Can DepMap capture the genes which are in the synthetic lethality?

Q&A
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1

Hi, I’m interested in synthetic lethality (SL) interaction.
For the usage of DepMap data, I manually checked the genes that have SL partners such as PARP-BRCA1/2.
I assumed that due to the characteristics of SL, a specific gene and other perturbed genes (e.g., CRISPR, RNAi) have a high correlation.
But when I checked the ‘Top Co-dependency’ tab, I couldn’t confirm the PARP’s SL partner (BRCA1/2) in the DepMap data.
Which data or value can verify the SL pairs in the DepMap data?

2

PARP1 does not strongly score in genetic perturbation screens. PARP inhibitors target the PARP family, genetic screens target individual genes. I would look at the chemical perturbation data.

3

Thank you for your reply!
Then, is the individual target screening not meaningful to SL interaction?
Should I use only chemical perturbation data (e.g., PRISM drug sensitivity data)?

4

The genetic perturbation screens can be used to investigate SL interactions, however you would need to look at the individual genes in the PARP family. Alternatively, you could look at PARP inhibitors in the PRISM data.

1 Like
5

Thank you so much!
I’ll check both individual genes in PARP family and PARP inhibitors in the PRISM data.

6

Dear iboyle,

When i searched for PARP1, I got several Co-dependencies genes screened from CRISPR & RNAi in DepMap portal.
Can i consider all of these Co-dependencies genes as SL pairs for my PARP1?
Please suggest. Thanks in advance.

7

Dear Joshua,

When i searched for PARP1, I got several Co-dependencies genes screened from CRISPR & RNAi in DepMap portal.
Can i consider all of these Co-dependencies genes as SL pairs for my PARP1?
Please suggest. Thanks in advance.

8

Hi sujit123,

The dependencies of PARP1 alone are quite weak (none less than -1, most around -0.5) and further, its codependencies have a weak relationship with it (Pearson correlations < 0.3). I would hesitate to call these synthetic lethals, and instead say the data suggests a possible biological relationship between them and PARP1 which could be explored further.

9

Thank you Joshua for your suggestion.
Regards,
Sujit