CHANGELOG

0.6.2 - June 30th 2021

  • 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

0.6.1 - November 30th 2020

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

0.6.0rc - September 24th 2020

  • 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 criterion for classification of silent and intronic variants outside of splice regions (ACMG_BP7)
  • Missing ACMG 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

0.5.2 - November 18th 2019

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

0.5.1 - October 14th 2019

Fixed

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

0.5.0 - September 23rd 2019

Fixed

  • Bug in implementation of ACMG 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)