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relevant genes differentially expressed in cases vs controls

Role of target pathway in disease pathophysiology for pre-clinical molecule

SUMMARY
An early stage biotech had animal model data for a novel target and wanted to confirm with in-human genomics
Scientific Question
The client wished to validate the relationship of a metabolic pathway to the pathophysiology of PAH by identifying both genetic variants and differential expression in 79 ‘genes of interest’ relevant to given pathway (selected in collaboration with the client) in PAH patients compared to controls matched on age, sex, and smoking status
Evidence Triaxia Provided
TriAxia extracted a cross-center cohort of PAH patients (confirmed by hemodynamics) with demographic, clinical and molecular (WES, RNA Expression) data as well as a set of the same data for healthy controls from the same health systems (to correct for batch effects)

We then compared the cases to controls across the 79 genes of interest for both presence of variants and relative strength of expression
Results
64 of the 79 genes of interest had statistically significant variation in expression and or presence of variance between the cases and the controls

In other words, there was evidence of the role of the pathway in the pathophysiology of PAH, and the clinical trial was funded and launched

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