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Reference Mutational Signatures

COSMIC: Catalogue of Somatic Mutations in Cancer

COSMIC - Highlights

  • COSMIC displays for each signature a battery of analyses showing about tissue prevalence, strand asymmetry, enrichment
  • of histone modifications, nucleosome occupancy, CTCF occupancy, etc.

Where is this data stored in the cluster?

A tab-separated table with the COSMIC v3.4 signatures is available at: /data/bbg/datasets/COSMIC_signatures/COSMIC_v3.4_SBS_GRCh38.txt.

Key details about the data:

  • Rows: Represent the 96 possible pyrimidine-centered trinucleotide contexts.
  • Columns: Denote the respective reference signatures. Each column sums to one.
  • Cell values: Indicate the frequencies of mutations matching that context relative to the total mutations observed (i.e., the proportion of mutations matching that trinucleotide context).

Important considerations:

  • These frequencies are not equivalent to mutation rates. They were derived from whole genome samples where the reference trinucleotides are not equally represented.
  • If your study involves a different reference genome or a specific genomic region with a distinct trinucleotide content (e.g., panel sequencing), you may need to rescale the relative frequencies of the signatures accordingly.

Signature groups

As you probably know for several of the signatures in the COSMIC reference catalog there is a known aetiology, and this allows us to define several signature groups.

AlexandrovLab has defined these groups of COSMIC signatures. You can use them for your own analysis, but when running any of the tools they developed, it is very easy to filter out any of these groups in case you known that some of those exposures is not present in your samples.

See below a copy of their original table that can be found here.

Signature subgroup SBS signatures excluded DBS signatures excluded ID signatures excluded
MMR_deficiency_signatures 6, 14, 15, 20, 21, 26, 44 7, 10 7
POL_deficiency_signatures 10a, 10b, 10c, 10d, 28 3 -
HR_deficiency_signatures 3 13 6
BER_deficiency_signatures 30, 36 - -
Chemotherapy_signatures 11, 25, 31, 35, 86, 87, 90, 99 5 -
Immunosuppressants_signatures 32 - -
Treatment_signatures 11, 25, 31, 32, 35, 86, 87, 90, 99 5 -
APOBEC_signatures 2, 13 - -
Tobacco_signatures 4, 29, 92 2 3
UV_signatures 7a, 7b, 7c, 7d, 38 1 13
AA_signatures 22a, 22b 20 23
Colibactin_signatures 88 - 18
Artifact_signatures 27, 43, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 95 14 -
Lymphoid_signatures 9, 84, 85 - -

SIGNAL

  • URL: signal.mutationalsignatures.com
  • Extracted from both tumors and experimental mutagenesis assays
  • SBS, DBS and SV mutational processes
  • Maintained by the University of Cambridge

SIGNAL - Highlights

  • SIGNAL curates organ-specific signatures, consisting on typical profiles that can be realised as weighted combinations of mutational signatures at different organs. For example, here is an example of which organ-specific profiles Signature 1 contributes to depending on the tissue.