biostudies-literatureAryal SNational Center for Research ResourcesNational Eye InstituteNEI NIH HHSNCRR NIH HHSNCI NIH HHSNational Institutes of HealthNational Institute of General Medical SciencesNIH HHSNIGMS NIH HHS151-184https://www.ebi.ac.uk/biostudies/studies/S-EPMC6983357biostudies-literatureUnknown139(2)While the bioinformatics resource-tool iSyTE (integrated Systems Tool for Eye gene discovery) effectively identifies human cataract-associated genes, it is currently based on just transcriptome data, and thus, it is necessary to include protein-level information to gain greater confidence in gene prioritization. Here, we expand iSyTE through development of a novel proteome-based resource on the lens and demonstrate its utility in cataract gene discovery. We applied high-throughput tandem mass spectrometry (MS/MS) to generate a global protein expression profile of mouse lens at embryonic day (E)14.5, which identified 2371 lens-expressed proteins. A major challenge of high-throughput expression profiling is identification of high-priority candidates among the thousands of expressed proteins.Human geneticsMS/MS in silico subtraction-based proteomic profiling as an approach to facilitate disease gene discovery: application to lens development and cataract.PMC6983357S10 RR027273S10OD-012246P20 GM103446P30 CA069533P30 EY010572R01 EY021505R01 EY029770S10 OD012246David LLAryal SHernandez FGHuang HWilmarth PAAnand DReddy APWeatherbee BATLachke SAfalseMS/MS in silico subtraction-based proteomic profiling as an approach to facilitate disease gene discovery: application to lens development and cataract.While the bioinformatics resource-tool iSyTE (integrated Systems Tool for Eye gene discovery) effectively identifies human cataract-associated genes, it is currently based on just transcriptome data, and thus, it is necessary to include protein-level information to gain greater confidence in gene prioritization. Here, we expand iSyTE through development of a novel proteome-based resource on the lens and demonstrate its utility in cataract gene discovery. We applied high-throughput tandem mass spectrometry (MS/MS) to generate a global protein expression profile of mouse lens at embryonic day (E)14.5, which identified 2371 lens-expressed proteins. A major challenge of high-throughput expression profiling is identification of high-priority candidates among the thousands of expressed proteins.2020-01-01T00:00:00Z2020 Feb2026-04-07T23:04:23.959Z2021-02-21T05:14:01ZS-EPMC69833573179704910.1007/s00439-019-02095-5