Skip to contents

Changelog

Source: vignettes/CHANGELOG.Rmd
CHANGELOG.Rmd

v2.3.0

  • Date: 2026-06-22

  • Major data updates

    • ClinVar (2026-06)
    • dbNSFP (v5.3)
    • CIViC (2026-06-20)
    • GENCODE v49 (VEP v115)

  • Variant classification updates

    • Complete revision and much simplified implementation for ACMG/AMP variant classification, still point-based, but more coherent to criteria outlined in ClinGen’s Criteria Specification Registry, considering e.g. 
      • gene-specific allele frequency thresholds for different criteria (BA1/BS1/PM2/PM1/PM4)
      • Not relying on allele frequencies from one specified subpopulation, but rather considering all frequencies across gnomAD subpopulations (groupmax approach, as recommended by ClinGen SVI working group)
      • PM2 supporting not given weight in accumulating pathogenicity score due to limited evidence for pathogenicity by mere rarity
      • refined handling of PVS1 criterion for loss-of-function (LOF) variants according to PVS1 decision tree
      • revised MaxEntScan (MES) thresholds for LOF variants in the neighbourhood of canonical splice donor/acceptor sites.
    • All virtual panel genes in HTML report display in alphabetic order, ignoring confidence levels (PanelApp genes)
    • New column ACMG_CODE in TSV output files, indicating which ACMG criteria that were met for each variant (‘|’-separated list)
    • Renamed column CPSR_CLASSIFICATION_SOURCE → ASSERTION_AUTHORITY in TSV output to better reflect its role (values: ClinVar or CPSR)
    • Renamed column CANCER_PHENOTYPE to CLINVAR_PHENOTYPE_CANCER in TSV output, to clarify that this annotation is based on ClinVar phenotype associations
    • Added new column ASSERTION_RATIONALE in TSV output, providing a human-readable explanation for why a given assertion authority was chosen (e.g. “Novel variant (absent from ClinVar)”, “ClinVar review status: 2 gold stars”, “Conflicting ClinVar interpretations”)
    • Simplified population allele frequency arguments for variant classification:
      • Removed --pop_gnomad (previously required to select a single gnomAD subpopulation, e.g. nfe) and --maf_upper_threshold (global MAF filter)
      • Replaced by a single argument --max_af_gnomad, which applies an upper frequency threshold across all gnomAD subpopulations rather than one selected population — consistent with the ClinGen SVI groupmax approach already used internally for BA1/BS1/PM2 criteria
    • New argument --clinvar_trust_level (integer, 0–4) replacing --classify_all, giving fine-grained control over the degree to which existing ClinVar classifications override CPSR’s own ACMG/AMP result:
      • 0: ClinVar fully trusted; CPSR only overrides conflicted records (default)
      • 1: CPSR overrides zero gold star ClinVar records
      • 2: CPSR overrides zero- and single gold star ClinVar records
      • 3: CPSR overrides low-star and non-cancer-phenotype ClinVar records
      • 4: CPSR always classifies, ClinVar records never take precedence

  • Interactive HTML report tables migrated from DT (DT::datatable) to reactable (reactable::reactable):

    • All classification, secondary findings, pharmacogenomics, biomarker, and GWAS variant tables now use reactable

  • Tables feature a collapsible detail row per variant with full annotation context, reducing visual clutter in the main view

  • Dedicated hidden search index column aggregates nested evidence text fields (HTML biomarker tables) for full-text search across all evidence items

  • Excel workbook — SETTINGS and DATA_VERSIONS sheets

    • Two new sheets are prepended to the Excel workbook output (.xlsx), before VIRTUAL_PANEL:
      • SETTINGS — key run parameters in a three-column SECTION / PARAMETER / VALUE layout, covering: CPSR/PCGR versions, genome assembly, sample ID, variant classification settings (gnomAD MAF threshold, ClinVar trust level, secondary findings, pharmacogenomics findings, GWAS hits, noncoding filter), and VEP settings (transcript set, pick order)
      • DATA_VERSIONS — one row per reference dataset used in the run, with columns DATABASE / VERSION / DESCRIPTION / URL / LICENSE; mirrors the “Dataset versions” callout in the HTML Documentation section

  • Infrastructure: major refactor of GitHub Actions workflow

    • moving to gitflow development mode, with main branch for stable releases, and dev branch for development
    • switch to rattler-build from conda mambabuild
      • also requires moving to the required rattler format for the conda recipe
    • switch to conda-incubator/setup-miniconda (from mamba-org/setup-micromamba)
    • pkgdown’s auto development mode allows us to keep a dev website with documentation for the latest development version of cpsr, which is now available at https://sigven.github.io/cpsr/dev/ (previously only stable versions were available on the website)

v2.2.5

  • Date: 2025-09-17
  • Patch to safeguard missing gnomAD frequencies in the non-cancer subset, using the general/global gnomAD frequencies as a fallback - improved assignment of ACMG criteria BA1/BS1/PM2
    • Supplement gnomAD exome AFs with genome-based AF’s when running in VEP, i.e. adding the --af_gnomadg by default
    • Added interactive filtering for global gnomAD frequencies in HTML datatables
    • Added gnomADg_AF (global gnomAD MAF) column in TSV output files

v2.2.4

  • Date: 2025-09-08
  • Patch to avoid duplicate matches of PVS1 criteria

v2.2.1

  • Date: 2025-03-23
  • Patch to fix bug with non-standard ClinVar significance levels (Drug Response, Risk Factor)

v2.2.0

  • Date: 2025-03-22
  • Major data updates
    • ClinVar (2025-03)
    • dbNSFP (v5.0)
    • CIViC (2025-03-13)
    • GENCODE v47 (VEP v113)
    • PanelApp (2025-02)
    • UniProt KB (2025-01)
    • Cancer Gene Census (v101)
  • Added more cancer susceptibility genes to panel zero (ATG12, BIK, CHD1L, CMTR2, CPAP, HAVCR2, LLGL2, MYO3A, MYO5B, PAH, TTC7A)
  • Added a pharmacogenetic findings option (--pgx_findings), which will include pharmacogenetic findings in the HTML report (within the Genomic biomarkers section)
    • For now, this is implemented very simple, not considering star alleles, but merely focusing on pathogenic variants or drug-response related variants in DPYD, TPMT, and NUDT15
  • Two new TSV output files: <sample_id>.cpsr.<genome_assembly>.pgx_findings.tsv.gz and <sample_id>.cpsr.<genome_assembly>.biomarker_evidence.tsv.gz
  • Cleaned the display of virtual panel genes in Excel output, added PHARMACOGENETIC_FINDINGS sheet
  • Multiple cosmetic changes to HTML report - e.g. collapsed call-out blocks
  • Improved the variant classification algorithm
    • addition of new criterion: disruption of essential nucleotides (ACMG_PM6)
    • improved matching against pathogenic/benign codons (ClinVar)

v2.1.2

v2.1.1

  • Date: 2024-10-11

  • Cosmetic fixes in HTML report

v2.1.0

  • Date: 2024-09-29
  • Major data updates
    • ClinVar (2024-09)
    • dbNSFP (v4.8)
    • CIViC (2024-09-18)
  • Adjusted thresholds for CPSR variant classification based on calibration against ClinVar (Sept 2024 release)
  • Added link to chosen virtual panel in HTML report
  • Created new column ALTERATION in variant tables of HTML report, a joint annotation of HGVSp and HGVSc

v2.0.3

  • Date: 2024-08-01
  • Fixed bug for properly copying in quarto templates

v2.0.1

  • Date: 2024-07-07
  • Fixed bug for chrM variants in input - not properly annotated by VEP, and not correctly processed in pcgrr. Any mitochondrial variants found in input VCF are now removed during VCF pre-processing.

v2.0.0

  • Date: 2024-06-26
  • Data updates
    • ClinVar
    • GWAS catalog
    • CIViC
    • GENCODE
    • Cancer Gene Census
    • PanelApp
    • Disease Ontology/EFO
    • UniProt KB
Added/changed
  • New report generation framework - quarto
    • multiple options related to Rmarkdown output are now deprecated
  • Re-organized data bundle structure
    • Users need to download an assembly-specific VEP cache separately from PCGR/CPSR, and provide its path to the new required argument --vep_dir in the cpsr command
  • Re-engineered data bundle generation pipeline
  • Improved data bundle documentation
    • An HTML report with an overview of the contents of the data bundle is shipped with the reference data itself, also available here (grch38).
  • Cleaned up code base for reporting and classification
  • A multi-sheet Excel workbook output with variant classifications and biomarker findings are provided, suitable e.g. for aggregation of results across samples
  • Singularity/Apptainer support
  • argument name changes to cpsr:
    • --pcgr_dir is now named --refdata_dir
    • --clinvar_ignore_noncancer is now named --clinvar_report_noncancer, meaning that variants found in ClinVar, yet attributed to non-cancer related phenotypes, are now excluded from reporting by default)
    • --vep_gencode_all is now named --vep_gencode_basic, meaning that the gene variant annotation is now using all GENCODE transcripts by default, not only the basic set)
    • --preserved_info_tags is now named --retained_info_tags
    • --basic is now named --no_reporting
  • LOFTEE plugin in VEP removed as loss-of-function variant classifier (due to low level of maintenance, and outdated dependency requirements). For now, a simplified LoF-annotation is used as a replacement, looking primarily at CSQ types (stop_gained, frameshift_variant, splice_acceptor_variant, splice_donor_variant). Furthermore, frameshift/stop-gain variants that are found within the last 5% of the coding sequence length are deemed non-LOF, as are splice donor variants not disrupting the canonical site (GC>GT). An even more advanced LoF-annotation is planned for a future release.
  • Biomarkers are matched much more comprehensively than in previous versions, matching at the genomic level, codon, exon, amino acid and gene level (both principal and non-principal transcript matches)
  • Some bugs in the retrieval of secondary variant findings have been fixed
Removed
  • Options for configuring Rmarkdown output, i.e. --report_theme, report_nonfloating_toc, report_table_display argument in the cpsr command is deprecated
  • --gwas_p_value
  • --no_vcf_validate - VCF validation is simplified, not relying on the strict vcf-validator

v1.0.1

  • Date: 2022-11-11
Added
  • Logo

v1.0.0

  • Date: 2022-02-25

  • Data updates

    • ClinVar
    • GWAS catalog
    • CIViC
    • CancerMine
    • KEGG
    • Disease Ontology/EFO
    • Open Targets Platform,
    • UniProt KB
    • GENCODE

  • Improved detection of secondary variant findings

  • CPSR is now implemented as a dedicated R package, depending also on the pcgrr R package. Running the complete CPSR workflow relies upon installation of PCGR.

v0.6.2

  • Date: 2021-06-30

  • Data updates: ClinVar, PanelApp, GWAS catalog, CIViC, CancerMine, dbNSFP, KEGG, Disease Ontology/EFO, Open Targets Platform, UniProt KB, GENCODE

  • Software upgrades: R v4.1, Bioconductor v3.13, VEP (104) ++

  • Improved GWAS track for cancer phenotypes

Changed
  • TOML-based configuration for CPSR is abandoned, all options to CPSR are now configured through the command-line parameters
Added

  • Command-line options

    • Previously set in TOML file
      • --pop_gnomad
      • --report_theme
      • --preserved_info_tags (previously custom_tags (TOML))
      • --custom_list_name
      • --gwas_p_value
      • --vcfanno_n_proc (previously n_vcfanno_proc (TOML))
      • --vep_n_forks (previously n_vep_forks (TOML))
      • --vep_pick_order
      • --vep_no_intergenic (previously vep_skip_intergenic (TOML))
    • New options
      • --report_nonfloating_toc (NEW) - add the TOC at the top of the HTML report, not floating at the left of the document
      • --report_table_display (NEW) - choose level of comprehensiveness in interactive data tables (full versus light (default))

  • Improved support for noncoding variant interpretation, primarily in the context of variants of uncertain significance (VUS). Annotations will show variants that disrupt/create microRNA target sites (dbMTS), and variants that overlap transcription factor binding sites (critical and non-critical positions). Genomic conservation scores (GERP) are also provided.

  • Approx. 100 protein-coding genes have been appended to the CPSR superpanel (panel 0)

Fixed
Removed
  • Command-line Options
    • --conf - configuration file

v0.6.1

  • Date: 2020-11-30
Added
  • Increased number of genes in panel 0: All genes in 42 virtual panels related to cancer conditions in Genomics England PanelApp now also contributes toward panel 0
  • Added option in main script (--clinvar_ignore_noncancer) that will exclude any query variants (from HTML report and TSV/JSON output) that have been reported and classified for non-cancer related conditions only (in ClinVar)
    • this to exclude variants associated with non-cancer related phenotypes
  • For the variant biomarker table, the resolution of the reported biomarker mapping is highlighted with designated background colors for the gene (exact/codon - black vs. exon/gene - orange)
Fixed
  • Bug in GWAS hits retrieval, Issue #30
  • Custom VCF tags (as specified by user in configuration file) not shown in output TSV files
Changed
  • Removed DisGeNET annotations from output (associations from Open Targets Platform serve same purpose)
  • Renamed report section Genomic Biomarkers to Variant Biomarkers
  • Option --incidental_findings changed back to --secondary_findings - recommended term to use according to ACMG
  • Removed MOD (mechanism-of-disease) from TSV output file

v0.6.0rc

  • Date: 2020-09-24

  • Data updates: ClinVar, GWAS catalog, GENCODE, CIViC, CancerMine, UniProt KB, dbNSFP, Pfam, KEGG, Open Targets Platform, Genomics England PanelApp

  • Software updates: VEP 101

Fixed
  • Duplicated entries in incidental findings
Changed
  • All arguments to cpsr.py are now non-positional
  • Arguments to cpsr.py are divided into two groups: required and optional
  • secondary_findings is now coined incidental_findings
  • Option gwas:gwas_hits in CPSR configuration file is now optional argument --gwas_findings in cpsr.py
  • Option classification:clinvar_cpsr in CPSR configuration file is now optional argument --classify_all in cpsr.py
  • Option maf_imits:maf_gnomad in CPSR configuration file is now optional argument --maf_upper_threshold in cpsr.py
  • Option secondary_findings:show_sf in CPSR configuration file is now optional argument --incidental_findings in cpsr.py
  • Virtual panels is now displayed through HTML (previously static ggplot plot)
  • Settings section of report is now divived into three:
    • Sample metadata
    • Report configuration
    • Virtual panel
  • Classifications of genes as tumor suppressors/oncogenes are now based on a combination of CancerMine citation count and presence in Network of Cancer Genes
Added
  • Missing ACMG/AMP criterion for classification of silent and intronic variants outside of splice regions (ACMG_BP7)
  • Missing ACMG/AMP criterion for classification of variants in promoter and untranslated regions (ACMG_BP3)
  • Possibility to create custom virtual panel - any combination of genes from panel 0 provided as a single-column text file with argument --custom_list
  • Ensured that non-empty datatables pr. tier (ClinVar and Non-ClinVar) are set as the active tab
  • Improved documentation of variant classification in the References section
  • DOIs available for all references

v0.5.2

  • Date: 2019-11-18
Changed
  • Definition of pathogenic range (wrt to variant frequency) takes into account population- and position-specific allele numbers - no longer defined only by allele counts (i.e. AC) but by AC and AN
  • Moved virtual panel identifier from positional argument to optional argument (--panel_id) in cpsr.py
Added
  • Ability to analyze custom panels, provided through option --custom_panel. Needs to be defined as BED file with four columns, i.e. chromosome, start, stop, genesymbol

v0.5.1

  • Date: 2019-10-14
Fixed
  • Bug in cpsr_validate_input.py, GitHub Issue
  • Bug when there are zero variants with a ‘PASS’ status in VCF - omitting report generation

v0.5.0

  • Date: 2019-09-23
Fixed
  • Bug in implementation of ACMG/AMP criteria; genes without a known loss-of-function mechanism were handled inappropriately
  • Bug in assignment of heterozygous/homozygous states (input VCF)
  • Bug in implementation of ACMG_PS1 - Same amino acid change as previously pathogenic variant
  • Improved consequence prioritisation for variants with transcript consequences in multiple, distinct cancer predisposition genes
  • Upper MAF threshold (as given by user) only applied for unclassified (i.e. non-ClinVar variants)
  • Handling of non-coding variants (synonymous, upstream_variants) in the report, no longer excluded
Added
  • Section on genomic biomarkers; indicating which variants in the query VCF that overlaps with existing germline biomarkers (CIViC)