Dear Community,
Could you please share some tips on how to easily interpret CRISPRbrain information from the Open Targets platform? I find that I spend a lot of time explaining the information and conclusions for this section.
Thanks,
Shicheng
Hi Shicheng,
thanks very much for your question, which I can also interpret as a piece if feedback so I’d like to ask: is there any particular field in our CRISPRbrain widget that is harder to interpret?
To build the widget, we have prioritised genome-wide screens from the CRISPRBrain database CRISPRi/a/KO screens (healthy vs KO) to generate target-disease evidence.
The key point is that we have linked cell types to diseases, meaning these diseases are often characterised with abnormal phenotypes in these cell types - hence the association.
If knocking out a gene causes significant perturbation in the cell type, it might indicate a potential targeting strategy in the disease.
Does this help?
Best wishes,
Annalisa
Subject: Clarification on Gene Knock-Down Impact and Drug Development
Dear Annalisa,
Thank you for sharing your insights. Could we draw a more direct conclusion, such as whether gene knock-down would be beneficial for disease treatment or provide a solid indication for developing inhibitor drugs? My main goal is to correlate the direction of the effect size (positive or negative) with the drug’s mechanism of action (inhibitor or activator).
Thanks,
Shicheng
The interpretation of CRISPRbrain in the context of direction of effect would require to understand the relationship between the phenotype measured in the Contrast column and the Disease or Phenotype. For example, if we perform a CRISPR screening modulating a few genes and measuring Tau uptake in Alzheimer’s disease, we need to have a working hypothesis on how the increased or decreased Tau uptake propagates to AD’s risk vs protect.
Because we have no way to comprehensively capture this information, we decided not to include a direction of effect assessment in the Platform widget.
Does this help?
Thank you, David, for confirming. That aligns with my understanding. CRISPRi/a/KO screens require in-depth interpretation based on the study design. Given the complexity of assigning direction, the overall association score will be affected. If the direction is correctly assigned, the score will be accurate; otherwise, it may be under or overestimated.