RT Journal Article
SR Electronic
T1 TIGA: Target illumination GWAS analytics
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.11.11.378596
DO 10.1101/2020.11.11.378596
A1 Jeremy J Yang
A1 Dhouha Grissa
A1 Christophe G Lambert
A1 Cristian G Bologa
A1 Stephen L Mathias
A1 Anna Waller
A1 David J Wild
A1 Lars Juhl Jensen
A1 Tudor I Oprea
YR 2021
UL http://biorxiv.org/content/early/2021/04/21/2020.11.11.378596.abstract
AB Genome wide association studies (GWAS) can reveal important genotype–phenotype associations, however, data quality and interpretability issues must be addressed. For drug discovery scientists seeking to prioritize targets based on the available evidence, these issues go beyond the single study. Here, we describe rational ranking, filtering and interpretation of inferred gene–trait associations and data aggregation across studies by leveraging existing curation and harmonization efforts. Each gene–trait association is evaluated for confidence, with scores derived solely from aggregated statistics, linking a protein-coding gene and phenotype. We propose a method for assessing confidence in gene–trait associations from evidence aggregated across studies, including a bibliometric assessment of scientific consensus based on the iCite Relative Citation Ratio, and meanRank scores, to aggregate multivariate evidence. This method, intended for drug target hypothesis generation, scoring and ranking, has been implemented as an analytical pipeline, available as open source, with public datasets of results, and a web application designed for usability by drug discovery scientists, at https://unmtid-shinyapps.net/tiga/.Competing Interest StatementCGL has a financial interest in Golden Helix Inc., a company which sells GWAS and other bioinformatics software. LJJ is one of the owners and Scientific Advisory Board members of Intomics A/S. TIO has received honoraria or consulted for Abbott, AstraZeneca, Chiron, Genentech, Infinity Pharmaceuticals, Merz Pharmaceuticals, Merck Darmstadt, Mitsubishi Tanabe, Novartis, Ono Pharmaceuticals, Pfizer, Roche, Sanofi and Wyeth. He is on the Scientific Advisory Board of ChemDiv Inc. and InSilico Medicine.