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Impact of proteogenomic evidence on clinical success

Karim, M. A.; Hukku, A.; Ariano, B.; Holzinger, E.; Tsepilov, Y.; Hayhurst, J.; Buniello, A.; McDonagh, E. M.; Castel, S. E.; Nelson, M. R.; Maranville, J.; Yerges-Armstrong, L.; Ghoussaini, M.

2026-02-25 genetic and genomic medicine
10.64898/2026.02.23.26346731 medRxiv
Show abstract

We assessed the impact of plasma protein quantitative trait loci (pQTL) on therapeutic hypotheses backed by human genetic evidence. We show that pQTL-supported target-indication pairs were 4.7 times more likely to advance from Phase I to launch, compared to a 2.6-fold increase observed only with human genetic evidence. Moreover, pQTL-based enrichment was prominent in druggable protein families which had limited enrichment from human genetic evidence alone.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.