAM/CRAM/Fragment file containing fragment data.

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refseq_file
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The .2bit file for the associate reference genome sequence used during alignment.

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intervals
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Path to a BED file containing intervals to retrieve end motif frequencies over.

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Named Arguments#

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Length of k-mer.

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Minimum length for a fragment to be included in end motif frequency.

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Default: 10

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-hi, --fraction-high
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Maximum length for a fragment to be included in end motif frequency.

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Default: 600

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Path to TSV or CSV file to write end motif frequencies to.

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Default: “-”

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Minimum mapping quality threshold.

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Default: 20

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Number of worker processes.

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Enable verbose mode to display detailed processing information.

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Default: 0

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mds#

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Reads k-mer frequencies from a file and calculates a motif diversity score (MDS) using normalized Shannon entropy as described by Jiang et al (2020).

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finaletoolkit mds [-h] [-s SEP] [--header HEADER] [file_path]
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file_path
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Tab-delimited or similar file containing one column for all k-mers a one column for frequency. Reads from stdin by default.

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Default: “-”

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Separator used in tabular file.

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Default: “ “

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--header
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Number of header rows to ignore. Default is 0

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Default: 0

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interval-mds#

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Reads k-mer frequencies from a file and calculates a motif diversity score (MDS) for each interval using normalized Shannon entropy as described by Jiang et al (2020).

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finaletoolkit interval-mds [-h] [-s SEP] [file_path] file_out
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file_path
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Tab-delimited or similar file containing one column for all k-mers a one column for frequency. Reads from stdin by default.

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Default: “-”

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file_out
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Path to the output BED/BEDGraph file containing MDS for each interval.

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Default: “-”

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Separator used in tabular file.

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filter-bam#

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Filters a BAM file so that all reads are in mapped pairs, exceed a certain MAPQ, are not flagged for quality, are read1, are not secondary or supplementary alignments, and are on the same reference sequence as the mate.

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finaletoolkit filter-bam [-h] [-r REGION_FILE] [-o OUTPUT_FILE] [-q QUALITY_THRESHOLD] [-hi FRACTION_HIGH] [-lo FRACTION_LOW] [-w WORKERS] [-v] input_file
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input_file
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Path to BAM file.

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-r, --region-file
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Only output alignments overlapping the intervals in this BED file will be included.

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Output BAM file path.

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Default: “-”

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Minimum mapping quality threshold.

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Default: 30

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-hi, --fraction-high
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Maximum length for a fragment to be included in output BAM.

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-lo, --fraction-low
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Minimum length for a fragment to be included in output BAM.

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Number of worker processes.

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Default: 1

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Enable verbose mode to display detailed processing information.

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agg-bw#

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Aggregates a bigWig signal over constant-length intervals defined in a BED file.

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finaletoolkit agg-bw [-h] [-o OUTPUT_FILE] [-m MEDIAN_WINDOW_SIZE] [-v] input_file interval_file
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input_file
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A bigWig file containing signals over the intervals specified in interval file.

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interval_file
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Path to a BED file containing intervals over which signals were calculated over.

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A wiggle file containing the aggregate signal over the intervals specified in interval file.

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Default: “-”

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Size of the median filter window used to adjust WPS scores. Only modify if aggregating WPS signals.

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Default: 0

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Enable verbose mode to display detailed processing information.

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gap-bed#

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Creates a BED4 file containing centromeres, telomeres, and short-arm intervals, similar to the gaps annotation track for hg19 found on the UCSC Genome Browser (Kent et al 2002). Currently only supports hg19, b37, human_g1k_v37, hg38, and GRCh38

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finaletoolkit gap-bed [-h] {hg19,b37,human_g1k_v37,hg38,GRCh38} output_file
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reference_genome
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Possible choices: hg19, b37, human_g1k_v37, hg38, GRCh38

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Reference genome to provide gaps for.

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output_file
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Path to write BED file to. If “-” used, writes to stdout.

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Gap is used liberally in this command, and in the case hg38/GRCh38, may refer to regions where there no longer are gaps in the reference sequence.

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Features#

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FinaleToolkit has support for the following cell-free DNA features:

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Fragment Length#

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FinaleToolkit can calculate the fragment length distribution and summary statistics of cell-free DNA fragments.

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Fragment Coverage#

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FinaleToolkit can calculate fragment coverage (the number of reads mapped to a specific region of the genome). This coverage can be normalized by the total number of reads in the sample, or simply the raw value.

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Windowed Protection Score (WPS)#

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FinaleToolkit can calculate the Windowed Protection Score (WPS), which is a metric designed by Snyder et al. 2016.

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It is used to quantify the level of protection or coverage of DNA fragments across a specific genomic region. It’s calculated by assessing the number of DNA fragments that fully span a defined window (typically 120 base pairs) centered around a particular genomic coordinate, and then subtracting the number of fragments with an endpoint falling within the same window. This score is correlated with the location of nucleosomes and other genomic features, including transcriptional start sites (TSS) and DNase I hypersensitive sites (DHSs).

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DELFI#

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FinaleToolkit can calculate DELFI, which is a metric designed by Cristiano et al. 2019.

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DELFI is a metric that was introduced to identify abnormalities in cfDNA from their fragmentation patterns. In the original paper, DELFI was used to categorize patients with cancer and the associated tumor tissues of origin. The associated DELFI score is the ratio between the GC%-corrected short fragment count and the GC%-corrected long fragment count.

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End Motifs#

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FinaleToolkit can calculate the frequency of end-motif k-mers of cell-free DNA fragments. Since end motifs are specific sequences found at the ends of cfDNA fragments resulting from cleavage, they can be used to potentially detect patterns associated with certain conditions or diseases.

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Motif Diversity Score (MDS)#

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FinaleToolkit can calculate the Motif Diversity Score (MDS), which is a metric designed by Jiang et al. 2020.

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The MDS is a metric that quantifies the diversity of cfDNA end motifs. It is the normalized Shannon entropy of the categorical distribution of all possible end-motif k-mers.

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Cleavage Profile#

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FinaleToolkit can calculate the Cleavage Proportion, which is a metric designed by Zhou et al. 2022.

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The cleavage proportion is, by definition, the number of fragment ends that fall within a nucleotide location over the total number of fragment ends that overlap that nucleotide location. According to the authors, this metric shows a relationship to DNA methylation, specifically methylation at CpG sites.

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Help#

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If you think you’ve encountered a bug in FinaleToolkit, please report it on the Github issue tracker . To be useful, bug reports must include the following information:

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  • A reproducible code example that demonstrates the problem

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  • A clear explanation of why you think something is wrong

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  • The specific version of FinaleToolkit that you are working with.

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If you’ve encountered an error, searching the specific text of the message before opening a new issue can often help you solve the problem quickly and avoid making a duplicate report.

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Input Data#

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FinaleToolkit is compatible with almost any paired-end sequence data.

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SAM#

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A sequence alignment map (SAM) file is a human-readable file format that stores the results of sequence alignment. It contains information about the alignment of each read to the reference genome, as well as information about the read itself.

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BAM#

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A binary alignment file (BAM) provides the same information as a SAM file, but in a binary format. This can be useful for saving space on disk, but is not human-readable.

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FinaleToolkit requires that BAM files be BAI indexed. Therefore, you should have an associated .bam.bai file in the same directory of your input data.

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CRAM#

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A compressed read alignment map file is a compressed version of a SAM file. It is a binary file that is smaller than a BAM file, but still contains all of the same information.

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FinaleToolkit requires that CRAM files be CRAI indexed. Therefore, you should have an associated .cram.crai file in the same directory of your input data.

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Fragment File#

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A fragment file (.frag.gz) file that is derived from information in a BAM file. A fragment file is a block-gzipped BED3+2 file (similar to a tab-separated value file) that contains the following columns (with one row entry for each fragment): chrom, start, stop, mapq, and strand.

-

Here, mapq is the mapping quality of the fragment, and strand is the strand of the fragment. The strand column can be either + or -.

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FinaleToolkit requires that fragment files be Tabix indexed. Therefore, you should have an associated .frag.gz.tbi file in the same directory of your input data.

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For your reference, here is an example fragment file:

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#chrom    start    stop    mapq    strand
-chr1    10000    10050    60    +
-chr1    10050    10100    60    -
-chr1    10100    10150    60    +
-chr1    10150    10200    60    -
-chr1    10200    10250    60    +
-chr1    10250    10300    60    -
-chr1    10300    10350    60    +
-chr1    10350    10400    60    -
-chr1    10400    10450    60    +
-chr1    10450    10500    60    -
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We encourage you to use our comprehensive database, FinaleDB, to access relevant fragment files. Learn more about FinaleDB here .

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Installation#

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Prerequisites#

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The only prerequisite for installing FinaleToolkit is a Python version that is greater than 3.8.

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Installation#

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FinaleToolkit can be installed with with pip.

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Using pip:

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pip install finaletoolkit
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Also when using pip, it’s good practice to use a virtual environment, like a conda environment.

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Errors#

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If any errors arise during the installation, please fill out a detailed issue in the GitHub repository.

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If you are getting an ImportError on Mac when running FinaleToolkit, please run the following command in the terminal:

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Intersect Policy#

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When you give the Fragment Generator an interval of start and end to pull fragments from, which fragments will it return?

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What if a fragment has 1bp of overlap within the just on the edge of the window? Does it also return that fragment as well?

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These questions are answered by the intersect_policy argument, which shows up in many of the CLI and API commands.

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intersect_policy can either be midpoint or any.

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Midpoint#

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midpoint: The midpoint of the fragment determines whether the fragment will be returned or not. If the midpoint falls between start and end, then it will be returned. Else, it will not.

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Any#

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any: As long as the fragment overlaps the interval between start and end in some capacity, then it will be returned. Else, it will not.

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Quickstart#

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Getting Started#

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If not to be integrated into a workflow, FinaleToolkit is intended to be run directly from a terminal interface.

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You can open the terminal and typing the following command:

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Importing Modules#

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The FinaleToolkit package itself is divided by its API functions.

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Structure#

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While not particularly pertinent to your usage, we include this page to give you a sense of what is going on under the hood of FinaleToolkit:

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At the heart of FinaleToolkit is the Fragment Generator. This generator is designed to be as flexible as possible. It takes BAM, CRAM, SAM, and Fragment Files (among other arguments) and filters out the reads that are not of interest (e.x. unmapped reads, reads with low mapping quality, etc.). The fragments that make it through this filter are then passed to the relevant function to be processed.

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A rough outline of the structure of FinaleToolkit is therefore as follows:

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Introduction#

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Circulating cell-free DNA (cfDNA) refers to highly fragmented DNA that circulate in blood plasma. In healthy conditions, cfDNA mainly originates from hematopoietic cells through apoptosis or necrosis. In pathological states, additional cfDNA is released from the genomes of otherwise inaccessible tissues (e.g., from tumors in cancer).

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CfDNA fragmentation patterns have been established as a promising non-invasive biomarker for disease detection and monitoring. It has been shown that fragmentation pattern and cfDNA tissue-of-origin changes are associated with changes in different pathological statuses.

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Computational approaches can extract fragmentation features from cfDNA whole genome sequencing (WGS) data. However, various established cfDNA fragmentation features (ex. Windowed Protection Score (WPS), Motif Diversity Score (MDS), DELFI) have source code which is often absent, poorly documented, ad hoc, and unmaintained.

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FinaleToolkit offers a solution to this. It is a fast and comprehensive toolkit that provides a user-friendly interface to extract various cfDNA fragmentation features from fragmentation data. It is designed to be easy to use, well-documented, and maintained.

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- - - - - - - - \ No newline at end of file diff --git a/_sources/_documentation/api_reference/basicfeatures.rst.txt b/_sources/_documentation/api_reference/basicfeatures.rst.txt deleted file mode 100644 index 45ecd1b..0000000 --- a/_sources/_documentation/api_reference/basicfeatures.rst.txt +++ /dev/null @@ -1,8 +0,0 @@ -Basic Features -====================================== - -.. autofunction:: finaletoolkit.frag.coverage - -.. autofunction:: finaletoolkit.frag.frag_length - -.. autofunction:: finaletoolkit.frag.frag_length_bins \ No newline at end of file diff --git a/_sources/_documentation/api_reference/cleavageprofile.rst.txt b/_sources/_documentation/api_reference/cleavageprofile.rst.txt deleted file mode 100644 index 86df947..0000000 --- a/_sources/_documentation/api_reference/cleavageprofile.rst.txt +++ /dev/null @@ -1,5 +0,0 @@ -Cleavage Profile -====================================== -.. autofunction:: finaletoolkit.frag.cleavage_profile - - diff --git a/_sources/_documentation/api_reference/delfi.rst.txt b/_sources/_documentation/api_reference/delfi.rst.txt deleted file mode 100644 index 6cb541b..0000000 --- a/_sources/_documentation/api_reference/delfi.rst.txt +++ /dev/null @@ -1,9 +0,0 @@ -DELFI -====================================== - -.. autofunction:: finaletoolkit.frag.delfi - -.. autofunction:: finaletoolkit.frag.delfi_gc_correct - -.. autofunction:: finaletoolkit.frag.delfi_merge_bins - diff --git a/_sources/_documentation/api_reference/endmotifs.rst.txt b/_sources/_documentation/api_reference/endmotifs.rst.txt deleted file mode 100644 index 2c0f662..0000000 --- a/_sources/_documentation/api_reference/endmotifs.rst.txt +++ /dev/null @@ -1,16 +0,0 @@ -End-Motifs -====================================== - -.. autoclass:: finaletoolkit.frag.EndMotifFreqs - :members: - -.. autoclass:: finaletoolkit.frag.EndMotifsIntervals - :members: - -.. autofunction:: finaletoolkit.frag.region_end_motifs - -.. autofunction:: finaletoolkit.frag.end_motifs - -.. autofunction:: finaletoolkit.frag.interval_end_motifs - - diff --git a/_sources/_documentation/api_reference/fragfile.rst.txt b/_sources/_documentation/api_reference/fragfile.rst.txt deleted file mode 100644 index a477429..0000000 --- a/_sources/_documentation/api_reference/fragfile.rst.txt +++ /dev/null @@ -1,18 +0,0 @@ -Frag File Utilities -====================================== - -.. autofunction:: finaletoolkit.utils.filter_bam - -.. autofunction:: finaletoolkit.utils.agg_bw - -.. autofunction:: finaletoolkit.utils.chrom_sizes_to_list - -.. autofunction:: finaletoolkit.utils.chrom_sizes_to_dict - -.. autofunction:: finaletoolkit.utils.frag_generator - -.. autofunction:: finaletoolkit.utils.frag_array - -.. autofunction:: finaletoolkit.utils.low_quality_read_pairs - -.. autofunction:: finaletoolkit.utils.overlaps diff --git a/_sources/_documentation/api_reference/genomeutils.rst.txt b/_sources/_documentation/api_reference/genomeutils.rst.txt deleted file mode 100644 index 1891ef1..0000000 --- a/_sources/_documentation/api_reference/genomeutils.rst.txt +++ /dev/null @@ -1,13 +0,0 @@ -Genome Utilities -====================================== -.. autoclass:: finaletoolkit.genome.GenomeGaps - :members: - -.. autoclass:: finaletoolkit.genome.ContigGaps - :members: - -.. autofunction:: finaletoolkit.genome.ucsc_hg19_gap_bed - -.. autofunction:: finaletoolkit.genome.b37_gap_bed - -.. autofunction:: finaletoolkit.genome.ucsc_hg38_gap_bed \ No newline at end of file diff --git a/_sources/_documentation/api_reference/index.rst.txt b/_sources/_documentation/api_reference/index.rst.txt deleted file mode 100644 index e0e470b..0000000 --- a/_sources/_documentation/api_reference/index.rst.txt +++ /dev/null @@ -1,15 +0,0 @@ - -API -====== - -.. toctree:: - :maxdepth: 2 - - basicfeatures - wps - delfi - endmotifs - cleavageprofile - fragfile - genomeutils - diff --git a/_sources/_documentation/api_reference/wps.rst.txt b/_sources/_documentation/api_reference/wps.rst.txt deleted file mode 100644 index e65070c..0000000 --- a/_sources/_documentation/api_reference/wps.rst.txt +++ /dev/null @@ -1,10 +0,0 @@ -Window Protection Score (WPS) -====================================== - -.. autofunction:: finaletoolkit.frag.wps - -.. autofunction:: finaletoolkit.frag.multi_wps - -.. autofunction:: finaletoolkit.frag.adjust_wps - - diff --git a/_sources/_documentation/cli_reference/index.rst.txt b/_sources/_documentation/cli_reference/index.rst.txt deleted file mode 100644 index e8ce5b0..0000000 --- a/_sources/_documentation/cli_reference/index.rst.txt +++ /dev/null @@ -1,7 +0,0 @@ - -CLI -========================================= - -.. argparse:: - :ref: finaletoolkit.cli.main_cli.main_cli_parser - :prog: finaletoolkit \ No newline at end of file diff --git a/_sources/_documentation/index.rst.txt b/_sources/_documentation/index.rst.txt deleted file mode 100644 index 4688257..0000000 --- a/_sources/_documentation/index.rst.txt +++ /dev/null @@ -1,9 +0,0 @@ -FinaleToolkit Documentation -=========================== - -.. toctree:: - :maxdepth: 1 - - user_guide/index - cli_reference/index - api_reference/index \ No newline at end of file diff --git a/_sources/_documentation/user_guide/features.rst.txt b/_sources/_documentation/user_guide/features.rst.txt deleted file mode 100644 index 895819e..0000000 --- a/_sources/_documentation/user_guide/features.rst.txt +++ /dev/null @@ -1,56 +0,0 @@ - -Features -========================================= - -**FinaleToolkit** has support for the following cell-free DNA features: - - ------------------------ -Fragment Length ------------------------ - -**FinaleToolkit** can calculate the fragment length distribution and summary statistics of cell-free DNA fragments. - ------------------------ -Fragment Coverage ------------------------ - -**FinaleToolkit** can calculate fragment coverage (the number of reads mapped to a specific region of the genome). This coverage can be normalized by the total number of reads in the sample, or simply the raw value. - ---------------------------------- -Windowed Protection Score (WPS) ---------------------------------- - -**FinaleToolkit** can calculate the Windowed Protection Score (WPS), which is a metric designed by *Snyder et al. 2016*. - -It is used to quantify the level of protection or coverage of DNA fragments across a specific genomic region. It's calculated by assessing the number of DNA fragments that fully span a defined window (typically 120 base pairs) centered around a particular genomic coordinate, and then subtracting the number of fragments with an endpoint falling within the same window. This score is correlated with the location of nucleosomes and other genomic features, including transcriptional start sites (TSS) and DNase I hypersensitive sites (DHSs). - ------------------------ -DELFI ------------------------ - -**FinaleToolkit** can calculate DELFI, which is a metric designed by *Cristiano et al. 2019*. - -DELFI is a metric that was introduced to identify abnormalities in cfDNA from their fragmentation patterns. In the original paper, DELFI was used to categorize patients with cancer and the associated tumor tissues of origin. The associated DELFI score is the ratio between the GC%-corrected short fragment count and the GC%-corrected long fragment count. - ------------------------ -End Motifs ------------------------ - -**FinaleToolkit** can calculate the frequency of end-motif k-mers of cell-free DNA fragments. Since end motifs are specific sequences found at the ends of cfDNA fragments resulting from cleavage, they can be used to potentially detect patterns associated with certain conditions or diseases. - ------------------------------ -Motif Diversity Score (MDS) ------------------------------ - -**FinaleToolkit** can calculate the Motif Diversity Score (MDS), which is a metric designed by *Jiang et al. 2020*. - -The MDS is a metric that quantifies the diversity of cfDNA end motifs. It is the normalized Shannon entropy of the categorical distribution of all possible end-motif k-mers. - ------------------------ -Cleavage Profile ------------------------ - -**FinaleToolkit** can calculate the Cleavage Proportion, which is a metric designed by *Zhou et al. 2022*. - -The cleavage proportion is, by definition, the number of fragment ends that fall within a nucleotide location over the total number of fragment ends that overlap that nucleotide location. According to the authors, this metric shows a relationship to DNA methylation, specifically methylation at CpG sites. \ No newline at end of file diff --git a/_sources/_documentation/user_guide/help.rst.txt b/_sources/_documentation/user_guide/help.rst.txt deleted file mode 100644 index 4b992ba..0000000 --- a/_sources/_documentation/user_guide/help.rst.txt +++ /dev/null @@ -1,12 +0,0 @@ - -Help -========================================= - -If you think you’ve encountered a bug in **FinaleToolkit**, please report it on the `Github issue tracker `_ . To be useful, bug reports must include the following information: - -- A reproducible code example that demonstrates the problem -- The output that you are seeing (ex. the error message) -- A clear explanation of why you think something is wrong -- The specific version of **FinaleToolkit** that you are working with. - -If you’ve encountered an error, searching the specific text of the message before opening a new issue can often help you solve the problem quickly and avoid making a duplicate report. diff --git a/_sources/_documentation/user_guide/index.rst.txt b/_sources/_documentation/user_guide/index.rst.txt deleted file mode 100644 index 23b2ed9..0000000 --- a/_sources/_documentation/user_guide/index.rst.txt +++ /dev/null @@ -1,15 +0,0 @@ - -User Guide -========================================= - -.. toctree:: - :maxdepth: 2 - - what - inputdata - features - installation - structure - intersectpolicy - quickstart - help \ No newline at end of file diff --git a/_sources/_documentation/user_guide/inputdata.rst.txt b/_sources/_documentation/user_guide/inputdata.rst.txt deleted file mode 100644 index 97e00f4..0000000 --- a/_sources/_documentation/user_guide/inputdata.rst.txt +++ /dev/null @@ -1,49 +0,0 @@ - -Input Data -========================================= - -**FinaleToolkit** is compatible with almost any paired-end sequence data. - -SAM -^^^^^^^^^^^ - -A sequence alignment map (SAM) file is a human-readable file format that stores the results of sequence alignment. It contains information about the alignment of each read to the reference genome, as well as information about the read itself. - -BAM -^^^^^^^^^^^ - -A binary alignment file (BAM) provides the same information as a SAM file, but in a binary format. This can be useful for saving space on disk, but is not human-readable. - -**FinaleToolkit** requires that BAM files be BAI indexed. Therefore, you should have an associated ``.bam.bai`` file in the same directory of your input data. - -CRAM -^^^^^^^^^^^ - -A compressed read alignment map file is a compressed version of a SAM file. It is a binary file that is smaller than a BAM file, but still contains all of the same information. - -**FinaleToolkit** requires that CRAM files be CRAI indexed. Therefore, you should have an associated ``.cram.crai`` file in the same directory of your input data. - -Fragment File -^^^^^^^^^^^^^^^^ - -A fragment file (`.frag.gz`) file that is derived from information in a BAM file. A fragment file is a block-gzipped BED3+2 file (similar to a tab-separated value file) that contains the following columns (with one row entry for each fragment): ``chrom``, ``start``, ``stop``, ``mapq``, and ``strand``. - -Here, ``mapq`` is the mapping quality of the fragment, and ``strand`` is the strand of the fragment. The ``strand`` column can be either ``+`` or ``-``. - -**FinaleToolkit** requires that fragment files be Tabix indexed. Therefore, you should have an associated ``.frag.gz.tbi`` file in the same directory of your input data. - -For your reference, here is an example fragment file:: - - #chrom start stop mapq strand - chr1 10000 10050 60 + - chr1 10050 10100 60 - - chr1 10100 10150 60 + - chr1 10150 10200 60 - - chr1 10200 10250 60 + - chr1 10250 10300 60 - - chr1 10300 10350 60 + - chr1 10350 10400 60 - - chr1 10400 10450 60 + - chr1 10450 10500 60 - - -We encourage you to use our comprehensive database, **FinaleDB**, to access relevant fragment files. Learn more about **FinaleDB** `here `_ . \ No newline at end of file diff --git a/_sources/_documentation/user_guide/installation.rst.txt b/_sources/_documentation/user_guide/installation.rst.txt deleted file mode 100644 index ab857b1..0000000 --- a/_sources/_documentation/user_guide/installation.rst.txt +++ /dev/null @@ -1,29 +0,0 @@ -========================== -Installation -========================== - ------------------------ -Prerequisites ------------------------ -The only prerequisite for installing **FinaleToolkit** is a Python version that is greater than ``3.8``. - ----------------------- -Installation ----------------------- -**FinaleToolkit** can be installed with with ``pip``. - -Using ``pip``:: - - pip install finaletoolkit - -Also when using ``pip``, it’s good practice to use a virtual environment, like a ``conda`` environment. - ------------------- -Errors ------------------- - -If any errors arise during the installation, please fill out a detailed issue in the GitHub repository. - -If you are getting an ``ImportError`` on Mac when running **FinaleToolkit**, please run the following command in the terminal:: - - $ brew install curl \ No newline at end of file diff --git a/_sources/_documentation/user_guide/intersectpolicy.rst.txt b/_sources/_documentation/user_guide/intersectpolicy.rst.txt deleted file mode 100644 index c0572cb..0000000 --- a/_sources/_documentation/user_guide/intersectpolicy.rst.txt +++ /dev/null @@ -1,21 +0,0 @@ -========================== -Intersect Policy -========================== - -When you give the ``Fragment Generator`` an interval of ``start`` and ``end`` to pull fragments from, which fragments will it return? - -What if a fragment has 1bp of overlap within the just on the edge of the window? Does it also return that fragment as well? - -These questions are answered by the ``intersect_policy`` argument, which shows up in many of the CLI and API commands. - -``intersect_policy`` can either be ``midpoint`` or ``any``. - -Midpoint ----------------- - -``midpoint``: The midpoint of the fragment determines whether the fragment will be returned or not. If the midpoint falls between ``start`` and ``end``, then it will be returned. Else, it will not. - -Any -------- - -``any``: As long as the fragment overlaps the interval between ``start`` and ``end`` in some capacity, then it will be returned. Else, it will not. \ No newline at end of file diff --git a/_sources/_documentation/user_guide/quickstart.rst.txt b/_sources/_documentation/user_guide/quickstart.rst.txt deleted file mode 100644 index 083554c..0000000 --- a/_sources/_documentation/user_guide/quickstart.rst.txt +++ /dev/null @@ -1,29 +0,0 @@ - -Quickstart -========================================= - ------------------------- -Getting Started ------------------------- - -If not to be integrated into a workflow, **FinaleToolkit** is intended to be run directly from a terminal interface. - -You can open the terminal and typing the following command:: - - $ finaletoolkit - ------------------------- -Importing Modules ------------------------- - -The **FinaleToolkit** package itself is divided by its API functions. - -You can load *all* of the functions by using the following command:: - - >>> import finaletoolkit as ft - -If you want to load a *specific* function, you can do so by using the following: - -Assuming we wanted to load the DELFI function:: - - >>> from finaletoolkit.frag import delfi diff --git a/_sources/_documentation/user_guide/structure.rst.txt b/_sources/_documentation/user_guide/structure.rst.txt deleted file mode 100644 index 615ea3d..0000000 --- a/_sources/_documentation/user_guide/structure.rst.txt +++ /dev/null @@ -1,12 +0,0 @@ - -Structure -========================================= - -While not particularly pertinent to your usage, we include this page to give you a sense of what is going on under the hood of **FinaleToolkit**: - -At the heart of **FinaleToolkit** is the ``Fragment Generator``. This generator is designed to be as flexible as possible. It takes BAM, CRAM, SAM, and Fragment Files (among other arguments) and filters out the reads that are not of interest (e.x. unmapped reads, reads with low mapping quality, etc.). The fragments that make it through this filter are then passed to the relevant function to be processed. - -A rough outline of the structure of **FinaleToolkit** is therefore as follows: - -.. figure:: finaletoolkit_structure.png - :align: center \ No newline at end of file diff --git a/_sources/_documentation/user_guide/what.rst.txt b/_sources/_documentation/user_guide/what.rst.txt deleted file mode 100644 index c233676..0000000 --- a/_sources/_documentation/user_guide/what.rst.txt +++ /dev/null @@ -1,11 +0,0 @@ - -Introduction -========================================= - -Circulating cell-free DNA (cfDNA) refers to highly fragmented DNA that circulate in blood plasma. In healthy conditions, cfDNA mainly originates from hematopoietic cells through apoptosis or necrosis. In pathological states, additional cfDNA is released from the genomes of otherwise inaccessible tissues (e.g., from tumors in cancer). - -CfDNA fragmentation patterns have been established as a promising non-invasive biomarker for disease detection and monitoring. It has been shown that fragmentation pattern and cfDNA tissue-of-origin changes are associated with changes in different pathological statuses. - -Computational approaches can extract fragmentation features from cfDNA whole genome sequencing (WGS) data. However, various established cfDNA fragmentation features (ex. Windowed Protection Score (WPS), Motif Diversity Score (MDS), DELFI) have source code which is often absent, poorly documented, ad hoc, and unmaintained. - -**FinaleToolkit** offers a solution to this. It is a fast and comprehensive toolkit that provides a user-friendly interface to extract various cfDNA fragmentation features from fragmentation data. It is designed to be easy to use, well-documented, and maintained. \ No newline at end of file diff --git a/_sources/source/api_reference/basicfeatures.rst.txt b/_sources/source/api_reference/basicfeatures.rst.txt deleted file mode 100644 index 45ecd1b..0000000 --- a/_sources/source/api_reference/basicfeatures.rst.txt +++ /dev/null @@ -1,8 +0,0 @@ -Basic Features -====================================== - -.. autofunction:: finaletoolkit.frag.coverage - -.. autofunction:: finaletoolkit.frag.frag_length - -.. autofunction:: finaletoolkit.frag.frag_length_bins \ No newline at end of file diff --git a/_sources/source/api_reference/cleavageprofile.rst.txt b/_sources/source/api_reference/cleavageprofile.rst.txt deleted file mode 100644 index 86df947..0000000 --- a/_sources/source/api_reference/cleavageprofile.rst.txt +++ /dev/null @@ -1,5 +0,0 @@ -Cleavage Profile -====================================== -.. autofunction:: finaletoolkit.frag.cleavage_profile - - diff --git a/_sources/source/api_reference/delfi.rst.txt b/_sources/source/api_reference/delfi.rst.txt deleted file mode 100644 index 6cb541b..0000000 --- a/_sources/source/api_reference/delfi.rst.txt +++ /dev/null @@ -1,9 +0,0 @@ -DELFI -====================================== - -.. autofunction:: finaletoolkit.frag.delfi - -.. autofunction:: finaletoolkit.frag.delfi_gc_correct - -.. autofunction:: finaletoolkit.frag.delfi_merge_bins - diff --git a/_sources/source/api_reference/endmotifs.rst.txt b/_sources/source/api_reference/endmotifs.rst.txt deleted file mode 100644 index 2c0f662..0000000 --- a/_sources/source/api_reference/endmotifs.rst.txt +++ /dev/null @@ -1,16 +0,0 @@ -End-Motifs -====================================== - -.. autoclass:: finaletoolkit.frag.EndMotifFreqs - :members: - -.. autoclass:: finaletoolkit.frag.EndMotifsIntervals - :members: - -.. autofunction:: finaletoolkit.frag.region_end_motifs - -.. autofunction:: finaletoolkit.frag.end_motifs - -.. autofunction:: finaletoolkit.frag.interval_end_motifs - - diff --git a/_sources/source/api_reference/fragfile.rst.txt b/_sources/source/api_reference/fragfile.rst.txt deleted file mode 100644 index a477429..0000000 --- a/_sources/source/api_reference/fragfile.rst.txt +++ /dev/null @@ -1,18 +0,0 @@ -Frag File Utilities -====================================== - -.. autofunction:: finaletoolkit.utils.filter_bam - -.. autofunction:: finaletoolkit.utils.agg_bw - -.. autofunction:: finaletoolkit.utils.chrom_sizes_to_list - -.. autofunction:: finaletoolkit.utils.chrom_sizes_to_dict - -.. autofunction:: finaletoolkit.utils.frag_generator - -.. autofunction:: finaletoolkit.utils.frag_array - -.. autofunction:: finaletoolkit.utils.low_quality_read_pairs - -.. autofunction:: finaletoolkit.utils.overlaps diff --git a/_sources/source/api_reference/genomeutils.rst.txt b/_sources/source/api_reference/genomeutils.rst.txt deleted file mode 100644 index 1891ef1..0000000 --- a/_sources/source/api_reference/genomeutils.rst.txt +++ /dev/null @@ -1,13 +0,0 @@ -Genome Utilities -====================================== -.. autoclass:: finaletoolkit.genome.GenomeGaps - :members: - -.. autoclass:: finaletoolkit.genome.ContigGaps - :members: - -.. autofunction:: finaletoolkit.genome.ucsc_hg19_gap_bed - -.. autofunction:: finaletoolkit.genome.b37_gap_bed - -.. autofunction:: finaletoolkit.genome.ucsc_hg38_gap_bed \ No newline at end of file diff --git a/_sources/source/api_reference/index.rst.txt b/_sources/source/api_reference/index.rst.txt deleted file mode 100644 index e0e470b..0000000 --- a/_sources/source/api_reference/index.rst.txt +++ /dev/null @@ -1,15 +0,0 @@ - -API -====== - -.. toctree:: - :maxdepth: 2 - - basicfeatures - wps - delfi - endmotifs - cleavageprofile - fragfile - genomeutils - diff --git a/_sources/source/api_reference/wps.rst.txt b/_sources/source/api_reference/wps.rst.txt deleted file mode 100644 index e65070c..0000000 --- a/_sources/source/api_reference/wps.rst.txt +++ /dev/null @@ -1,10 +0,0 @@ -Window Protection Score (WPS) -====================================== - -.. autofunction:: finaletoolkit.frag.wps - -.. autofunction:: finaletoolkit.frag.multi_wps - -.. autofunction:: finaletoolkit.frag.adjust_wps - - diff --git a/_sources/source/cli_reference/index.rst.txt b/_sources/source/cli_reference/index.rst.txt deleted file mode 100644 index e8ce5b0..0000000 --- a/_sources/source/cli_reference/index.rst.txt +++ /dev/null @@ -1,7 +0,0 @@ - -CLI -========================================= - -.. argparse:: - :ref: finaletoolkit.cli.main_cli.main_cli_parser - :prog: finaletoolkit \ No newline at end of file diff --git a/_sources/source/index.rst.txt b/_sources/source/index.rst.txt deleted file mode 100644 index 4688257..0000000 --- a/_sources/source/index.rst.txt +++ /dev/null @@ -1,9 +0,0 @@ -FinaleToolkit Documentation -=========================== - -.. toctree:: - :maxdepth: 1 - - user_guide/index - cli_reference/index - api_reference/index \ No newline at end of file diff --git a/_sources/source/user_guide/features.rst.txt b/_sources/source/user_guide/features.rst.txt deleted file mode 100644 index 895819e..0000000 --- a/_sources/source/user_guide/features.rst.txt +++ /dev/null @@ -1,56 +0,0 @@ - -Features -========================================= - -**FinaleToolkit** has support for the following cell-free DNA features: - - ------------------------ -Fragment Length ------------------------ - -**FinaleToolkit** can calculate the fragment length distribution and summary statistics of cell-free DNA fragments. - ------------------------ -Fragment Coverage ------------------------ - -**FinaleToolkit** can calculate fragment coverage (the number of reads mapped to a specific region of the genome). This coverage can be normalized by the total number of reads in the sample, or simply the raw value. - ---------------------------------- -Windowed Protection Score (WPS) ---------------------------------- - -**FinaleToolkit** can calculate the Windowed Protection Score (WPS), which is a metric designed by *Snyder et al. 2016*. - -It is used to quantify the level of protection or coverage of DNA fragments across a specific genomic region. It's calculated by assessing the number of DNA fragments that fully span a defined window (typically 120 base pairs) centered around a particular genomic coordinate, and then subtracting the number of fragments with an endpoint falling within the same window. This score is correlated with the location of nucleosomes and other genomic features, including transcriptional start sites (TSS) and DNase I hypersensitive sites (DHSs). - ------------------------ -DELFI ------------------------ - -**FinaleToolkit** can calculate DELFI, which is a metric designed by *Cristiano et al. 2019*. - -DELFI is a metric that was introduced to identify abnormalities in cfDNA from their fragmentation patterns. In the original paper, DELFI was used to categorize patients with cancer and the associated tumor tissues of origin. The associated DELFI score is the ratio between the GC%-corrected short fragment count and the GC%-corrected long fragment count. - ------------------------ -End Motifs ------------------------ - -**FinaleToolkit** can calculate the frequency of end-motif k-mers of cell-free DNA fragments. Since end motifs are specific sequences found at the ends of cfDNA fragments resulting from cleavage, they can be used to potentially detect patterns associated with certain conditions or diseases. - ------------------------------ -Motif Diversity Score (MDS) ------------------------------ - -**FinaleToolkit** can calculate the Motif Diversity Score (MDS), which is a metric designed by *Jiang et al. 2020*. - -The MDS is a metric that quantifies the diversity of cfDNA end motifs. It is the normalized Shannon entropy of the categorical distribution of all possible end-motif k-mers. - ------------------------ -Cleavage Profile ------------------------ - -**FinaleToolkit** can calculate the Cleavage Proportion, which is a metric designed by *Zhou et al. 2022*. - -The cleavage proportion is, by definition, the number of fragment ends that fall within a nucleotide location over the total number of fragment ends that overlap that nucleotide location. According to the authors, this metric shows a relationship to DNA methylation, specifically methylation at CpG sites. \ No newline at end of file diff --git a/_sources/source/user_guide/help.rst.txt b/_sources/source/user_guide/help.rst.txt deleted file mode 100644 index 4b992ba..0000000 --- a/_sources/source/user_guide/help.rst.txt +++ /dev/null @@ -1,12 +0,0 @@ - -Help -========================================= - -If you think you’ve encountered a bug in **FinaleToolkit**, please report it on the `Github issue tracker `_ . To be useful, bug reports must include the following information: - -- A reproducible code example that demonstrates the problem -- The output that you are seeing (ex. the error message) -- A clear explanation of why you think something is wrong -- The specific version of **FinaleToolkit** that you are working with. - -If you’ve encountered an error, searching the specific text of the message before opening a new issue can often help you solve the problem quickly and avoid making a duplicate report. diff --git a/_sources/source/user_guide/index.rst.txt b/_sources/source/user_guide/index.rst.txt deleted file mode 100644 index 23b2ed9..0000000 --- a/_sources/source/user_guide/index.rst.txt +++ /dev/null @@ -1,15 +0,0 @@ - -User Guide -========================================= - -.. toctree:: - :maxdepth: 2 - - what - inputdata - features - installation - structure - intersectpolicy - quickstart - help \ No newline at end of file diff --git a/_sources/source/user_guide/inputdata.rst.txt b/_sources/source/user_guide/inputdata.rst.txt deleted file mode 100644 index 97e00f4..0000000 --- a/_sources/source/user_guide/inputdata.rst.txt +++ /dev/null @@ -1,49 +0,0 @@ - -Input Data -========================================= - -**FinaleToolkit** is compatible with almost any paired-end sequence data. - -SAM -^^^^^^^^^^^ - -A sequence alignment map (SAM) file is a human-readable file format that stores the results of sequence alignment. It contains information about the alignment of each read to the reference genome, as well as information about the read itself. - -BAM -^^^^^^^^^^^ - -A binary alignment file (BAM) provides the same information as a SAM file, but in a binary format. This can be useful for saving space on disk, but is not human-readable. - -**FinaleToolkit** requires that BAM files be BAI indexed. Therefore, you should have an associated ``.bam.bai`` file in the same directory of your input data. - -CRAM -^^^^^^^^^^^ - -A compressed read alignment map file is a compressed version of a SAM file. It is a binary file that is smaller than a BAM file, but still contains all of the same information. - -**FinaleToolkit** requires that CRAM files be CRAI indexed. Therefore, you should have an associated ``.cram.crai`` file in the same directory of your input data. - -Fragment File -^^^^^^^^^^^^^^^^ - -A fragment file (`.frag.gz`) file that is derived from information in a BAM file. A fragment file is a block-gzipped BED3+2 file (similar to a tab-separated value file) that contains the following columns (with one row entry for each fragment): ``chrom``, ``start``, ``stop``, ``mapq``, and ``strand``. - -Here, ``mapq`` is the mapping quality of the fragment, and ``strand`` is the strand of the fragment. The ``strand`` column can be either ``+`` or ``-``. - -**FinaleToolkit** requires that fragment files be Tabix indexed. Therefore, you should have an associated ``.frag.gz.tbi`` file in the same directory of your input data. - -For your reference, here is an example fragment file:: - - #chrom start stop mapq strand - chr1 10000 10050 60 + - chr1 10050 10100 60 - - chr1 10100 10150 60 + - chr1 10150 10200 60 - - chr1 10200 10250 60 + - chr1 10250 10300 60 - - chr1 10300 10350 60 + - chr1 10350 10400 60 - - chr1 10400 10450 60 + - chr1 10450 10500 60 - - -We encourage you to use our comprehensive database, **FinaleDB**, to access relevant fragment files. Learn more about **FinaleDB** `here `_ . \ No newline at end of file diff --git a/_sources/source/user_guide/installation.rst.txt b/_sources/source/user_guide/installation.rst.txt deleted file mode 100644 index ab857b1..0000000 --- a/_sources/source/user_guide/installation.rst.txt +++ /dev/null @@ -1,29 +0,0 @@ -========================== -Installation -========================== - ------------------------ -Prerequisites ------------------------ -The only prerequisite for installing **FinaleToolkit** is a Python version that is greater than ``3.8``. - ----------------------- -Installation ----------------------- -**FinaleToolkit** can be installed with with ``pip``. - -Using ``pip``:: - - pip install finaletoolkit - -Also when using ``pip``, it’s good practice to use a virtual environment, like a ``conda`` environment. - ------------------- -Errors ------------------- - -If any errors arise during the installation, please fill out a detailed issue in the GitHub repository. - -If you are getting an ``ImportError`` on Mac when running **FinaleToolkit**, please run the following command in the terminal:: - - $ brew install curl \ No newline at end of file diff --git a/_sources/source/user_guide/intersectpolicy.rst.txt b/_sources/source/user_guide/intersectpolicy.rst.txt deleted file mode 100644 index c0572cb..0000000 --- a/_sources/source/user_guide/intersectpolicy.rst.txt +++ /dev/null @@ -1,21 +0,0 @@ -========================== -Intersect Policy -========================== - -When you give the ``Fragment Generator`` an interval of ``start`` and ``end`` to pull fragments from, which fragments will it return? - -What if a fragment has 1bp of overlap within the just on the edge of the window? Does it also return that fragment as well? - -These questions are answered by the ``intersect_policy`` argument, which shows up in many of the CLI and API commands. - -``intersect_policy`` can either be ``midpoint`` or ``any``. - -Midpoint ----------------- - -``midpoint``: The midpoint of the fragment determines whether the fragment will be returned or not. If the midpoint falls between ``start`` and ``end``, then it will be returned. Else, it will not. - -Any -------- - -``any``: As long as the fragment overlaps the interval between ``start`` and ``end`` in some capacity, then it will be returned. Else, it will not. \ No newline at end of file diff --git a/_sources/source/user_guide/quickstart.rst.txt b/_sources/source/user_guide/quickstart.rst.txt deleted file mode 100644 index 083554c..0000000 --- a/_sources/source/user_guide/quickstart.rst.txt +++ /dev/null @@ -1,29 +0,0 @@ - -Quickstart -========================================= - ------------------------- -Getting Started ------------------------- - -If not to be integrated into a workflow, **FinaleToolkit** is intended to be run directly from a terminal interface. - -You can open the terminal and typing the following command:: - - $ finaletoolkit - ------------------------- -Importing Modules ------------------------- - -The **FinaleToolkit** package itself is divided by its API functions. - -You can load *all* of the functions by using the following command:: - - >>> import finaletoolkit as ft - -If you want to load a *specific* function, you can do so by using the following: - -Assuming we wanted to load the DELFI function:: - - >>> from finaletoolkit.frag import delfi diff --git a/_sources/source/user_guide/structure.rst.txt b/_sources/source/user_guide/structure.rst.txt deleted file mode 100644 index 615ea3d..0000000 --- a/_sources/source/user_guide/structure.rst.txt +++ /dev/null @@ -1,12 +0,0 @@ - -Structure -========================================= - -While not particularly pertinent to your usage, we include this page to give you a sense of what is going on under the hood of **FinaleToolkit**: - -At the heart of **FinaleToolkit** is the ``Fragment Generator``. This generator is designed to be as flexible as possible. It takes BAM, CRAM, SAM, and Fragment Files (among other arguments) and filters out the reads that are not of interest (e.x. unmapped reads, reads with low mapping quality, etc.). The fragments that make it through this filter are then passed to the relevant function to be processed. - -A rough outline of the structure of **FinaleToolkit** is therefore as follows: - -.. figure:: finaletoolkit_structure.png - :align: center \ No newline at end of file diff --git a/_sources/source/user_guide/what.rst.txt b/_sources/source/user_guide/what.rst.txt deleted file mode 100644 index c233676..0000000 --- a/_sources/source/user_guide/what.rst.txt +++ /dev/null @@ -1,11 +0,0 @@ - -Introduction -========================================= - -Circulating cell-free DNA (cfDNA) refers to highly fragmented DNA that circulate in blood plasma. In healthy conditions, cfDNA mainly originates from hematopoietic cells through apoptosis or necrosis. In pathological states, additional cfDNA is released from the genomes of otherwise inaccessible tissues (e.g., from tumors in cancer). - -CfDNA fragmentation patterns have been established as a promising non-invasive biomarker for disease detection and monitoring. It has been shown that fragmentation pattern and cfDNA tissue-of-origin changes are associated with changes in different pathological statuses. - -Computational approaches can extract fragmentation features from cfDNA whole genome sequencing (WGS) data. However, various established cfDNA fragmentation features (ex. Windowed Protection Score (WPS), Motif Diversity Score (MDS), DELFI) have source code which is often absent, poorly documented, ad hoc, and unmaintained. - -**FinaleToolkit** offers a solution to this. It is a fast and comprehensive toolkit that provides a user-friendly interface to extract various cfDNA fragmentation features from fragmentation data. 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SW@ke+i9ap#|HA+S0001);};|V diff --git a/documentation/cli_reference/index.html b/documentation/cli_reference/index.html index 9e40f2f..a2428d2 100644 --- a/documentation/cli_reference/index.html +++ b/documentation/cli_reference/index.html @@ -389,7 +389,9 @@

    Sub-commands

    coverage#

    Calculates fragmentation coverage over intervals defined in a BED file based on alignment data from a BAM/SAM/CRAM/Fragment file.

    -
    finaletoolkit coverage [-h] [-o OUTPUT_FILE] [-s SCALE_FACTOR] [-q QUALITY_THRESHOLD] [-w WORKERS] [-v] input_file interval_file
+
    finaletoolkit coverage [-h] [-o OUTPUT_FILE] [-s SCALE_FACTOR] [-q QUALITY_THRESHOLD]
+                       [-w WORKERS] [-v]
+                       input_file interval_file
 
    
 
    
 
    
@@ -432,8 +434,9 @@ 
    Named Arguments
 
    frag-length-bins#
    
 
    Retrieves fragment lengths grouped in bins given a BAM/SAM/CRAM/Fragment file.
    
-
    finaletoolkit frag-length-bins [-h] [-c CONTIG] [-S START] [-p {midpoint,any}] [-E STOP] [--bin-size BIN_SIZE] [-o OUTPUT_FILE]
-                               [--contig-by-contig] [--histogram] [-q QUALITY_THRESHOLD] [-v]
+
    finaletoolkit frag-length-bins [-h] [-c CONTIG] [-S START] [-p {midpoint,any}] [-E STOP]
+                               [--bin-size BIN_SIZE] [-o OUTPUT_FILE] [--contig-by-contig]
+                               [--histogram] [-q QUALITY_THRESHOLD] [-v]
                                input_file
 
    
 
    
@@ -491,7 +494,8 @@ 
    Named Arguments
 
    frag-length-intervals#
    
 
    Retrieves fragment length summary statistics over intervals defined in a BED file based on alignment data from a BAM/SAM/CRAM/Fragment file.
    
-
    finaletoolkit frag-length-intervals [-h] [-p {midpoint,any}] [-o OUTPUT_FILE] [-q QUALITY_THRESHOLD] [-w WORKERS] [-v]
+
    finaletoolkit frag-length-intervals [-h] [-p {midpoint,any}] [-o OUTPUT_FILE]
+                                    [-q QUALITY_THRESHOLD] [-w WORKERS] [-v]
                                     input_file interval_file
 
    
 
    
@@ -536,8 +540,8 @@ 
    Named Arguments
 
    cleavage-profile#
    
 
    Calculates cleavage proportion over intervals defined in a BED file based on alignment data from a BAM/SAM/CRAM/Fragment file.
    
-
    finaletoolkit cleavage-profile [-h] [-o OUTPUT_FILE] [-lo FRACTION_LOW] [-hi FRACTION_HIGH] [-q QUALITY_THRESHOLD] [-l LEFT] [-r RIGHT]
-                               [-w WORKERS] [-v]
+
    finaletoolkit cleavage-profile [-h] [-o OUTPUT_FILE] [-lo FRACTION_LOW] [-hi FRACTION_HIGH]
+                               [-q QUALITY_THRESHOLD] [-l LEFT] [-r RIGHT] [-w WORKERS] [-v]
                                input_file interval_file
 
    
 
    
@@ -593,8 +597,9 @@ 
    Named Arguments
 
    wps#
    
 
    Calculates Windowed Protection Score (WPS) over intervals defined in a BED file based on alignment data from a BAM/SAM/CRAM/Fragment file.
    
-
    finaletoolkit wps [-h] [-o OUTPUT_FILE] [-i INTERVAL_SIZE] [-W WINDOW_SIZE] [-lo FRACTION_LOW] [-hi FRACTION_HIGH] [-q QUALITY_THRESHOLD]
-                  [-w WORKERS] [-v]
+
    finaletoolkit wps [-h] [-o OUTPUT_FILE] [-i INTERVAL_SIZE] [-W WINDOW_SIZE]
+                  [-lo FRACTION_LOW] [-hi FRACTION_HIGH] [-q QUALITY_THRESHOLD] [-w WORKERS]
+                  [-v]
                   input_file site_bed
 
    
 
    
@@ -650,8 +655,9 @@ 
    Named Arguments
 
    adjust-wps#
    
 
    Adjusts raw Windowed Protection Score (WPS) by applying a median filter and Savitsky-Golay filter.
    
-
    finaletoolkit adjust-wps [-h] [-o OUTPUT_FILE] [-i INTERVAL_SIZE] [-m MEDIAN_WINDOW_SIZE] [-s SAVGOL_WINDOW_SIZE] [-p SAVGOL_POLY_DEG]
-                         [-w WORKERS] [--mean] [--subtract-edges] [-v]
+
    finaletoolkit adjust-wps [-h] [-o OUTPUT_FILE] [-i INTERVAL_SIZE] [-m MEDIAN_WINDOW_SIZE]
+                         [-s SAVGOL_WINDOW_SIZE] [-p SAVGOL_POLY_DEG] [-w WORKERS] [--mean]
+                         [--subtract-edges] [-v]
                          input_file interval_file genome_file
 
    
 
    
@@ -713,8 +719,8 @@ 
    Named Arguments
 
    delfi#
    
 
    Calculates DELFI featrues over genome, returning information about (GC-corrected) short fragments, long fragments, DELFI ratio, and total fragments. NOTE: Due to some ad hoc implementation details, currently the only accepted reference genome is hg19.
    
-
    finaletoolkit delfi [-h] [-b BLACKLIST_FILE] [-g GAP_FILE] [-o OUTPUT_FILE] [-W WINDOW_SIZE] [-gc] [-m] [-q QUALITY_THRESHOLD] [-w WORKERS]
-                    [-v]
+
    finaletoolkit delfi [-h] [-b BLACKLIST_FILE] [-g GAP_FILE] [-o OUTPUT_FILE] [-G] [-R] [-M]
+                    [-q QUALITY_THRESHOLD] [-w WORKERS] [-v]
                     input_file autosomes reference_file bins_file
 
    
 
    
@@ -738,29 +744,29 @@ 
    Positional Arguments
 
    Named Arguments#
    
 
    
-
    -b, --blacklist_file
    
+
    -b, --blacklist-file
    
 
    BED file containing regions to ignore when calculating DELFI.
    
 
    
-
    -g, --gap_file
    
+
    -g, --gap-file
    
 
    BED4 format file containing columns for “chrom”, “start”, “stop”, and “type”. The “type” column should denote whether the entry corresponds to a “centromere”, “telomere”, or “short arm”, and entries not falling into these categories are ignored. This information corresponds to the “gap” track for hg19 in the UCSC Genome Browser.
    
 
    
-
    -o, --output_file
    
+
    -o, --output-file
    
 
    BED, bed.gz, TSV, or CSV file to write DELFI data to. If “-”, writes to stdout.
    
 
    Default: “-”
    
 
    
-
    -W, --window_size
    
-
    Currently unused.
    
-
    Default: 5000000
    
+
    -G, --no-gc-correct
    
+
    Skip GC correction.
    
+
    Default: True
    
 
    
-
    -gc, --gc_correct
    
-
    Indicates whether to apply GC correction.
    
-
    Default: False
    
+
    -R, --keep-nocov
    
+
    Skip removal two regions in hg19 with no coverage. Use this flag when not using hg19 human reference genome.
    
+
    Default: True
    
 
    
-
    -m, --merge_bins
    
-
    Indicates whether to merge bins to 5Mb size.
    
-
    Default: False
    
+
    -M, --no-merge-bins
    
+
    Keep 100kb bins and do not merge to 5Mb size.
    
+
    Default: True
    
 
    
-
    -q, --quality_threshold
    
+
    -q, --quality-threshold
    
 
    Minimum mapping quality threshold.
    
 
    Default: 30
    
 
    
@@ -778,7 +784,8 @@ 
    Named Arguments
 
    delfi-gc-correct#
    
 
    Performs gc-correction on raw delfi data.
    
-
    finaletoolkit delfi-gc-correct [-h] [-o OUTPUT_FILE] [--header-lines HEADER_LINES] [-v] input_file
+
    finaletoolkit delfi-gc-correct [-h] [-o OUTPUT_FILE] [--header-lines HEADER_LINES] [-v]
+                               input_file
 
    
 
    
 
    
@@ -809,7 +816,9 @@ 
    Named Arguments
 
    end-motifs#
    
 
    Measures frequency of k-mer 5’ end motifs.
    
-
    finaletoolkit end-motifs [-h] [-k K] [-o OUTPUT_FILE] [-q QUALITY_THRESHOLD] [-w WORKERS] [-v] input_file refseq_file
+
    finaletoolkit end-motifs [-h] [-k K] [-o OUTPUT_FILE] [-q QUALITY_THRESHOLD] [-w WORKERS]
+                         [-v]
+                         input_file refseq_file
 
    
 
    
 
    
@@ -852,8 +861,8 @@ 
    Named Arguments
 
    interval-end-motifs#
    
 
    Measures frequency of k-mer 5’ end motifs in each region specified in a BED file and writes data into a table.
    
-
    finaletoolkit interval-end-motifs [-h] [-k K] [-lo FRACTION_LOW] [-hi FRACTION_HIGH] [-o OUTPUT_FILE] [-q QUALITY_THRESHOLD] [-w WORKERS]
-                                  [-v]
+
    finaletoolkit interval-end-motifs [-h] [-k K] [-lo FRACTION_LOW] [-hi FRACTION_HIGH]
+                                  [-o OUTPUT_FILE] [-q QUALITY_THRESHOLD] [-w WORKERS] [-v]
                                   input_file refseq_file intervals
 
    
 
    
@@ -966,8 +975,8 @@ 
    Named Arguments
 
    filter-bam#
    
 
    Filters a BAM file so that all reads are in mapped pairs, exceed a certain MAPQ, are not flagged for quality, are read1, are not secondary or supplementary alignments, and are on the same reference sequence as the mate.
    
-
    finaletoolkit filter-bam [-h] [-r REGION_FILE] [-o OUTPUT_FILE] [-q QUALITY_THRESHOLD] [-hi FRACTION_HIGH] [-lo FRACTION_LOW] [-w WORKERS]
-                         [-v]
+
    finaletoolkit filter-bam [-h] [-r REGION_FILE] [-o OUTPUT_FILE] [-q QUALITY_THRESHOLD]
+                         [-hi FRACTION_HIGH] [-lo FRACTION_LOW] [-w WORKERS] [-v]
                          input_file
 
    
 
    
@@ -1012,7 +1021,8 @@ 
    Named Arguments
 
    agg-bw#
    
 
    Aggregates a bigWig signal over constant-length intervals defined in a BED file.
    
-
    finaletoolkit agg-bw [-h] [-o OUTPUT_FILE] [-m MEDIAN_WINDOW_SIZE] [-v] input_file interval_file
+
    finaletoolkit agg-bw [-h] [-o OUTPUT_FILE] [-m MEDIAN_WINDOW_SIZE] [-v]
+                     input_file interval_file
 
    
 
    
 
    
diff --git a/searchindex.js b/searchindex.js
index 9012b64..83ff7da 100644
--- a/searchindex.js
+++ b/searchindex.js
@@ -1 +1 @@
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"cleavage-profile"]], "DELFI": [[2, "delfi"], [10, "delfi"]], "End-Motifs": [[3, "end-motifs"]], "Frag File Utilities": [[4, "frag-file-utilities"]], "Genome Utilities": [[5, "genome-utilities"]], "API": [[6, "api"]], "Window Protection Score (WPS)": [[7, "window-protection-score-wps"]], "CLI": [[8, "cli"]], "Named Arguments": [[8, "named-arguments"], [8, "named-arguments_repeat1"], [8, "named-arguments_repeat2"], [8, "named-arguments_repeat3"], [8, "named-arguments_repeat4"], [8, "named-arguments_repeat5"], [8, "named-arguments_repeat6"], [8, "named-arguments_repeat7"], [8, "named-arguments_repeat8"], [8, "named-arguments_repeat9"], [8, "named-arguments_repeat10"], [8, "named-arguments_repeat11"], [8, "named-arguments_repeat12"], [8, "named-arguments_repeat13"], [8, "named-arguments_repeat14"]], "Sub-commands": [[8, "Sub-commands"]], "coverage": [[8, "coverage"]], "Positional Arguments": [[8, "positional-arguments"], [8, "positional-arguments_repeat1"], [8, "positional-arguments_repeat2"], [8, "positional-arguments_repeat3"], [8, "positional-arguments_repeat4"], [8, "positional-arguments_repeat5"], [8, "positional-arguments_repeat6"], [8, "positional-arguments_repeat7"], [8, "positional-arguments_repeat8"], [8, "positional-arguments_repeat9"], [8, "positional-arguments_repeat10"], [8, "positional-arguments_repeat11"], [8, "positional-arguments_repeat12"], [8, "positional-arguments_repeat13"], [8, "positional-arguments_repeat14"]], "frag-length-bins": [[8, "frag-length-bins"]], "frag-length-intervals": [[8, "frag-length-intervals"]], "cleavage-profile": [[8, "cleavage-profile"]], "wps": [[8, "wps"]], "adjust-wps": [[8, "adjust-wps"]], "delfi": [[8, "delfi"]], "delfi-gc-correct": [[8, "delfi-gc-correct"]], "end-motifs": [[8, "end-motifs"]], "interval-end-motifs": [[8, "interval-end-motifs"]], "mds": [[8, "mds"]], "interval-mds": [[8, "interval-mds"]], "filter-bam": [[8, "filter-bam"]], "agg-bw": [[8, "agg-bw"]], "gap-bed": [[8, "gap-bed"]], "FinaleToolkit Documentation": [[9, "finaletoolkit-documentation"]], "Features": [[10, "features"]], "Fragment Length": [[10, "fragment-length"]], "Fragment Coverage": [[10, "fragment-coverage"]], "Windowed Protection Score (WPS)": [[10, "windowed-protection-score-wps"]], "End Motifs": [[10, "end-motifs"]], "Motif Diversity Score (MDS)": [[10, "motif-diversity-score-mds"]], "Help": [[11, "help"]], "User Guide": [[12, "user-guide"]], "Input Data": [[13, "input-data"]], "SAM": [[13, "sam"]], "BAM": [[13, "bam"]], "CRAM": [[13, "cram"]], "Fragment File": [[13, "fragment-file"]], "Installation": [[14, "installation"], [14, "id1"]], "Prerequisites": [[14, "prerequisites"]], "Errors": [[14, "errors"]], "Intersect Policy": [[15, "intersect-policy"]], "Midpoint": [[15, "midpoint"]], "Any": [[15, "any"]], "Quickstart": [[16, "quickstart"]], "Getting Started": [[16, "getting-started"]], "Importing Modules": [[16, "importing-modules"]], "Structure": [[17, "structure"]], "Introduction": [[18, "introduction"]], "FinaleToolkit": [[19, "finaletoolkit"]], "About": [[19, "about"]], "Documentation": [[19, "documentation"]], "Citations": [[19, "citations"]], "Contact": [[19, "contact"]], "License": [[19, "license"]]}, "indexentries": {"coverage() (in module finaletoolkit.frag)": [[0, "finaletoolkit.frag.coverage"]], "frag_length() (in module finaletoolkit.frag)": [[0, "finaletoolkit.frag.frag_length"]], "frag_length_bins() (in module finaletoolkit.frag)": [[0, "finaletoolkit.frag.frag_length_bins"]], "cleavage_profile() (in module finaletoolkit.frag)": [[1, "finaletoolkit.frag.cleavage_profile"]], "delfi() (in module finaletoolkit.frag)": [[2, "finaletoolkit.frag.delfi"]], "delfi_gc_correct() (in module finaletoolkit.frag)": [[2, "finaletoolkit.frag.delfi_gc_correct"]], "delfi_merge_bins() (in module finaletoolkit.frag)": [[2, "finaletoolkit.frag.delfi_merge_bins"]], "endmotiffreqs (class in finaletoolkit.frag)": [[3, "finaletoolkit.frag.EndMotifFreqs"]], "endmotifsintervals (class in finaletoolkit.frag)": [[3, "finaletoolkit.frag.EndMotifsIntervals"]], "end_motifs() (in module finaletoolkit.frag)": [[3, "finaletoolkit.frag.end_motifs"]], "freq() (finaletoolkit.frag.endmotifsintervals method)": [[3, "finaletoolkit.frag.EndMotifsIntervals.freq"]], "from_file() (finaletoolkit.frag.endmotiffreqs class method)": [[3, "finaletoolkit.frag.EndMotifFreqs.from_file"]], "from_file() (finaletoolkit.frag.endmotifsintervals class method)": [[3, "finaletoolkit.frag.EndMotifsIntervals.from_file"]], "interval_end_motifs() (in module finaletoolkit.frag)": [[3, "finaletoolkit.frag.interval_end_motifs"]], "mds_bed() (finaletoolkit.frag.endmotifsintervals method)": [[3, "finaletoolkit.frag.EndMotifsIntervals.mds_bed"]], "motif_diversity_score() (finaletoolkit.frag.endmotiffreqs method)": [[3, "finaletoolkit.frag.EndMotifFreqs.motif_diversity_score"]], "motif_diversity_score() (finaletoolkit.frag.endmotifsintervals method)": [[3, "finaletoolkit.frag.EndMotifsIntervals.motif_diversity_score"]], "region_end_motifs() (in module finaletoolkit.frag)": [[3, "finaletoolkit.frag.region_end_motifs"]], "to_bed() (finaletoolkit.frag.endmotifsintervals method)": [[3, "finaletoolkit.frag.EndMotifsIntervals.to_bed"]], "to_bedgraph() (finaletoolkit.frag.endmotifsintervals method)": [[3, "finaletoolkit.frag.EndMotifsIntervals.to_bedgraph"]], "to_tsv() (finaletoolkit.frag.endmotiffreqs method)": [[3, "finaletoolkit.frag.EndMotifFreqs.to_tsv"]], "to_tsv() (finaletoolkit.frag.endmotifsintervals method)": [[3, "finaletoolkit.frag.EndMotifsIntervals.to_tsv"]], "agg_bw() (in module finaletoolkit.utils)": [[4, "finaletoolkit.utils.agg_bw"]], "chrom_sizes_to_dict() (in module finaletoolkit.utils)": [[4, "finaletoolkit.utils.chrom_sizes_to_dict"]], "chrom_sizes_to_list() (in module finaletoolkit.utils)": [[4, "finaletoolkit.utils.chrom_sizes_to_list"]], "filter_bam() (in module finaletoolkit.utils)": [[4, "finaletoolkit.utils.filter_bam"]], "frag_array() (in module finaletoolkit.utils)": [[4, "finaletoolkit.utils.frag_array"]], "frag_generator() (in module finaletoolkit.utils)": [[4, "finaletoolkit.utils.frag_generator"]], "low_quality_read_pairs() (in module finaletoolkit.utils)": [[4, "finaletoolkit.utils.low_quality_read_pairs"]], "overlaps() (in module finaletoolkit.utils)": [[4, "finaletoolkit.utils.overlaps"]], "contiggaps (class in finaletoolkit.genome)": [[5, "finaletoolkit.genome.ContigGaps"]], "genomegaps (class in finaletoolkit.genome)": [[5, "finaletoolkit.genome.GenomeGaps"]], "b37() (finaletoolkit.genome.genomegaps class method)": [[5, "finaletoolkit.genome.GenomeGaps.b37"]], "b37_gap_bed() (in module finaletoolkit.genome)": [[5, "finaletoolkit.genome.b37_gap_bed"]], "get_arm() (finaletoolkit.genome.contiggaps method)": [[5, "finaletoolkit.genome.ContigGaps.get_arm"]], "get_arm() (finaletoolkit.genome.genomegaps method)": [[5, "finaletoolkit.genome.GenomeGaps.get_arm"]], "get_contig_gaps() (finaletoolkit.genome.genomegaps method)": [[5, "finaletoolkit.genome.GenomeGaps.get_contig_gaps"]], "hg38() (finaletoolkit.genome.genomegaps class method)": [[5, "finaletoolkit.genome.GenomeGaps.hg38"]], "in_gap() (finaletoolkit.genome.contiggaps method)": [[5, "finaletoolkit.genome.ContigGaps.in_gap"]], "in_tcmere() (finaletoolkit.genome.contiggaps method)": [[5, "finaletoolkit.genome.ContigGaps.in_tcmere"]], "in_tcmere() (finaletoolkit.genome.genomegaps method)": [[5, "finaletoolkit.genome.GenomeGaps.in_tcmere"]], "overlaps_gap() (finaletoolkit.genome.genomegaps method)": [[5, "finaletoolkit.genome.GenomeGaps.overlaps_gap"]], "to_bed() (finaletoolkit.genome.genomegaps method)": [[5, "finaletoolkit.genome.GenomeGaps.to_bed"]], "ucsc_hg19() (finaletoolkit.genome.genomegaps class method)": [[5, "finaletoolkit.genome.GenomeGaps.ucsc_hg19"]], "ucsc_hg19_gap_bed() (in module finaletoolkit.genome)": [[5, "finaletoolkit.genome.ucsc_hg19_gap_bed"]], "ucsc_hg38_gap_bed() (in module finaletoolkit.genome)": [[5, "finaletoolkit.genome.ucsc_hg38_gap_bed"]], "adjust_wps() (in module finaletoolkit.frag)": [[7, "finaletoolkit.frag.adjust_wps"]], "multi_wps() (in module finaletoolkit.frag)": [[7, "finaletoolkit.frag.multi_wps"]], "wps() (in module finaletoolkit.frag)": [[7, "finaletoolkit.frag.wps"]]}})
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    Basic Features#
    
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-finaletoolkit.frag.coverage(input_file: str | TabixFile | AlignmentFile | Path, interval_file: str, output_file: str, scale_factor: float = 1000000.0, intersect_policy: str = 'midpoint', quality_threshold: int = 30, workers: int = 1, verbose: bool | int = False) → Iterable[tuple[str, int, int, str, float]]#
    
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    Return estimated fragment coverage over intervals specified in
-intervals. Fragments are read from input_file which may be
-a SAM, BAM, CRAM, or Frag.gz file. Uses an algorithm where the midpoints of
-fragments are calculated and coverage is tabulated from the
-midpoints that fall into the specified region. Not suitable for
-fragments of size approaching interval size.
    
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    • input_file (str or pysam.AlignmentFile) – SAM, BAM, CRAM, or Frag.gz file containing paired-end fragment
-reads or its path. AlignmentFile must be opened in read mode.
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-statistics.
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-results will be printed to stdout.
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      • 
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    • intersect_policy (str, optional) – Specifies how to determine whether fragments are in interval.
-‘midpoint’ (default) calculates the central coordinate of each fragment
-and only selects the fragment if the midpoint is in the
-interval. ‘any’ includes fragments with any overlap with the
-interval.
      • 
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    • quality_threshold (int, optional) – Minimum MAPQ. Default is 30.
      • 
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-of memory.
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      • 
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-that are above the quality threshold and are proper-paired reads.
    
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    Parameters:
    
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-its path. AlignmentFile must be opened in read mode.
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      • 
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-given interval. Default is “midpoint”. Policies include:
-- midpoint: the average of end coordinates of a fragment lies
-in the interval.
-- any: any part of the fragment is in the interval.
      • 
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-specified.
    
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-
    Takes input_file, computes frag lengths of fragments and returns
-two arrays containing bins and counts by size. Optionally prints
-data to output as a tab delimited table or histogram.
    
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-given interval. Default is “midpoint”. Policies include:
-- midpoint: the average of end coordinates of a fragment lies
-in the interval.
-- any: any part of the fragment is in the interval.
      • 
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-finaletoolkit.frag.cleavage_profile(input_file: str, chrom_size: int, contig: str, start: int, stop: int, left: int = 0, right: int = 0, fraction_low: int = 1, fraction_high: int = 10000000, quality_threshold: int = 30, verbose: bool | int = 0) → ndarray#
    
-
    Cleavage profile calculated over a single interval.
    
-
    
-
    Parameters:
    
-
      
-
    • input_file (str) – SAM, BAM, CRAM, or FRAG file with fragment information.
      • 
-
    • chrom_size (int) – length of contig.
      • 
-
    • contig (str) – Chromosome or contig
      • 
-
    • start (int) – 0-based start coordinate
      • 
-
    • stop (int) – 1-based end coordinate
      • 
-
    • left (int) – Amount to subtract from start coordinate. Useful if only given
-coordinates of CpG.
      • 
-
    • right (int) – Amount to add to stop coordinate.
      • 
-
    • fraction_low (int) – Minimum fragment size to include
      • 
-
    • fraction_high (int) – Maximum fragment size to include
      • 
-
    • quality_threshold (int) – Minimum MAPQ
      • 
-
    • verbose (bool or in)
      • 
-
    
-
    
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    Returns:
    
-
    cleavage_proportions – Array of cleavage proportions over given interval.
    
-
    
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    Return type:
    
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diff --git a/source/api_reference/delfi.html b/source/api_reference/delfi.html
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    DELFI#
    
-
    
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-finaletoolkit.frag.delfi(input_file: str, autosomes: str, bins_file: str, reference_file: str, blacklist_file: str = None, gap_file: Union(str, GenomeGaps) = None, output_file: str = None, gc_correct: bool = True, merge_bins: bool = True, window_size: int = 5000000, subsample_coverage: float = 2, quality_threshold: int = 30, workers: int = 1, preprocessing: bool = True, verbose: int | bool = False) → pandas.DataFrame#
    
-
    A function that replicates the methodology of Christiano et al
-(2019).
    
-
    
-
    Parameters:
    
-
      
-
    • input_file (str) – Path string pointing to a bam file containing PE
-fragment reads.
      • 
-
    • autosomes (str) – Path string to a .genome file containing only autosomal
-chromosomes
      • 
-
    • bins_file (str) – Path string to a BED file containing 100kb bins for reference
-genome of choice. Cristiano et al uses
      • 
-
    • reference_file (str) – Path string to .2bit file.
      • 
-
    • blacklist_file (str) – Path string to BED file containing genome blacklist.
      • 
-
    • gap_file (str) – Path string to a BED4+ file where each interval is a centromere
-or telomere. A bed file can be used only if the fourth field
-for each entry corresponding to a telomere or centromere is
-labled “telomere” or “centromere, respectively.
      • 
-
    • output_file (str, optional) – Path to output tsv.
      • 
-
    • window_size (int) – Size of non-overlapping windows to cover genome. Default is
-5 megabases.
      • 
-
    • subsample_coverage (int, optional) – The depth at which to subsample the input_bam. Default is 2.
      • 
-
    • workers (int, optional) – Number of worker processes to use. Default is 1.
      • 
-
    • preprocessing (bool, optional) – Christiano et al (2019)
      • 
-
    • verbose (int or bool, optional) – Determines how many print statements and loading bars appear in
-stdout. Default is False.
      • 
-
    
-
    
-
    
-
    
-
-
    
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-finaletoolkit.frag.delfi_gc_correct(windows: DataFrame, alpha: float = 0.75, it: int = 8, verbose: bool = False)#
    
-
    Helper function that takes window data and performs GC adjustment.
    
-
    
-
-
    
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-finaletoolkit.frag.delfi_merge_bins(hundred_kb_bins: DataFrame, gc_corrected: bool = True, add_chr: bool = False, verbose: bool = False)#
    
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diff --git a/source/api_reference/endmotifs.html b/source/api_reference/endmotifs.html
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    End-Motifs#
    
-
    
-
    
-class finaletoolkit.frag.EndMotifFreqs(kmer_frequencies: Iterable[tuple[str, float]], k: int, quality_threshold: int = 20)#
    
-
    Class that stores frequencies of end-motif k-mer frequencies and
-contains methods to manipulate this data.
    
-
    
-
    Parameters:
    
-
      
-
    • kmer_frequencies (Iterable) – A Iterable of tuples, each containing a str representing a k-mer
-and a float representing its frequency
      • 
-
    • k (int) – Size of k-mers
      • 
-
    • quality_threshold (int, optional) – Minimum mapping quality used. Default is 30.
      • 
-
    
-
    
-
    
-
    
-
    
-classmethod from_file(file_path: str | Path, quality_threshold: int, sep: str = '\t', header: int = 0) → EndMotifFreqs#
    
-
    Reads kmer frequency from a two-column tab-delimited file.
    
-
    
-
    Parameters:
    
-
      
-
    • file_path (str) – Path string containing path to file.
      • 
-
    • sep (str, optional) – Delimiter used in file.
      • 
-
    • header (int, optional) – Number of lines to ignore at the head of the file.
      • 
-
    
-
    
-
    Returns:
    
-
    kmer_freqs
    
-
    
-
    Return type:
    
-
    EndMotifFreqs
    
-
    
-
    
-
    
-
-
    
-
    
-motif_diversity_score() → float#
    
-
    Calculates a motif diversity score (MDS) using normalized
-Shannon entropy as described by Jiang et al (2020). This
-function is generalized for any k instead of just 4-mers.
    
-
    
-
-
    
-
    
-to_tsv(output_file: str | Path, sep: str = '\t')#
    
-
    Prints k-mer frequencies to a tsv
    
-
    
-
-
    
-
-
    
-
    
-class finaletoolkit.frag.EndMotifsIntervals(intervals: Iterable[tuple[tuple, dict]], k: int, quality_threshold: int = 20)#
    
-
    Class that stores frequencies of end-motif k-mers over
-user-specified intervals and contains methods to manipulate this
-data.
    
-
    
-
    Parameters:
    
-
      
-
    • intervals (Iterable) – A collection of tuples, each containing a tuple representing
-a genomic interval (chrom, 0-based start, 1-based stop) and a
-dict that maps kmers to frequencies in the interval.
      • 
-
    • k (int) – Size of k-mers
      • 
-
    • quality_threshold (int, optional) – Minimum mapping quality used. Default is 30.
      • 
-
    
-
    
-
    
-
    
-
    
-freq(kmer: str) → list[tuple[str, int, int, float]]#
    
-
    Returns a list of intervals and associated frquency for given
-kmer. Results are in the form (chrom, 0-based start, 1-based
-stop, frequency).
    
-
    
-
-
    
-
    
-classmethod from_file(file_path: str, quality_threshold: int, sep: str = ',') → EndMotifFreqs#
    
-
    Reads kmer frequency from a tab-delimited file. Expected columns
-are contig, start, stop, name, count, *kmers. Because
-exporting to file includes an option to turn counts to a fraction,
-this doesn’t perfectly correspond to replicating the other file.
    
-
    
-
    Parameters:
    
-
      
-
    • file_path (str) – Path string containing path to file.
      • 
-
    • quality_threshold (int) – MAPQ filter used. Only used for some calculations.
      • 
-
    • sep (str, optional) – Delimiter used in file.
      • 
-
    
-
    
-
    Returns:
    
-
    kmer_freqs
    
-
    
-
    Return type:
    
-
    EndMotifFreqs
    
-
    
-
    
-
    
-
-
    
-
    
-mds_bed(output_file: str | Path, sep: str = '\t')#
    
-
    Writes MDS for each interval to a bed/bedgraph file.
    
-
    
-
-
    
-
    
-motif_diversity_score() → list[tuple[tuple, float]]#
    
-
    Calculates a motif diversity score (MDS) for each interval using
-normalized Shannon entropy as described by Jiang et al (2020). This
-function is generalized for any k instead of just 4-mers.
    
-
    
-
-
    
-
    
-to_bed(kmer: str, output_file: str | Path, calc_freq: bool = True, sep: str = '\t')#
    
-
    Take frequency of specified kmer and writes to BED.
    
-
    
-
    Parameters:
    
-
      
-
    • output_file (str) – File to write frequencies to.
      • 
-
    • calc_freq (bool, optional) – Calculates frequency of motifs if true. Otherwise, writes counts
-for each motif. Default is true.
      • 
-
    • sep (str, optional) – Separator for table. Tab-separated by default.
      • 
-
    
-
    
-
    
-
    
-
-
    
-
    
-to_bedgraph(kmer: str, output_file: str | Path, calc_freq: bool = True, sep: str = '\t')#
    
-
    Take frequency of specified kmer and writes to bedgraph.
    
-
    
-
    Parameters:
    
-
      
-
    • output_file (str) – File to write frequencies to.
      • 
-
    • calc_freq (bool, optional) – Calculates frequency of motifs if true. Otherwise, writes counts
-for each motif. Default is true.
      • 
-
    • sep (str, optional) – Separator for table. Tab-separated by default.
      • 
-
    
-
    
-
    
-
    
-
-
    
-
    
-to_tsv(output_file: str | Path, calc_freq: bool = True, sep: str = '\t')#
    
-
    Writes all intervals and associated frquencies to file. Columns
-are contig, start, stop, name, count, *kmers.
    
-
    
-
    Parameters:
    
-
      
-
    • output_file (str) – File to write frequencies to.
      • 
-
    • calc_freq (bool, optional) – Calculates frequency of motifs if true. Otherwise, writes counts
-for each motif. Default is true.
      • 
-
    • sep (str, optional) – Separator for table. Tab-separated by default.
      • 
-
    
-
    
-
    
-
    
-
-
    
-
-
    
-
    
-finaletoolkit.frag.region_end_motifs(input_file: str, contig: str, start: int, stop: int, refseq_file: str | Path, k: int = 4, fraction_low: int = 10, fraction_high: int = 600, both_strands: bool = True, output_file: None | str = None, quality_threshold: int = 20, verbose: bool | int = False) → dict#
    
-
    Function that reads fragments in the specified region from a BAM,
-SAM, or tabix indexed file and returns the 5’ k-mer (default is
-4-mer) end motif counts as a dictionary. This function
-reproduces the methodology of Zhou et al (2023).
    
-
    
-
    Parameters:
    
-
      
-
    • input_file (str) – Path of SAM, BAM, CRAM, or Frag.gz containing pair-end reads.
      • 
-
    • contig (str) – Name of contig or chromosome for region.
      • 
-
    • start (int) – 0-based start coordinate.
      • 
-
    • stop (int) – 1-based end coordinate.
      • 
-
    • refseq_file (str or Path) – 2bit file with reference sequence input_file was aligned to.
      • 
-
    • k (int, optional) – Length of end motif kmer. Default is 4.
      • 
-
    • fraction_low (int, optional) – Minimum fragment length.
      • 
-
    • fraction_high (int, optional) – Maximum fragment length.
      • 
-
    • both_strands (bool, optional) – Choose whether to use forward 5’ ends only or use 5’ ends for
-both ends of PE reads.
      • 
-
    • output_file (None or str, optional)
      • 
-
    • quality_threshold (int, optional)
      • 
-
    • verbose (bool or int, optional)
      • 
-
    
-
    
-
    Returns:
    
-
    end_motif_freq
    
-
    
-
    Return type:
    
-
    dict
    
-
    
-
    
-
    
-
-
    
-
    
-finaletoolkit.frag.end_motifs(input_file: str, refseq_file: str | Path, k: int = 4, fraction_low: int = 10, fraction_high: int = 600, both_strands: bool = False, output_file: None | str = None, quality_threshold: int = 30, workers: int = 1, verbose: bool | int = False) → EndMotifFreqs#
    
-
    Function that reads fragments from a BAM, SAM, or tabix indexed
-file and returns the 5’ k-mer (default is 4-mer) end motif
-frequencies as a dictionary. Optionally writes data to a tsv. This
-function reproduces the methodology of Zhou et al (2023).
    
-
    
-
    Parameters:
    
-
      
-
    • input_file (str) – SAM, BAM, CRAM, or Frag.gz file with paired-end reads.
      • 
-
    • refseq_file (str or Path) – 2bit file with sequence of reference genome input_file is
-aligned to.
      • 
-
    • k (int, optional) – Length of end motif kmer. Default is 4.
      • 
-
    • output_file (None or str, optional) – File path to write results to. Either tsv or csv.
      • 
-
    • quality_threshold (int, optional) – Minimum MAPQ to filter.
      • 
-
    • workers (int, optional) – Number of worker processes.
      • 
-
    • verbose (bool or int, optional)
      • 
-
    
-
    
-
    Returns:
    
-
    end_motif_freq
    
-
    
-
    Return type:
    
-
    EndMotifFreqs
    
-
    
-
    
-
    
-
-
    
-
    
-finaletoolkit.frag.interval_end_motifs(input_file: str, refseq_file: str | Path, intervals: str | Iterable[tuple[str, int, int, str]], k: int = 4, fraction_low: int = 10, fraction_high: int = 600, both_strands: bool = True, output_file: None | str = None, quality_threshold: int = 30, workers: int = 1, verbose: bool | int = False) → EndMotifsIntervals#
    
-
    Function that reads fragments from a BAM, SAM, or tabix indexed
-file and user-specified intervals and returns the 5’ k-mer
-(default is 4-mer) end motif. Optionally writes data to a tsv.
    
-
    
-
    Parameters:
    
-
      
-
    • input_file (str) – Path of SAM, BAM, CRAM, or Frag.gz containing pair-end reads.
      • 
-
    • refseq_file (str or Path) – Path of 2bit file for reference genome that reads are aligned to.
      • 
-
    • intervals (str or tuple) – Path of BED file containing intervals or list of tuples
-(chrom, start, stop, name).
      • 
-
    • k (int, optional) – Length of end motif kmer. Default is 4.
      • 
-
    • output_file (None or str, optional) – File path to write results to. Either tsv or csv.
      • 
-
    • quality_threshold (int, optional) – Minimum MAPQ to filter.
      • 
-
    • workers (int, optional) – Number of worker processes.
      • 
-
    • verbose (bool or int, optional)
      • 
-
    
-
    
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    Returns:
    
-
    end_motif_freq
    
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    Return type:
    
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    EndMotifIntervals
    
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diff --git a/source/api_reference/fragfile.html b/source/api_reference/fragfile.html
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    Frag File Utilities#
    
-
    
-
    
-finaletoolkit.utils.filter_bam(input_file: str, region_file: str | None = None, output_file: str | None = None, max_length: int | None = None, min_length: int | None = None, quality_threshold: int = 30, workers: int = 1, verbose: bool = False)#
    
-
    Accepts the path to a BAM file and creates a bam file where all
-reads are read1 in a proper pair, exceed the specified quality
-threshold, do not intersect a region in the given blacklist
-file, and intersects with a region in the region bed.
    
-
    
-
    Parameters:
    
-
      
-
    • input_bam (str) – Path string or AlignmentFile pointing to the BAM file to be
-filtered.
      • 
-
    • region_file (str, option)
      • 
-
    • output_file (str, optional)
      • 
-
    • min_length (int, optional)
      • 
-
    • max_length (int, optional)
      • 
-
    • quality_threshold (int, optional)
      • 
-
    • workers (int, optional)
      • 
-
    • verbose (bool, optional)
      • 
-
    
-
    
-
    Returns:
    
-
    output_file
    
-
    
-
    Return type:
    
-
    str
    
-
    
-
    
-
    
-
-
    
-
    
-finaletoolkit.utils.agg_bw(input_file: str, interval_file: str, output_file: str, median_window_size: int = 0, mean: bool = False, strand_location: int = 5, verbose: bool = False)#
    
-
    Takes a BigWig and an interval BED and
-aggregates signal along the intervals.
    
-
    For aggregating WPS signals, note that the median filter trims the
-ends of each interval by half of the window size of the filter
-while adjusting data. There are two way this can be approached in
-aggregation:
    
-
    1. supply an interval file containing smaller intervals. e.g. if
-you used 5kb intervals for WPS and used a median filter window
-of 1kb, supply a BED file with 4kb windows to this function.
    
-
    2. provide the size of the median filter window in
-median_window_size along with the original intervals. e.g if
-5kb intervals were used for WPS and a 1kb median filter window
-was used, supply the 5kb bed file and median filter window size
-to this function.
    
-
    Do not do both of these at once.
    
-
    
-
    Parameters:
    
-
      
-
    • input_file (str)
      • 
-
    • interval_file (str)
      • 
-
    • output_file (str)
      • 
-
    • median_window_size (int, optional) – default is 0
      • 
-
    • mean (bool) – use mean instead
      • 
-
    • strand_location (int) – which column (starting at 0) of the interval file contains the
-strand. Default is 5.
      • 
-
    • verbose (int or bool, optional) – default is False
      • 
-
    
-
    
-
    Returns:
    
-
    agg_scores
    
-
    
-
    Return type:
    
-
    NDArray
    
-
    
-
    
-
    
-
-
    
-
    
-finaletoolkit.utils.chrom_sizes_to_list(chrom_sizes_file: str | Path) → list[tuple[str][int]]#
    
-
    Reads chromosome names and sizes from a CHROMSIZE file into a list.
    
-
    
-
    Parameters:
    
-
    chrom_sizes_file (str or Path) – Tab-delimited file with column for chrom names and column for
-chrom sizes.
    
-
    
-
    Returns:
    
-
    chrom names and sizes.
    
-
    
-
    Return type:
    
-
    list of string, int tuples
    
-
    
-
    
-
    
-
-
    
-
    
-finaletoolkit.utils.chrom_sizes_to_dict(chrom_sizes_file: str | Path) → list[tuple[str][int]]#
    
-
    Reads chromosome names and sizes from a CHROMSIZE file into a dict.
    
-
    
-
    Parameters:
    
-
    chrom_sizes_file (str or Path) – Tab-delimited file with column for chrom names and column for
-chrom sizes.
    
-
    
-
    Returns:
    
-
    Chrom names are keys and values are int chrom sizes.
    
-
    
-
    Return type:
    
-
    dict
    
-
    
-
    
-
    
-
-
    
-
    
-finaletoolkit.utils.frag_generator(input_file: str | pysam.AlignmentFile | pysam.TabixFile | Path, contig: str, quality_threshold: int = 30, start: int = None, stop: int = None, fraction_low: int = 120, fraction_high: int = 180, intersect_policy: str = 'midpoint', verbose: bool = False) → Generator[tuple]#
    
-
    Reads from BAM, SAM, or BED file and returns tuples containing
-contig (chromosome), start, stop (end), mapq, and strand for each fragment.
-Optionally may filter for mapq, size, and intersection with a region.
    
-
    
-
    Parameters:
    
-
      
-
    • input_file (str or AlignmentFile)
      • 
-
    • contig (str)
      • 
-
    • quality_threshold (int, optional)
      • 
-
    • start (int, optional)
      • 
-
    • stop (int, optional)
      • 
-
    • fraction_low (int, optional) – Specifies lowest fragment length included in array. Default is
-120, equivalent to long fraction.
      • 
-
    • fraction_high (int, optional) – Specifies highest fragment length included in array. Default is
-120, equivalent to long fraction.
      • 
-
    • intersect_policy (str, optional) – Specifies what policy is used to include fragments in the
-given interval. Default is “midpoint”. Policies include:
-- midpoint: the average of end coordinates of a fragment lies
-in the interval.
-- any: any part of the fragment is in the interval.
      • 
-
    • verbose (bool, optional)
      • 
-
    
-
    
-
    Returns:
    
-
    frag_ends – Generator that yields tuples containing the region covered by
-each fragment in input_file.
    
-
    
-
    Return type:
    
-
    Generator
    
-
    
-
    
-
    
-
-
    
-
    
-finaletoolkit.utils.frag_array(input_file: str | AlignmentFile | TabixFile | Path, contig: str, quality_threshold: int = 30, start: int | None = None, stop: int | None = None, fraction_low: int = 120, fraction_high: int = 180, intersect_policy: str = 'midpoint', verbose: bool = False) → ndarray[Any, dtype[_ScalarType_co]]#
    
-
    Reads from BAM, SAM, or BED file and returns a three column matrix
-with fragment start and stop positions and strand.
    
-
    
-
    Parameters:
    
-
      
-
    • input_file (str or AlignmentFile)
      • 
-
    • contig (str)
      • 
-
    • quality_threshold (int, optional)
      • 
-
    • start (int, optional)
      • 
-
    • stop (int, optional)
      • 
-
    • fraction_low (int, optional) – Specifies lowest fragment length included in array. Default is
-120, equivalent to long fraction.
      • 
-
    • fraction_high (int, optional) – Specifies highest fragment length included in array. Default is
-120, equivalent to long fraction.
-intersect_policy : str, optional
-Specifies what policy is used to include fragments in the
-given interval. Default is “midpoint”. Policies include:
-- midpoint: the average of end coordinates of a fragment lies
-in the interval.
-- any: any part of the fragment is in the interval.
      • 
-
    • verbose (bool, optional)
      • 
-
    
-
    
-
    Returns:
    
-
    frag_ends – ‘NDArray’ with shape (n, 3) where column 1 contains fragment
-start position and column 2 contains fragment stop position, and
-column3 is 1 of on the + strand and is 0 if on the - strand.
-If no fragments exist in the specified minimum-maximum interval,
-the returned ‘ndarray’ will have a shape of (0, 3)
    
-
    
-
    Return type:
    
-
    NDArray
    
-
    
-
    
-
    
-
-
    
-
    
-finaletoolkit.utils.low_quality_read_pairs(read, min_mapq=30)#
    
-
    Return True if the sequenced read described in read is not a
-properly paired read with a Phred score exceeding min_mapq. Based
-on epifluidlab/cofragr
-mmary_in_intervals.py
    
-
    Equivalent to -F 3852 -f 3
    
-
    
-
    Parameters:
    
-
      
-
    • read (pysam.AlignedSegment) – Sequenced read to check for quality, perfect pairing and if it
-is mapped.
      • 
-
    • min_mapq (int, optional) – Minimum Phred score for map quality of read. Defaults to 30.
      • 
-
    
-
    
-
    Returns:
    
-
    is_low_quality – True if read is low quality, unmapped, not properly paired.
    
-
    
-
    Return type:
    
-
    bool
    
-
    
-
    
-
    
-
-
    
-
    
-finaletoolkit.utils.overlaps(contigs_1: ndarray[Any, dtype[_ScalarType_co]], starts_1: ndarray[Any, dtype[_ScalarType_co]], stops_1: ndarray[Any, dtype[_ScalarType_co]], contigs_2: ndarray[Any, dtype[_ScalarType_co]], starts_2: ndarray[Any, dtype[_ScalarType_co]], stops_2: ndarray[Any, dtype[_ScalarType_co]]) → ndarray[Any, dtype[_ScalarType_co]]#
    
-
    Function that performs vectorized computation of overlaps. Returns
-an array of same shape as contig_1 that is true if the intervals
-for set 1 each have any overlap with an interval in set 2.
    
-
    
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-    Created using Sphinx 7.3.7.
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diff --git a/source/api_reference/genomeutils.html b/source/api_reference/genomeutils.html
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    Genome Utilities#
    
-
    
-
    
-class finaletoolkit.genome.GenomeGaps(gaps_bed: Path | str | None = None)#
    
-
    Reads telomere, centromere, and short_arm intervals from a bed file
-or generates these intervals from UCSC gap and centromere tracks for
-hg19 and hg38.
    
-
    
-
    
-classmethod b37()#
    
-
    Creates a GenomeGaps for the Broad Institute GRCh37 reference
-genome i.e b37. This reference genome is also based on GRCh37,
-but differs from the UCSC hg19 reference in a few ways,
-including the absence of the ‘chr’ prefix. We generate this
-GenomeGap using an ad hoc method where we take the UCSC hg19
-gap track and drop ‘chr’ from the chromosome names. Because
-there are other differences between hg19 and b37, this is not
-a perfect solution.
    
-
    
-
    Returns:
    
-
    gaps – GenomeGaps for the b37 reference genome.
    
-
    
-
    Return type:
    
-
    GenomeGaps
    
-
    
-
    
-
    
-
-
    
-
    
-get_arm(contig: str, start: int, stop: int) → str#
    
-
    Returns the chromosome arm the interval is in. If in
-the short arm of an acrocentric chromosome or intersects a
-centromere, returns an empty string.
    
-
    
-
    contigstr
    Chromosome of interval.
    
-
    
-
    startint
    Start of interval.
    
-
    
-
    stopint
    End of interval.
    
-
    
-
    
-
    
-
    Returns:
    
-
    arm – Arm that interval is in.
    
-
    
-
    Return type:
    
-
    str
    
-
    
-
    Raises:
    
-
    ValueError – Raised for invalid coordinates
    
-
    
-
    
-
    
-
-
    
-
    
-get_contig_gaps(contig: str) → ContigGaps#
    
-
    Creates a ContigGaps for the specified chromosome
    
-
    
-
    Parameters:
    
-
    contig (str) – Chromosome to make ContigGaps for
    
-
    
-
    Returns:
    
-
    Contains centromere and telomere intervals for chromosome
    
-
    
-
    Return type:
    
-
    ContigGaps
    
-
    
-
    
-
    
-
-
    
-
    
-classmethod hg38()#
    
-
    Creates a GenomeGaps for the hg38 reference genome. This
-sequences uses chromosome names that start with ‘chr’ and is
-synonymous with the GRCh38 reference genome.
-:returns: gaps – GenomeGaps for the hg38 reference genome.
-:rtype: GenomeGaps
    
-
    
-
-
    
-
    
-in_tcmere(contig: str, start: int, stop: int) → bool#
    
-
    Checks if specified interval is in a centromere or telomere
    
-
    
-
    Parameters:
    
-
      
-
    • contig (str) – Chromosome name
      • 
-
    • start (int) – Start of interval
      • 
-
    • stop (int) – End of interval
      • 
-
    
-
    
-
    Returns:
    
-
    in_telomere_or_centromere – True if in a centromere or telomere
    
-
    
-
    Return type:
    
-
    bool
    
-
    
-
    
-
    
-
-
    
-
    
-overlaps_gap(contig: str, start: int, stop: int) → bool#
    
-
    Checks if specified interval overlaps a gap interval
    
-
    
-
    Parameters:
    
-
      
-
    • contig (str) – Chromosome name
      • 
-
    • start (int) – Start of interval
      • 
-
    • stop (int) – End of interval
      • 
-
    
-
    
-
    Returns:
    
-
    in_telomere_or_centromere – True if in a centromere or telomere
    
-
    
-
    Return type:
    
-
    bool
    
-
    
-
    
-
    
-
-
    
-
    
-to_bed(output_file: str)#
    
-
    Prints gap intervals in GenomeGaps to a BED4 file where the name
-is the type of gap interval.
    
-
    
-
    Parameters:
    
-
    output_file (str) – File to write to. Optionally gzipped. If output_file == ‘-‘,
-results will be writted to stdout.
    
-
    
-
    
-
    
-
-
    
-
    
-classmethod ucsc_hg19()#
    
-
    Creates a GenomeGaps for the UCSC hg19 reference genome. This
-sequences uses chromosome names that start with ‘chr’ and is
-based on a version of the GRCh37 reference genome.
    
-
    
-
    Returns:
    
-
    gaps – GenomeGaps for the UCSC hg19 reference genome.
    
-
    
-
    Return type:
    
-
    GenomeGaps
    
-
    
-
    
-
    
-
-
    
-
-
    
-
    
-class finaletoolkit.genome.ContigGaps(contig: str, centromere: tuple[int, int], telomeres: Iterable[tuple[int, int]], has_short_arm: bool = False)#
    
-
    
-
    
-get_arm(start: int, stop: int)#
    
-
    Returns name of chromosome arm the interval is in. Returns
-“NOARM” if in a centromere, telomere, or short arm of an
-acrocentric chromosome.
    
-
    
-
    Parameters:
    
-
      
-
    • start (int) – Start of interval.
      • 
-
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      • 
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-in_gap(start: int, stop: int) → bool#
    
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-
      
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    • start (int) – Start of interval.
      • 
-
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      • 
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      • 
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-finaletoolkit.genome.ucsc_hg19_gap_bed(output_file: str)#
    
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-hg19 reference sequence.
    
-
    
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    output_file (str) – Output path
    
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-finaletoolkit.genome.b37_gap_bed(output_file: str)#
    
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    Creates BED4 of centromeres, telomeres, and short arms for the Broad
-Institute GRCh37 (b37) reference sequence. Also useful for
-files aligned to human_g1k_v37 (1000 Genomes Project).
    
-
    
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-
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-finaletoolkit.genome.ucsc_hg38_gap_bed(output_file: str)#
    
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    Creates BED4 of centromeres, telomeres, and short arms for the UCSC
-hg38 reference sequence.
    
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diff --git a/source/api_reference/wps.html b/source/api_reference/wps.html
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    Window Protection Score (WPS)#
    
-
    
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-finaletoolkit.frag.wps(input_file: str | AlignmentFile, contig: str, start: int | str, stop: int | str, output_file: str | None = None, window_size: int = 120, fraction_low: int = 120, fraction_high: int = 180, quality_threshold: int = 30, verbose: bool | int = 0) → ndarray#
    
-
    Return (raw) Windowed Protection Scores as specified in Snyder et al
-(2016) over a region [start,stop).
    
-
    
-
    Parameters:
    
-
      
-
    • input_file (str or pysam.AlignmentFile) – BAM, SAM or tabix file containing paired-end fragment reads or its
-path. AlignmentFile must be opened in read mode.
      • 
-
    • contig (str)
      • 
-
    • start (int)
      • 
-
    • stop (int)
      • 
-
    • output_file (string, optional)
      • 
-
    • window_size (int, optional) – Size of window to calculate WPS. Default is k = 120, equivalent
-to L-WPS.
      • 
-
    • fraction_low (int, optional) – Specifies lowest fragment length included in calculation.
-Default is 120, equivalent to long fraction.
      • 
-
    • fraction_high (int, optional) – Specifies highest fragment length included in calculation.
-Default is 180, equivalent to long fraction.
      • 
-
    • quality_threshold (int, optional)
      • 
-
    • workers (int, optional)
      • 
-
    • verbose (bool, optional)
      • 
-
    
-
    
-
    Returns:
    
-
    scores – np struct array of with columns contig, start, and wps.
    
-
    
-
    Return type:
    
-
    numpy.ndarray
    
-
    
-
    
-
    
-
-
    
-
    
-finaletoolkit.frag.multi_wps(input_file: AlignmentFile | str, site_bed: str, output_file: None | str = None, window_size: int = 120, interval_size: int = 5000, fraction_low: int = 120, fraction_high: int = 180, quality_threshold: int = 30, workers: int = 1, verbose: bool | int = 0) → ndarray#
    
-
    Function that aggregates WPS over sites in BED file according to the
-method described by Snyder et al (2016).
    
-
    
-
    Parameters:
    
-
      
-
    • input_file (str or pysam.AlignmentFile) – BAM, SAM, or tabix file containing paired-end fragment reads or its
-path. AlignmentFile must be opened in read mode.
      • 
-
    • site_bed (str) – Bed file containing intervals to perform WPS on.
      • 
-
    • output_file (string, optional)
      • 
-
    • window_size (int, optional) – Size of window to calculate WPS. Default is k = 120, equivalent
-to L-WPS.
      • 
-
    • interval_size (int, optional) – Size of each interval specified in the bed file. Should be the
-same for every interbal. Default is 5000.
      • 
-
    • fraction_low (int, optional) – Specifies lowest fragment length included in calculation.
-Default is 120, equivalent to long fraction.
      • 
-
    • fraction_high (int, optional) – Specifies highest fragment length included in calculation.
-Default is 120, equivalent to long fraction.
      • 
-
    • quality_threshold (int, optional)
      • 
-
    • workers (int, optional)
      • 
-
    • verbose (bool, optional)
      • 
-
    
-
    
-
    Returns:
    
-
    scores – np array of shape (n, 2) where column 1 is the coordinate and
-column 2 is the score and n is the number of coordinates in
-region [start,stop)
    
-
    
-
    Return type:
    
-
    numpy.ndarray
    
-
    
-
    
-
    
-
-
    
-
    
-finaletoolkit.frag.adjust_wps(input_file: str, interval_file: str, output_file: str, genome_file: str, median_window_size: int = 1000, savgol_window_size: int = 21, savgol_poly_deg: int = 2, mean: bool = False, subtract_edges: bool = False, edge_size: int = 500, workers: int = 1, verbose: Union(bool, int) = False)#
    
-
    Adjusts raw WPS data in a BigWig by applying a median filter and
-Savitsky-Golay filter (Savitsky and Golay, 1964).
    
-
    
-
    Parameters:
    
-
      
-
    • input_file (str) – Path string to a BigWig containing raw WPS data.
      • 
-
    • interval_file (str) – BED format file containing intervals over which WPS was
-calculated on.
      • 
-
    • output_file (str) – BigWig file to write adjusted WPS to.
      • 
-
    • genome_file (str) – The genome file for the reference genome that WGS was aligned
-to. A tab delimited file where column 1 contains the name of
-chromosomes and column 2 contains chromosome length.
      • 
-
    • median_window_size (int, optional) – Size of median filter window. Default is 1000.
      • 
-
    • savgol_window_size (int, optional) – Size of Savitsky Golay filter window. Default is 21.
      • 
-
    • savgol_poly_deg (int, optional) – Degree polynomial for Savitsky Golay filter. Default is 2.
      • 
-
    • mean (bool, optional) – If true, a mean filter is used instead of median. Default is
-False.
      • 
-
    • subtract_edges (bool, optional) – If true, take the median of the first and last 500 bases in a
-window and subtract from the whole interval. Default is False.
      • 
-
    • workers (int, optional) – Number of processes to use. Default is 1.
      • 
-
    • verbose (bool or int, optional) – Default is False.
      • 
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diff --git a/source/cli_reference/index.html b/source/cli_reference/index.html
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    CLI#
    
-
    FinaleToolkit is a package and standalone program to extract fragmentation features of cell-free DNA from paired-end sequencing data.
    
-
    
-
    usage: finaletoolkit [-h] [-v]
-                     {coverage,frag-length-bins,frag-length-intervals,cleavage-profile,wps,adjust-wps,delfi,delfi-gc-correct,end-motifs,interval-end-motifs,mds,interval-mds,filter-bam,agg-bw,gap-bed}
-                     ...
-
    
-
    
-
    
-
    Named Arguments#
    
-
    
-
    -v, --version
    
-
    show program’s version number and exit
    
-
    
-
    
-
    
-
    
-
    Sub-commands#
    
-
    
-
    coverage#
    
-
    Calculates fragmentation coverage over intervals defined in a BED file based on alignment data from a BAM/SAM/CRAM/Fragment file.
    
-
    finaletoolkit coverage [-h] [-o OUTPUT_FILE] [-s SCALE_FACTOR] [-q QUALITY_THRESHOLD] [-w WORKERS] [-v] input_file interval_file
-
    
-
    
-
    
-
    Positional Arguments#
    
-
    
-
    input_file
    
-
    Path to a BAM/SAM/CRAM/Fragment file containing fragment data.
    
-
    
-
    interval_file
    
-
    Path to a BED file containing intervals to calculate coverage over.
    
-
    
-
    
-
    
-
    
-
    Named Arguments#
    
-
    
-
    -o, --output_file
    
-
    A BED file containing coverage values over the intervals specified in interval file.
    
-
    Default: “-”
    
-
    
-
    -s, --scale-factor
    
-
    Scale factor for coverage values.
    
-
    Default: 1000000.0
    
-
    
-
    -q, --quality_threshold
    
-
    Minimum mapping quality threshold.
    
-
    Default: 30
    
-
    
-
    -w, --workers
    
-
    Number of worker processes.
    
-
    Default: 1
    
-
    
-
    -v, --verbose
    
-
    Enable verbose mode to display detailed processing information.
    
-
    Default: False
    
-
    
-
    
-
    
-
    
-
    
-
    frag-length-bins#
    
-
    Retrieves fragment lengths grouped in bins given a BAM/SAM/CRAM/Fragment file.
    
-
    finaletoolkit frag-length-bins [-h] [-c CONTIG] [-S START] [-p {midpoint,any}] [-E STOP] [--bin-size BIN_SIZE] [-o OUTPUT_FILE] [--contig-by-contig] [--histogram] [-q QUALITY_THRESHOLD] [-v]
-                               input_file
-
    
-
    
-
    
-
    Positional Arguments#
    
-
    
-
    input_file
    
-
    Path to a BAM/SAM/CRAM/Fragment file containing fragment data.
    
-
    
-
    
-
    
-
    
-
    Named Arguments#
    
-
    
-
    -c, --contig
    
-
    Specify the contig or chromosome to select fragments from. (Required if using –start or –stop.)
    
-
    
-
    -S, --start
    
-
    Specify the 0-based left-most coordinate of the interval to select fragments from. (Must also specify –contig.)
    
-
    
-
    -p, --intersect_policy
    
-
    Possible choices: midpoint, any
    
-
    Specifies what policy is used to include fragments in the given interval. See User Guide for more information.
    
-
    Default: “midpoint”
    
-
    
-
    -E, --stop
    
-
    Specify the 1-based right-most coordinate of the interval to select fragments from. (Must also specify –contig.)
    
-
    
-
    --bin-size
    
-
    Specify the size of the bins to group fragment lengths into.
    
-
    
-
    -o, --output_file
    
-
    A .TSV file containing containing fragment lengths binned according to the specified bin size.
    
-
    Default: “-”
    
-
    
-
    --contig-by-contig
    
-
    Placeholder, not implemented.
    
-
    Default: False
    
-
    
-
    --histogram
    
-
    Enable histogram mode to display histogram in terminal.
    
-
    Default: False
    
-
    
-
    -q, --quality_threshold
    
-
    Minimum mapping quality threshold.
    
-
    Default: 30
    
-
    
-
    -v, --verbose
    
-
    Enable verbose mode to display detailed processing information.
    
-
    Default: 0
    
-
    
-
    
-
    
-
    
-
    
-
    frag-length-intervals#
    
-
    Retrieves fragment length summary statistics over intervals defined in a BED file based on alignment data from a BAM/SAM/CRAM/Fragment file.
    
-
    finaletoolkit frag-length-intervals [-h] [-p {midpoint,any}] [-o OUTPUT_FILE] [-q QUALITY_THRESHOLD] [-w WORKERS] [-v] input_file interval_file
-
    
-
    
-
    
-
    Positional Arguments#
    
-
    
-
    input_file
    
-
    Path to a BAM/SAM/CRAM/Fragment file containing fragment data.
    
-
    
-
    interval_file
    
-
    Path to a BED file containing intervals to retrieve fragment length summary statistics over.
    
-
    
-
    
-
    
-
    
-
    Named Arguments#
    
-
    
-
    -p, --intersect_policy
    
-
    Possible choices: midpoint, any
    
-
    Specifies what policy is used to include fragments in the given interval. See User Guide for more information.
    
-
    Default: “midpoint”
    
-
    
-
    -o, --output-file
    
-
    A BED file containing fragment length summary statistics (mean, median, st. dev, min, max) over the intervals specified in the interval file.
    
-
    Default: “-”
    
-
    
-
    -q, --quality-threshold
    
-
    Minimum mapping quality threshold.
    
-
    Default: 30
    
-
    
-
    -w, --workers
    
-
    Number of worker processes.
    
-
    Default: 1
    
-
    
-
    -v, --verbose
    
-
    Enable verbose mode to display detailed processing information.
    
-
    Default: 0
    
-
    
-
    
-
    
-
    
-
    
-
    cleavage-profile#
    
-
    Calculates cleavage proportion over intervals defined in a BED file based on alignment data from a BAM/SAM/CRAM/Fragment file.
    
-
    finaletoolkit cleavage-profile [-h] [-o OUTPUT_FILE] [-lo FRACTION_LOW] [-hi FRACTION_HIGH] [-q QUALITY_THRESHOLD] [-l LEFT] [-r RIGHT] [-w WORKERS] [-v] input_file interval_file
-
    
-
    
-
    
-
    Positional Arguments#
    
-
    
-
    input_file
    
-
    Path to a BAM/SAM/CRAM/Fragment file containing fragment data.
    
-
    
-
    interval_file
    
-
    Path to a BED file containing intervals to calculates cleavage proportion over.
    
-
    
-
    
-
    
-
    
-
    Named Arguments#
    
-
    
-
    -o, --output_file
    
-
    A bigWig file containing the cleavage proportion results over the intervals specified in interval file.
    
-
    Default: “-”
    
-
    
-
    -lo, --fraction_low
    
-
    Minimum length for a fragment to be included in cleavage proportion calculation.
    
-
    Default: 120
    
-
    
-
    -hi, --fraction_high
    
-
    Maximum length for a fragment to be included in cleavage proportion calculation.
    
-
    Default: 180
    
-
    
-
    -q, --quality-threshold
    
-
    Minimum mapping quality threshold.
    
-
    Default: 20
    
-
    
-
    -l, --left
    
-
    Number of base pairs to subtract from start coordinate to create interval. Useful when dealing with BED files with only CpG coordinates.
    
-
    Default: 0
    
-
    
-
    -r, --right
    
-
    Number of base pairs to add to stop coordinate to create interval. Useful when dealing with BED files with only CpG coordinates.
    
-
    Default: 0
    
-
    
-
    -w, --workers
    
-
    Number of worker processes.
    
-
    Default: 1
    
-
    
-
    -v, --verbose
    
-
    Enable verbose mode to display detailed processing information.
    
-
    Default: 0
    
-
    
-
    
-
    
-
    
-
    
-
    wps#
    
-
    Calculates Windowed Protection Score (WPS) over intervals defined in a BED file based on alignment data from a BAM/SAM/CRAM/Fragment file.
    
-
    finaletoolkit wps [-h] [-o OUTPUT_FILE] [-i INTERVAL_SIZE] [-W WINDOW_SIZE] [-lo FRACTION_LOW] [-hi FRACTION_HIGH] [-q QUALITY_THRESHOLD] [-w WORKERS] [-v] input_file site_bed
-
    
-
    
-
    
-
    Positional Arguments#
    
-
    
-
    input_file
    
-
    Path to a BAM/SAM/CRAM/Fragment file containing fragment data.
    
-
    
-
    site_bed
    
-
    Path to a BED file containing intervals to calculate WPS over.
    
-
    
-
    
-
    
-
    
-
    Named Arguments#
    
-
    
-
    -o, --output_file
    
-
    A bigWig file containing the WPS results over the intervals specified in interval file.
    
-
    Default: “-”
    
-
    
-
    -i, --interval_size
    
-
    Size in bp of each interval in the interval file.
    
-
    Default: 5000
    
-
    
-
    -W, --window_size
    
-
    Size of the sliding window used to calculate WPS scores.
    
-
    Default: 120
    
-
    
-
    -lo, --fraction_low
    
-
    Minimum length for a fragment to be included in WPS calculation.
    
-
    Default: 120
    
-
    
-
    -hi, --fraction_high
    
-
    Maximum length for a fragment to be included in WPS calculation.
    
-
    Default: 180
    
-
    
-
    -q, --quality_threshold
    
-
    Minimum mapping quality threshold.
    
-
    Default: 30
    
-
    
-
    -w, --workers
    
-
    Number of worker processes.
    
-
    Default: 1
    
-
    
-
    -v, --verbose
    
-
    Enable verbose mode to display detailed processing information.
    
-
    Default: 0
    
-
    
-
    
-
    
-
    
-
    
-
    adjust-wps#
    
-
    Adjusts raw Windowed Protection Score (WPS) by applying a median filter and Savitsky-Golay filter.
    
-
    finaletoolkit adjust-wps [-h] [-o OUTPUT_FILE] [-m MEDIAN_WINDOW_SIZE] [-s SAVGOL_WINDOW_SIZE] [-p SAVGOL_POLY_DEG] [-w WORKERS] [--mean] [--subtract-edges] [-v] input_file interval_file genome_file
-
    
-
    
-
    
-
    Positional Arguments#
    
-
    
-
    input_file
    
-
    A bigWig file containing the WPS results over the intervals specified in interval file.
    
-
    
-
    interval_file
    
-
    Path to a BED file containing intervals to WPS was calculated over.
    
-
    
-
    genome_file
    
-
    A .chrom.sizes file containing chromosome sizes.
    
-
    
-
    
-
    
-
    
-
    Named Arguments#
    
-
    
-
    -o, --output-file
    
-
    A bigWig file containing the adjusted WPS results over the intervals specified in interval file.
    
-
    Default: “-”
    
-
    
-
    -m, --median-window-size
    
-
    Size of the median filter window used to adjust WPS scores.
    
-
    Default: 1000
    
-
    
-
    -s, --savgol-window-size
    
-
    Size of the Savitsky-Golay filter window used to adjust WPS scores.
    
-
    Default: 21
    
-
    
-
    -p, --savgol-poly-deg
    
-
    Degree polynomial for Savitsky-Golay filter.
    
-
    Default: 2
    
-
    
-
    -w, --workers
    
-
    Number of worker processes.
    
-
    Default: 1
    
-
    
-
    --mean
    
-
    A mean filter is used instead of median.
    
-
    Default: False
    
-
    
-
    --subtract-edges
    
-
    Take the median of the first and last 500 bases in a window and subtract from the whole interval.
    
-
    Default: False
    
-
    
-
    -v, --verbose
    
-
    Enable verbose mode to display detailed processing information.
    
-
    
-
    
-
    
-
    
-
    
-
    delfi#
    
-
    Calculates DELFI featrues over genome, returning information about (GC-corrected) short fragments, long fragments, DELFI ratio, and total fragments. NOTE: Due to some ad hoc implementation details, currently the only accepted reference genome is hg19.
    
-
    finaletoolkit delfi [-h] [-b BLACKLIST_FILE] [-g GAP_FILE] [-o OUTPUT_FILE] [-W WINDOW_SIZE] [-gc] [-m] [-q QUALITY_THRESHOLD] [-w WORKERS] [-v] input_file autosomes reference_file bins_file
-
    
-
    
-
    
-
    Positional Arguments#
    
-
    
-
    input_file
    
-
    Path to a BAM/SAM/CRAM/Fragment file containing fragment data.
    
-
    
-
    autosomes
    
-
    Tab-delimited file containing (1) autosome name and (2) integer length of chromosome in base pairs.
    
-
    
-
    reference_file
    
-
    The .2bit file for the associate reference genome sequence used during alignment.
    
-
    
-
    bins_file
    
-
    A BED file containing bins over which to calculate DELFI. To replicate Cristiano et al.’s methodology, use 100kb bins over human autosomes.
    
-
    
-
    
-
    
-
    
-
    Named Arguments#
    
-
    
-
    -b, --blacklist_file
    
-
    BED file containing regions to ignore when calculating DELFI.
    
-
    
-
    -g, --gap_file
    
-
    BED4 format file containing columns for “chrom”, “start”, “stop”, and “type”. The “type” column should denote whether the entry corresponds to a “centromere”, “telomere”, or “short arm”, and entries not falling into these categories are ignored. This information corresponds to the “gap” track for hg19 in the UCSC Genome Browser.
    
-
    
-
    -o, --output_file
    
-
    BED, bed.gz, TSV, or CSV file to write DELFI data to. If “-”, writes to stdout.
    
-
    Default: “-”
    
-
    
-
    -W, --window_size
    
-
    Currently unused.
    
-
    Default: 5000000
    
-
    
-
    -gc, --gc_correct
    
-
    Indicates whether to apply GC correction.
    
-
    Default: False
    
-
    
-
    -m, --merge_bins
    
-
    Indicates whether to merge bins to 5Mb size.
    
-
    Default: False
    
-
    
-
    -q, --quality_threshold
    
-
    Minimum mapping quality threshold.
    
-
    Default: 30
    
-
    
-
    -w, --workers
    
-
    Number of worker processes.
    
-
    Default: 1
    
-
    
-
    -v, --verbose
    
-
    Enable verbose mode to display detailed processing information.
    
-
    Default: 0
    
-
    
-
    
-
    
-
    
-
    
-
    delfi-gc-correct#
    
-
    Performs gc-correction on raw delfi data.
    
-
    finaletoolkit delfi-gc-correct [-h] [-o OUTPUT_FILE] [--header-lines HEADER_LINES] [-v] input_file
-
    
-
    
-
    
-
    Positional Arguments#
    
-
    
-
    input_file
    
-
    BED file containing raw DELFI data. Raw DELFI data should only have columns for “contig”, “start”, “stop”, “arm”, “short”, “long”, “gc”, “num_frags”, “ratio”.
    
-
    
-
    
-
    
-
    
-
    Named Arguments#
    
-
    
-
    -o, --output-file
    
-
    BED to print GC-corrected DELFI fractions. If “-”, will write to stdout.
    
-
    Default: “-”
    
-
    
-
    --header-lines
    
-
    Number of header lines in BED.
    
-
    Default: 1
    
-
    
-
    -v, --verbose
    
-
    Enable verbose mode to display detailed processing information.
    
-
    
-
    
-
    
-
    
-
    
-
    end-motifs#
    
-
    Measures frequency of k-mer 5’ end motifs.
    
-
    finaletoolkit end-motifs [-h] [-k K] [-o OUTPUT_FILE] [-q QUALITY_THRESHOLD] [-w WORKERS] [-v] input_file refseq_file
-
    
-
    
-
    
-
    Positional Arguments#
    
-
    
-
    input_file
    
-
    Path to a BAM/SAM/CRAM/Fragment file containing fragment data.
    
-
    
-
    refseq_file
    
-
    The .2bit file for the associate reference genome sequence used during alignment.
    
-
    
-
    
-
    
-
    
-
    Named Arguments#
    
-
    
-
    -k
    
-
    Length of k-mer.
    
-
    Default: 4
    
-
    
-
    -o, --output-file
    
-
    TSV to print k-mer frequencies. If “-”, will write to stdout.
    
-
    Default: “-”
    
-
    
-
    -q, --quality-threshold
    
-
    Minimum mapping quality threshold.
    
-
    Default: 20
    
-
    
-
    -w, --workers
    
-
    Number of worker processes.
    
-
    Default: 1
    
-
    
-
    -v, --verbose
    
-
    Enable verbose mode to display detailed processing information.
    
-
    Default: 0
    
-
    
-
    
-
    
-
    
-
    
-
    interval-end-motifs#
    
-
    Measures frequency of k-mer 5’ end motifs in each region specified in a BED file and writes data into a table.
    
-
    finaletoolkit interval-end-motifs [-h] [-k K] [-lo FRACTION_LOW] [-hi FRACTION_HIGH] [-o OUTPUT_FILE] [-q QUALITY_THRESHOLD] [-w WORKERS] [-v] input_file refseq_file intervals
-
    
-
    
-
    
-
    Positional Arguments#
    
-
    
-
    input_file
    
-
    Path to a BAM/SAM/CRAM/Fragment file containing fragment data.
    
-
    
-
    refseq_file
    
-
    The .2bit file for the associate reference genome sequence used during alignment.
    
-
    
-
    intervals
    
-
    Path to a BED file containing intervals to retrieve end motif frequencies over.
    
-
    
-
    
-
    
-
    
-
    Named Arguments#
    
-
    
-
    -k
    
-
    Length of k-mer.
    
-
    Default: 4
    
-
    
-
    -lo, --fraction-low
    
-
    Minimum length for a fragment to be included in end motif frequency.
    
-
    Default: 10
    
-
    
-
    -hi, --fraction-high
    
-
    Maximum length for a fragment to be included in end motif frequency.
    
-
    Default: 600
    
-
    
-
    -o, --output-file
    
-
    Path to TSV or CSV file to write end motif frequencies to.
    
-
    Default: “-”
    
-
    
-
    -q, --quality-threshold
    
-
    Minimum mapping quality threshold.
    
-
    Default: 20
    
-
    
-
    -w, --workers
    
-
    Number of worker processes.
    
-
    Default: 1
    
-
    
-
    -v, --verbose
    
-
    Enable verbose mode to display detailed processing information.
    
-
    Default: 0
    
-
    
-
    
-
    
-
    
-
    
-
    mds#
    
-
    Reads k-mer frequencies from a file and calculates a motif diversity score (MDS) using normalized Shannon entropy as described by Jiang et al (2020).
    
-
    finaletoolkit mds [-h] [-s SEP] [--header HEADER] [file_path]
-
    
-
    
-
    
-
    Positional Arguments#
    
-
    
-
    file_path
    
-
    Tab-delimited or similar file containing one column for all k-mers a one column for frequency. Reads from stdin by default.
    
-
    Default: “-”
    
-
    
-
    
-
    
-
    
-
    Named Arguments#
    
-
    
-
    -s, --sep
    
-
    Separator used in tabular file.
    
-
    Default: “      “
    
-
    
-
    --header
    
-
    Number of header rows to ignore. Default is 0
    
-
    Default: 0
    
-
    
-
    
-
    
-
    
-
    
-
    interval-mds#
    
-
    Reads k-mer frequencies from a file and calculates a motif diversity score (MDS) for each interval using normalized Shannon entropy as described by Jiang et al (2020).
    
-
    finaletoolkit interval-mds [-h] [-s SEP] [file_path] file_out
-
    
-
    
-
    
-
    Positional Arguments#
    
-
    
-
    file_path
    
-
    Tab-delimited or similar file containing one column for all k-mers a one column for frequency. Reads from stdin by default.
    
-
    Default: “-”
    
-
    
-
    file_out
    
-
    Path to the output BED/BEDGraph file containing MDS for each interval.
    
-
    Default: “-”
    
-
    
-
    
-
    
-
    
-
    Named Arguments#
    
-
    
-
    -s, --sep
    
-
    Separator used in tabular file.
    
-
    Default: “      “
    
-
    
-
    
-
    
-
    
-
    
-
    filter-bam#
    
-
    Filters a BAM file so that all reads are in mapped pairs, exceed a certain MAPQ, are not flagged for quality, are read1, are not secondary or supplementary alignments, and are on the same reference sequence as the mate.
    
-
    finaletoolkit filter-bam [-h] [-r REGION_FILE] [-o OUTPUT_FILE] [-q QUALITY_THRESHOLD] [-hi FRACTION_HIGH] [-lo FRACTION_LOW] [-w WORKERS] [-v] input_file
-
    
-
    
-
    
-
    Positional Arguments#
    
-
    
-
    input_file
    
-
    Path to BAM file.
    
-
    
-
    
-
    
-
    
-
    Named Arguments#
    
-
    
-
    -r, --region-file
    
-
    Only output alignments overlapping the intervals in this BED file will be included.
    
-
    
-
    -o, --output-file
    
-
    Output BAM file path.
    
-
    Default: “-”
    
-
    
-
    -q, --quality_threshold
    
-
    Minimum mapping quality threshold.
    
-
    Default: 30
    
-
    
-
    -hi, --fraction-high
    
-
    Maximum length for a fragment to be included in output BAM.
    
-
    
-
    -lo, --fraction-low
    
-
    Minimum length for a fragment to be included in output BAM.
    
-
    
-
    -w, --workers
    
-
    Number of worker processes.
    
-
    Default: 1
    
-
    
-
    -v, --verbose
    
-
    Enable verbose mode to display detailed processing information.
    
-
    
-
    
-
    
-
    
-
    
-
    agg-bw#
    
-
    Aggregates a bigWig signal over constant-length intervals defined in a BED file.
    
-
    finaletoolkit agg-bw [-h] [-o OUTPUT_FILE] [-m MEDIAN_WINDOW_SIZE] [-v] input_file interval_file
-
    
-
    
-
    
-
    Positional Arguments#
    
-
    
-
    input_file
    
-
    
-
    A bigWig file containing signals over the intervals specified in interval file.
    
-
    
-
    
-
    interval_file
    
-
    Path to a BED file containing intervals over which signals were calculated over.
    
-
    
-
    
-
    
-
    
-
    Named Arguments#
    
-
    
-
    -o, --output-file
    
-
    A wiggle file containing the aggregate signal over the intervals specified in interval file.
    
-
    Default: “-”
    
-
    
-
    -m, --median-window-size
    
-
    Size of the median filter window used to adjust WPS scores. Only modify if aggregating WPS signals.
    
-
    Default: 0
    
-
    
-
    -v, --verbose
    
-
    Enable verbose mode to display detailed processing information.
    
-
    
-
    
-
    
-
    
-
    
-
    gap-bed#
    
-
    Creates a BED4 file containing centromeres, telomeres, and short-arm intervals, similar to the gaps annotation track for hg19 found on the UCSC Genome Browser (Kent et al 2002). Currently only supports hg19, b37, human_g1k_v37, hg38, and GRCh38
    
-
    finaletoolkit gap-bed [-h] {hg19,b37,human_g1k_v37,hg38,GRCh38} output_file
-
    
-
    
-
    
-
    Positional Arguments#
    
-
    
-
    reference_genome
    
-
    Possible choices: hg19, b37, human_g1k_v37, hg38, GRCh38
    
-
    Reference genome to provide gaps for.
    
-
    
-
    output_file
    
-
    Path to write BED file to. If “-” used, writes to stdout.
    
-
    
-
    
-
    
-
    Gap is used liberally in this command, and in the case hg38/GRCh38, may refer to regions where there no longer are gaps in the reference sequence.
    
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    A fragment file (.frag.gz) file that is derived from information in a BAM file. A fragment file is a block-gzipped BED3+2 file (similar to a tab-separated value file) that contains the following columns (with one row entry for each fragment): chrom, start, stop, mapq, and strand.
    
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    #chrom    start    stop    mapq    strand
-chr1    10000    10050    60    +
-chr1    10050    10100    60    -
-chr1    10100    10150    60    +
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    Introduction#
    
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    Circulating cell-free DNA (cfDNA) refers to highly fragmented DNA that circulate in blood plasma. In healthy conditions, cfDNA mainly originates from hematopoietic cells through apoptosis or necrosis. In pathological states, additional cfDNA is released from the genomes of otherwise inaccessible tissues (e.g., from tumors in cancer).
    
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    CfDNA fragmentation patterns have been established as a promising non-invasive biomarker for disease detection and monitoring. It has been shown that fragmentation pattern and cfDNA tissue-of-origin changes are associated with changes in different pathological statuses.
    
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    Computational approaches can extract fragmentation features from cfDNA whole genome sequencing (WGS) data. However, various established cfDNA fragmentation features (ex. Windowed Protection Score (WPS), Motif Diversity Score (MDS), DELFI) have source code which is often absent, poorly documented, ad hoc, and unmaintained.
    
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    FinaleToolkit offers a solution to this. It is a fast and comprehensive toolkit that provides a user-friendly interface to extract various cfDNA fragmentation features from fragmentation data. It is designed to be easy to use, well-documented, and maintained.
    
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