title: Quantitative and qualitative proteome characteristics extracted from in-depth integrated genomics and proteomics analysis.
abstract: Quantitative and qualitative protein characteristics are regulated at genomic, transcriptomic, and posttranscriptional levels. Here, we integrated in-depth transcriptome and proteome analyses of liver tissues from two rat strains to unravel the interactions within and between these layers. We obtained peptide evidence for 26,463 rat liver proteins. We validated 1,195 gene predictions, 83 splice events, 126 proteins with nonsynonymous variants, and 20 isoforms with nonsynonymous RNA editing. Quantitative RNA sequencing and proteomics data correlate highly between strains but poorly among each other, indicating extensive nongenetic regulation. Our multilevel analysis identified a genomic variant in the promoter of the most differentially expressed gene Cyp17a1, a previously reported top hit in genome-wide association studies for human hypertension, as a potential contributor to the hypertension phenotype in SHR rats. These results demonstrate the power of and need for integrative analysis for understanding genetic control of molecular dynamics and phenotypic diversity in a system-wide manner.
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands; Netherlands Proteomics Center, Padualaan 8, 3584 CH Utrecht, the Netherlands.
authors.forename: Teck Yew
authors.initials: TY
authors.lastname: Low
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: van Heesch
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands; Netherlands Proteomics Center, Padualaan 8, 3584 CH Utrecht, the Netherlands.
authors.forename: Henk
authors.initials: H
authors.lastname: van den Toorn
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands; Netherlands Proteomics Center, Padualaan 8, 3584 CH Utrecht, the Netherlands.
authors.forename: Piero
authors.initials: P
authors.lastname: Giansanti
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands; Netherlands Proteomics Center, Padualaan 8, 3584 CH Utrecht, the Netherlands.
authors.forename: Alba
authors.initials: A
authors.lastname: Cristobal
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Pim
authors.initials: P
authors.lastname: Toonen
authors.affiliation: Max-Delbruck-Center for Molecular Medicine (MDC), Robert-Rossle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schafer
authors.affiliation: Max-Delbruck-Center for Molecular Medicine (MDC), Robert-Rossle-Strasse 10, 13125 Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Hübner
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands; Netherlands Proteomics Center, Padualaan 8, 3584 CH Utrecht, the Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: van Breukelen
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands; Netherlands Proteomics Center, Padualaan 8, 3584 CH Utrecht, the Netherlands.
authors.forename: Shabaz
authors.initials: S
authors.lastname: Mohammed
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands. Electronic address: e.cuppen@hubrecht.eu.
authors.forename: Edwin
authors.initials: E
authors.lastname: Cuppen
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands; Netherlands Proteomics Center, Padualaan 8, 3584 CH Utrecht, the Netherlands. Electronic address: a.j.r.heck@uu.nl.
authors.forename: Albert J R
authors.initials: AJ
authors.lastname: Heck
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Victor
authors.initials: V
authors.lastname: Guryev
mesh_terms: D000818:Animals; D016678:Genome; D006973:Hypertension / Q000235:genetics; D008099:Liver / Q000378:metabolism; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D017393:RNA Editing; D012326:RNA Splicing; D051381:Rats; D011918:Rats, Inbred SHR; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D020543:Proteome; D013254:Steroid 17-alpha-Hydroxylase