CRISPR data score calculation/integration and how about si-shRNA?

Hi again :blush:,

If we understand correctly, the CRISPR data done by the Sanger ‘Score’ project is somehow incorporated in the ‘Pathways & systems biology’ score. Could we have a bit more information about ‘how’ it is calculated and reported (we saw the famous 41.5 threshold but not sure about what does that mean :blush: btw, is it the target priority score and not the fitness score ?) ?

Also, a question rise about why choose the Sanger CRISPR data and not the siRNA or shRNA data, as well reported in DepMap ? (because of ‘quality’/’trust’ of the data?)

Thanks!

Cheers

Nicolas

Dear Nicolas,

The CRISPR data currently integrated into the Platform is part of the Open Targets project that resulted in the Sanger Project Score. The main results as well as the analysis were described in Behan et al. (Nature, 2019).

A big part of the study focuses on the interpretation of the synthetic-lethal scores in the context of drug discovery. The research article resulted in a pipeline that generates the priority score. In the platform, we incorporated the results and accepted the 41.5 thresholds implemented by the authors. Scores are then divided by 100 to build evidence scores between 0 and 1, but original scores are presented on our evidence page (WRN - colorectal).

Regarding the inclusion of other datasets, we are open to other datasets that might be of interest to the community, provide potentially causal links between targets and diseases, and we can comply with the license. We would probably prioritise CRISPR over si/shRNA, but we could eventually accommodate any data with the appropriate scoring schemes.

We are currently in the process of integrating some other CRISPR studies from Open Targets Projects that would only be available to partners in the first place, but eventually will be available to the whole community.

I hope this helps to understand the logic behind some of our decisions

David