When I type in a cell line, on the right there is a column Header that says “Molecular Subtypes”.
Under this it will often say “Level 0”, and under that it might say “CDKN2A-Lof”. What does Level 0 refer too? Also, how is the CDKN2A-lof (I assume loss of function) determined. In some of the cell lines I am looking at there is certainly no loss of CDKN2A mRNA and no mutations are listed. What is up with that? Thanks for your help.
I also noticed that. It is strange.
Hi,
Thanks for reaching out. We created levels to allow more granular definitions of molecular subtypes. For example, in the NRAS-mutant cell line below, “NRAS” is a level-0 subtype, while the specific NRAS mutation, Q61, is a level-1 subtype. We don’t have anything more specific for CDKN2A at the moment, so it stops at level 0. This hierarchical structure might be more relevant in our Context Explorer tool.
And to your second question, our inferred LoF status is defined as followed: LoF is True if any of the following criteria is met: WGS-based relative CN < 0.3, Likely LoF mutation with AF > 0.5, or Expression log TPM < 0.1. We often see cases where there is a deep deletion in part of the gene body, resulting in low gene-level copy number, but the remaining exons may still be expressed. We still consider this a form of LoF.
Please let me know if you have any other questions,
Simone
Hi Simone:
I’m doing a lot of work examining MTAP status in the CCLE databases. I’ve found there are several cell lines which seem to be homozygously deleted for MTAP at the DNA level, but are making substantial amounts of MTAP mRNA based on the RNAseq data. I’m trying to access the data at a more granular level using the TerraBio Workspace. I can access the was files and view them in IGV, but not the RNA seq files. Specifically the BAI files are not available. Google Gemini says they are there but “hidden”. When I tried to use IGV to view load them they appear to be there but I am not allowed access. Can you help me? I’d really like to understand how RNA can be there when the DNA is not!
Warren Kruger
Hi,
Unfortunately we don’t have index files stored for a lot of the RNAseq files, so you might need to run samtools to index them before viewing them in IGV.
This disagreement typically happens when part of the gene is homozygously deleted but the truncated transcript is still expressed and quantified. However, please let us know if you encounter any scenarios that cannot be explained by this. I’m happy to look into it.
Thanks,
Simone
