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pathfindR (development version)

pathfindR 1.6.2

Major Changes

  • fixed an issue in get_kegg_gsets() where empty result was returned for some organisms due to an error in parsing (#72)

Minor changes and bug fixes

  • added repel = TRUE in term_gene_graph() and combined_results_graph() for better visualization of labels
  • fixed minor issue in enrichment_chart() (#75)
  • fixed minor issue in visualize_term_interactions()
  • fixed issue in get_biogrid_pin() where the download method was set to wget (now set to auto, per #83)
  • updated to using tab3 format for get_biogrid_pin() (if tab3 is available for the chosen release, otherwise tab2 format is used)
  • updated the default version of PIN obtained by get_biogrid_pin() to '4.4.200'
  • in get_kegg_gsets(), improved parsing of KEGG term descriptions so that no description is duplicated (#87)
  • in score_terms(), if using descriptions, the ID is now appended for (any) duplicated term descriptions (#87)
  • in obtain_colored_url(), swapped bg_color with fg_color due to an issue with KEGGREST
  • added legend to term_gene_heatmap() (#95)
  • in get_biogrid_pin(), the "download.file.method" from global options is used
  • combined_results_graph() raises an error if there are no common terms in the combined data frame

pathfindR 1.6.1

Major Changes

  • In run_pathfindR(), the default iterations was set back to 10 (the default for all other v1.x)

pathfindR 1.6.0

Major Changes

  • In run_pathfindR(), as "GR" (the default active subnetwork search method) provides nearly identical results in each iteration, the default iterations is set to 1
  • added the column 'support' (the proportion of active subnetworks leading to enrichment over all subnetworks) in the output
  • updated the download URL in get_biogrid_pin() as BioGRID updated the URL for download

Minor changes and bug fixes

  • changed old argument in the "Step-by-Step Execution of the pathfindR Enrichment Workflow" vignette
  • fixed an issue in visualize_term_interactions() where the file name was too long, it was causing an error on Windows. Limited to 100 characters (#58)

pathfindR 1.5.1

Minor changes and bug fixes

  • Fixed issue in check_java_version() where java version 14 could not be parsed (#49)
  • Fixed issue in combined_results_graph() where gene nodes were not colored correctly (#55)

pathfindR 1.5.0

Major Changes

  • created separate package pathfindR.data for storing pathfindR data
  • added the function visualize_active_subnetworks() for visualizing graphs of active subnetworks
  • add the new vignette "Comparing Two pathfindR Results" that briefly describes how different pathfindR results can be compared
  • added the functions combine_pathfindR_results() and combined_results_graph() for comparison of 2 pathfindR results and term-gene graph of the combined results, respectively
  • added the function get_pin_file() for obtaining organism-specific PIN data (only from BioGRID for now)
  • added the function get_gene_sets_list() for obtaining organism-specific gene sets list from KEGG, Reactome and MSigDB
  • added the function term_gene_heatmap() to create heatmap visualizations of enriched terms and the involved input genes. Rows are enriched terms and columns are involved input genes. If genes_df is provided, colors of the tiles indicate the change values
  • added the function UpSet_plot() to create UpSet plots of enriched terms
  • added the human cell markers gene sets data cell_markers_gsets and cell_markers_descriptions

Minor changes and bug fixes

  • fixed an issue regarding parallel::makeCluster() in run_pathfindR() (#45)
  • fixed save-related issue in download_kegg_png() (#37, @rix133)
  • added the output data RA_comparison_output of pathfindR results on another RA-related dataset (GSE84074)
  • in visualize_hsa_KEGG(), fixed the issue where >1 entrez ids were returned for a gene symbol (the first one is kept)
  • in visualize_hsa_KEGG(), implemented a tryCatch to avoid any issues when KEGGREST::color.pathway.by.objects() might fail (#28)
  • in visualize_hsa_KEGG(), now limiting the number of genes passes onto KEGGREST::color.pathway.by.objects() to < 60 (because the KEGG API now limits the number?)
  • changed default visualization in term_gene_heatmap() (i.e. when genes_df is not provided) to binary colored heatmap (by default, "green" and "red", controlled by low and high) by up-/down- regulation status
  • update the vignette "pathfindR Analysis for non-Homo-sapiens organisms" to reflect new data generation functions get_pin_file() and get_gene_sets_list() and fixed a minor issue in the vignette (#46)

pathfindR 1.4.2

Minor changes and bug fixes

  • Fixed corner case in create_kappa_matrix() when chance is 1, the metric is turned into 0
  • Fixed misused class(.) == * in cluster_graph_vis()

pathfindR 1.4.1

Major Changes

  • Fixed error in DESCRIPTION: the Java version in SystemRequirements was corrected to "Java (>= 8.0)"
  • The Java version is now checked

Minor changes and bug fixes

  • Fixed behavior: when no input genes are present in the enriched hsa KEGG pathway, visualization of the pathway is now skipped
  • Added the argument max_to_plot to visualize_hsa_KEGG() and to run_pathfindR(). This argument controls the number of pathways to be visualized (default is NULL, i.e. no filter). This was implemented not to slow down the runtime of run_pathfindR() as downloading the png files is slow.
  • Fixed links to visualizations in enriched_ters.Rmd

pathfindR 1.4.0

Major Changes

  • Replaced most occurrences of "pathway" to "term". This was adapted because "term" reflects the utility of the package better. The enrichment and clustering approaches work with any kind of gene set data (be it pathway gene sets, gene ontology gene sets, motif gene sets etc.) Accordingly:
    • DESCRIPTION was updated
    • The functions annotate_pathway_DEGs(), calculate_pw_scores(), cluster_pathways(), fuzzy_pw_clustering(), hierarchical_pw_clustering(), visualize_pw_interactions() and visualize_pws() were renamed to annotate_term_DEGs(), score_terms(), cluster_enriched_terms(), fuzzy_term_clustering(), hierarchical_term_clustering(), visualize_term_interactions() and visualize_terms() respectively
    • The Rmd template file for the report enriched_pathways.Rmd was renamed to enriched_terms.Rmd
    • All the Rmd template files for the report were updated
    • Documentation of each function was updated accordingly
  • Added the visualization function term_gene_graph(), which creates a graph of enriched terms - involved genes
  • Made changes in enrichment() and enrichment_analyses() to get enrichment results faster
  • Added the function fetch_gene_set() for obtaining gene set data more easily
  • Terms in gene sets can now be filtered according to the number of genes a term contains (controlled by min_gset_size, max_gset_size in fetch_gene_set() and run_pathfindR())
  • Added the argument gaCrossover during active subnetwork search which controls the probability of a crossover in GA (default = 1, i.e. always perform crossover)
  • Added unit tests using testthat
  • Updated all gene sets data
  • Updated all RA example data
  • The vignettes were updated
  • Updated all PIN data
  • Improved speed of kappa matrix calculation (create_kappa_matrix())
  • Added vignette for non-Homo-sapiens organisms
  • Added Mus musculus (mmu) data:
    • mmu_kegg_genes & mmu_kegg_descriptions: mmu KEGG gene sets data
    • mmu STRING PIN
    • myeloma_input & myeloma_output: example mmu input and output data
  • Added the STRING PIN (combined score >= 400)
  • The argument sig_gene_thr in subnetwork filtering via filterActiveSnws() now serves the threshold proportion of significant genes in the active subnetwork. e.g., if there are 100 significant genes and sig_gene_thr = 0.03, subnetwork that contain at least 3 (100 x 0.03) significant genes will be accepted for further analysis
  • Removed pathview dependency by implementing colored pathway diagram visualization function using KEGGREST and KEGGgraph

Minor changes and bug fixes

  • In hierarchical_term_clustering(), redefined the distance measure as 1 - kappa statistic
  • Fixed minor issue in cluster_graph_vis() (during the calculations for additional node colors)
  • Removed title from graph visualization of hierarchical clustering in cluster_graph_vis()
  • In active_snw_search(), unnecessary warnings during active subnetwork search were removed
  • Fixed minor issue in enrichment_chart(), supplying fuzzy clustered results no longer raises an error
  • Added new checks in input_testing() and input_processing() to ensure that both the initial input data frame and the processed input data frame for active subnetwork search contain at least 2 genes (to fix the corner case encountered in issue #17)
  • Fixed minor issue in enrichment_chart(), ensuring that bubble sizes displayed in the legend (proportional to # of DEGs) are integers
  • In enrichment_chart(), added the arguments num_bubbles (default is 4) to control number of bubbles displayed in the legend and even_breaks (default is TRUE) to indicate if even increments of breaks are required
  • Updated the logo
  • Minor fix in term_gene_graph() (create the igraph object as an undirected graph for better auto layout)
  • Minor fix in visualize_term_interactions(). The legend no longer displays "Non-input Active Snw. Genes" if they were not provided
  • The argument human_genes in run_pathfindR() and input_processing() was renamed as convert2alias
  • The gene symbols in the input data frame, the PIN and the gene sets are now turned into uppercase (for obtaining the best overlap)
  • Added the argument top_terms to enrichment_chart(), controlling the number top enriched terms to plot (default is 10)
  • Other minor bug/error fixes

pathfindR 1.3.0

Major Changes

  • Separated the steps of the function run_pathfindR into individual functions: active_snw_search, enrichment_analyses, summarize_enrichment_results, annotate_pathway_DEGs, visualize_pws.
  • renamed the function pathmap as visualize_hsa_KEGG, updated the function to produce different visualizations for inputs with binary change values (ordered) and no change values (the input_processing function, assigns a change value of 100 to all).
  • Created new the visualization function visualize_pw_interactions, which creates PNG files visualizing the interactions (in the selected PIN) of genes involved in the given pathways.
  • Added new vignette, describing the step-by-step execution of the pathfindR workflow
  • Changed clustering metric to kappa statistic, created the new clustering related functions create_kappa_matrix, hierarchical_pw_clustering, fuzzy_pw_clustering and cluster_pathways.
  • Implemented the new function cluster_graph_vis for visualizing graph diagrams of clustering results.

Minor changes and bug fixes

  • Fixed the bug where the arguments score_quan_thr and sig_gene_thr for run_pathfindR were not being utilized.
  • in run_pathfindR, added message at the end of run, reporting the number enriched pathways.
  • the function run_pathfindR now creates a variable org_dir that is the "path/to/original/working/directory". org_dir is used in multiple functions to return to the original working directory if anything fails. This changes the previous behavior where if a function stopped with an error the directory was changed to "..", i.e. the parent directory. This change was adapted so that the user is returned to the original working directory if they supply a recursive output folder (output_dir, e.g. "./ALL_RESULTS/RESULT_A").
  • in input_processing, added the argument human_genes to only perform alias symbol conversion when human gene symbols are provided. - Updated the Rmd files used to create the report HTML files
  • Added the data for GO-All, all annotations in the GO database (BP+MF+CC)
  • Updated the vignette pathfindR - An R Package for Pathway Enrichment Analysis Utilizing Active Subnetworks to reflect the new functionalities.

pathfindR 1.2.3

Minor changes and bug fixes

  • in the function plot_scores, added the argument label_cases to indicate whether or not to label the cases in the pathway scoring heatmap plot. Also added the argument case_control_titles which allows the user to change the default "Case" and "Control" headers. Also added the arguments low and high used to change the low and high end colors of the scoring color gradient.
  • in the function plot_scores, reversed the color gradient to match the coloring scheme used by pathview (i.e. red for positive values, green for negative values)
  • minor change in parseActiveSnwSearch, replaced score_thr by score_quan_thr. This was done so that the scoring filter for active subnetworks could be performed based on the distribution of the current active subnetworks and not using a constant empirical score value threshold.
  • minor change in parseActiveSnwSearch, increased sig_gene_thr from 2 to 10 as we observed in most of the cases, this resulted in faster runs with comparable results.
  • in choose_clusters, added the argument p_val_threshold to be used as p value threshold for filtering the enriched pathways prior to clustering.

pathfindR 1.2.2

Major Changes

  • fixed issue related to the package pathview.

Minor changes and bug fixes

  • in the function choose_clusters, added option to use pathway names instead of pathway ids when visualizing the clustering dendrogram and heatmap.

pathfindR 1.2.1

Major Changes

  • Added the option to specify a custom gene set when using run_pathfindR. For this, the gene_sets argument should be set to "Custom" and custom_genes and custom_pathways should be provided.

Minor changes and bug fixes

  • fixed minor bug in calculate_pw_scores where if there was one DEG, subsetting the experiment matrix failed
  • added if condition to check if there were DEGs in calculate_pw_scores. If there is none, the pathway is skipped.
  • in calculate_pw_scores, if cases are provided, the pathways are reordered before plotting the heat map and returning the matrix according to their activity in cases. This way, "up" pathways are grouped together, same for "down" pathways.
  • in calculate_pwd, if a pathway has perfect overlap with other pathways, change the correlation value with 1 instead of NA.
  • in choose_clusters, if result_df has less than 3 pathways, do not perform clustering.
  • run_pathfindR checks whether the output directory (output_dir) already exists and if it exists, now appends "(1)" to output_dir and displays a warning message. This was implemented to prevent writing over existing results.
  • in run run_pathfindR, recursive creation for the output directory (output_dir) is now supported.
  • in run run_pathfindR, if no pathways are found, the function returns an empty data frame instead of raising an error.

pathfindR 1.2

Major Changes

  • Implemented the (per subject) pathway scoring function calculate_pw_scores and the function to plot the heatmap of pathway scores per subject plot_scores.

  • Added the auto parameter to choose_clusters. When auto == TRUE (default), the function chooses the optimal number of clusters k automatically, as the value which maximizes the average silhouette width. It then returns a data frame with the cluster assignments and the representative/member statuses of each pathway.

  • Added the Fold_Enrichment column to the resulting data frame of enrichment, and as a corollary to the resulting data frame of run_pathfindR.

  • Added the option bubble to plot a bubble chart displaying the enrichment results in run_pathfindR using the helper function enrichment_chart. To plot the bubble chart set bubble = TRUE in run_pathfindR or use enrichment_chart(your_result_df).

Minor changes and bug fixes

  • Add the parameter silent_option to run_pathfindR. When silent_option == TRUE (default), the console outputs during active subnetwork search are printed to a file named "console_out.txt". If silent_option == FALSE, the output is printed on the screen. Default was set to TRUE because multiple console outputs are simultaneously printed when running in parallel.

  • Added the list_active_snw_genes parameter to run_pathfindR. When list_active_snw_genes == TRUE, the function adds the column non_DEG_Active_Snw_Genes, which reports the non-DEG active subnetwork genes for the active subnetwork which was enriched for the given pathway with the lowest p value.

  • Added the data RA_clustered, which is the example output of the clustering workflow.

  • In the function, run_pathfindR added the option to specify the argument output_dir which specifies the directory to be created under the current working directory for storing the result HTML files. output_dir is "pathfindR_Results" by default.

  • run_pathfindR now checks whether the output directory (output_dir) already exists and if it exists, stops and displays an error message. This was implemented to prevent writing over existing results.

  • genes_table.html now contains a second table displaying the input gene symbols for which there were no interactions in the PIN.

pathfindR 1.1

Major changes

  • Added the gene_sets option in run_pathfindR to chose between different gene sets. Available gene sets are KEGG, Reactome, BioCarta and Gene Ontology gene sets (GO-BP, GO-CC and GO-MF)
  • cluster_pathways automatically recognizes the ID type and chooses the gene sets accordingly

Minor changes and bug fixes

  • Fixed issue regarding p values < 1e-13. No active subnetworks were found when there were p values < 1e-13. These are now changed to 1e-13 in the function input_processing
  • In input_processing, genes for which no interactions are found in the PIN are now removed before active subnetwork search
  • Duplicated gene symbols no longer raise an error. If there are duplicated symbols, the lowest p value is chosen for each gene symbol in the function input_processing
  • To prevent the formation of nested folders, by default and on errors, the function run_pathfindR returns to the user's working directory.
  • Citation information are now provided for our BioRxiv pre-print