# pathfindR 2.4.1

## Minor Changes and Bug Fixes

- fixed a bug regarding KEGG gene set fetching: removed the conversion functionality in `get_kegg_gsets()` which now returns KEGG IDs so that the user can convert the returned identifiers using a more appropriate tool (e.g. BioMart) should they wish

# pathfindR 2.4.0

## Major Changes

- implemented a new `color_kegg_pathway()` function using `ggkegg` to create colored KEGG pathway ggplot objects (instead of using `KEGGREST` to obtain the colored PNG files, which no longer works #169)
- renamed the `visualize_hsa_KEGG` function to `visualize_KEGG_diagram()` to reflect this is now able to handle KEGG pathway enrichment results from any organism
- updated the `visualize_terms()`, `visualize_term_interactions()` and `visualize_KEGG_diagram()` functions so that they now return a list of ggplot objects (named by term ID)
- updated the `get_kegg_gsets()` function to also use `ggkegg` for fetching genes per pathway data
- removed unneeded dependencies: `magick`, `KEGGgraph` and `KEGGREST`

## Minor Changes and Bug Fixes

- updated the `get_biogrid_pin()` function so that it can now determine the latest version and download/process it from BioGRID (via setting `release = "latest"`, which is now the default behavior) 

# pathfindR 2.3.1

## Minor Changes and Bug Fixes
- fixed a bug in the `UpSet_plot()` plot function regarding the interaction with `ggupset` package that was discovered in a reverse dependency check for `ggplot2 3.5.0` (#189)
- fixed gene symbol case mismatch issue in `score_terms()` (#186)
- applied enhancement suggestion from #184 to enable scale fill manual for `term_gene_graph()`

# pathfindR 2.3.0
## Major Changes
- reverted removal of `create_HTML_report()` so `run_pathfindR()` once again generates HTML reports

# pathfindR 2.2.0
## Minor Changes and Bug Fixes
- added the `disable_parallel` argument in `active_snw_enrichment_wrapper()` to be able to disable parallel runs via `foreach` 
- fixed the issue encountered on CentOS where `forech` wasn't loading `pathfindR` (#164)
- fixed a CRAN error due to a package documentation issue (#172)
- performed some refactoring and updated/improved all tests

# pathfindR 2.1.0
## Minor Changes and Bug Fixes
- removed `create_HTML_report()` so `run_pathfindR()` no longer generates a HTML report

# pathfindR 2.0.1

## Minor Changes and Bug Fixes
- added the `dir_for_report` argument in the internal function `create_HTML_report()` to fix test issues on CRAN

# pathfindR 2.0.0

## Major Changes
- updated the java active subnetwork search component and added the `seedForRandom` argument in `active_snw_search()`to ensure reproducibility. By default behavior, in `run_pathfindR()`, a seed is set for each iteration to produce reproducible results (#108)
- as the example input/output data were renamed for convenience in 'pathfindR.data' v2.0, 'pathfindR' now depends on pathfindR.data (>= 2.0) 
- refactored/simplified `run_pathfindR()`
- visualization enriched term diagrams are now NOT part of `run_pathfindR()`
- default behavior of `run_pathfindR()` is now to run in a temporary directory. The user can still set `output_dir` to run in a specified directory and also produce HTML reports
- in `hierarchical_term_clustering()`, update the sequence of number of clusters for which silhouette width is calculated for choosing the optimal number of clusters. This should speed up the function for cases with a large number of enriched terms
- updated the relevant vignettes to reflect the implemented changes

## Minor Changes and Bug Fixes
- fixed a minor issue in `return_pin_path()` where the PIN was not properly read (#157)

# pathfindR 1.6.4

## Minor Changes and Bug Fixes
- updated the alias selection function within `input_processing()` so that an alias that is not already present is selected
- updated the min-max scaling (controlled by `scale_vals`) in `color_kegg_pathway()`, the default is now `scale_vals=TRUE`
- updated the `term_gene_heatmap()` function so that legend title is shown and can be customized
- updated the `term_gene_heatmap()` function so that coloring is proper when no change values are provided in `genes_df`
- added the `sort_terms_by_p` argument to the `term_gene_heatmap()` function to enable sorting of terms by 'lowest_p'
- in visualization functions, made coloring of up-/down-regulated genes consistent (#126)
- added the `vertex.label.cex` and `vertex.size.scaling` arguments to `cluster_graph_vis()`
- added the `show_legend` argument to `visualize_term_interactions()` to toggle the legend


# pathfindR 1.6.3

## Minor Changes and Bug Fixes
- Fixed coloring issue in `color_kegg_pathway()`
- In `color_kegg_pathway()` the default value for `normalize_vals` is now `FALSE`


# 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
