Discrepancies between Hotspot / Damaging mutations (Custom Downloads) and OmicsSomaticMutations.csv (File Downloads)

Issues and Bugs
1

Hi DepMap team,

at first thank you for the great datasets and tools you are providing to the community.

I have recently observed a discrepancy between some mutation related files at depmap.org. E.g.:

  • there are several cell lines, that have Y in CosmicHotspot of OmicsSomaticMutations.csv for NRAS gene, but they have 0 value in the indicator matrix Hotspot_Mutations.csv.
  • These cell lines are
    {‘ACH-000050’,
    ‘ACH-000190’,
    ‘ACH-000220’,
    ‘ACH-000274’,
    ‘ACH-000387’,
    ‘ACH-000557’,
    ‘ACH-000810’,
    ‘ACH-000889’,
    ‘ACH-000937’,
    ‘ACH-000938’,
    ‘ACH-000994’,
    ‘ACH-002241’,
    ‘ACH-002512’}
  • also, it looks like Data Explorer of depmap.org shows only the mutations present in Hotspot_Mutations.csv, and not the ones in OmicsSomaticMutations.csv.
  • also generally there are large discrepancies between OmicsSumoaticMutations (only CosmicHotspot mutations) and Hotspot_Mutations.csv for other genes also (based on some quick check)

Could you give some information regarding these these differences? Is it related to some processing from OmicsSumoaticMutations → Hotspot_Mutations? In this case, I assume one should use the (unprocessed) OmicsSumoaticMutations file and not Hotspot_Mutations / Data Explorer? Thank you,

Bence

2

Hi Bence,

Thanks for reaching out! Currently the Hotspot mutation matrix is defined by the HessDriver column (mutations identified in this paper) in the OmicsSomaticMutations, not CosmicHotspot. You are correct that data explorer only shows hotspot mutations, and yes I would recommend using OmicsSumoaticMutations if you intend to do more comprehensive analyses.

I would also like to note that we are still in the process of updating and improving our mutation calling/annotation pipeline, and the definition of hotspots might change in the future. Please refer to our data description for the most up-to-date documentation.

Hope this helps. Sorry about the confusion!

Simone

3

Hi Simone, thank you for your answers, they made everything clear. Bests,

Bence