title: Cross-tissue Analysis of Gene and Protein Expression in Normal and Cancer Tissues.
abstract: The central dogma of molecular biology describes the translation of genetic information from mRNA to protein, but does not specify the quantitation or timing of this process across the genome. We have analyzed protein and gene expression in a diverse set of human tissues. To study concordance and discordance of gene and protein expression, we integrated mass spectrometry data from the Human Proteome Map project and RNA-Seq measurements from the Genotype-Tissue Expression project. We analyzed 16,561 genes and the corresponding proteins in 14 tissue types across nearly 200 samples. A comprehensive tissue- and gene-specific analysis revealed that across the 14 tissues, correlation between mRNA and protein expression was positive and ranged from 0.36 to 0.5. We also identified 1,012 genes whose RNA and protein expression was correlated across all the tissues and examined genes and proteins that were concordantly and discordantly expressed for each tissue of interest. We extended our analysis to look for genes and proteins that were differentially correlated in cancer compared to normal tissues, showing higher levels of correlation in normal tissues. Finally, we explored the implications of these findings in the context of biomarker and drug target discovery.
authors.affiliation: Institute for Computational Health Sciences, University of California, San Francisco, California, United States of America.
authors.forename: Idit
authors.initials: I
authors.lastname: Kosti
authors.affiliation: Institute for Computational Health Sciences, University of California, San Francisco, California, United States of America.
authors.forename: Nishant
authors.initials: N
authors.lastname: Jain
authors.affiliation: Institute for Computational Health Sciences, University of California, San Francisco, California, United States of America.
authors.forename: Dvir
authors.initials: D
authors.lastname: Aran
authors.affiliation: Institute for Computational Health Sciences, University of California, San Francisco, California, United States of America.
authors.forename: Atul J
authors.initials: AJ
authors.lastname: Butte
authors.affiliation: Institute for Computational Health Sciences, University of California, San Francisco, California, United States of America.
authors.forename: Marina
authors.initials: M
authors.lastname: Sirota
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D016208:Databases, Factual; D005786:Gene Expression Regulation; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D025341:Principal Component Analysis; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D001743:Urinary Bladder / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; D020543:Proteome; D012333:RNA, Messenger