A Quantitative Proteome Map of the Human Body

• Published in: Cell 2020-10, Vol.183 (1), p.269-283.e19
• Main Authors: Jiang, Lihua, Chan, Joanne, Fang, Huaying, Anand, Shankara, Gabriel, Stacey, Graubert, Aaron, Hadley, Kane, Huang, Katherine H., MacArthur, Daniel G., Meier, Samuel R., Segrè, Ayellet V., Balliu, Brunilda, Barbeira, Alvaro N., Battle, Alexis, Brown, Andrew, Brown, Christopher D., Castel, Stephane E., Conrad, Don, Cotter, Daniel J., Das, Sayantan, de Goede, Olivia M., Dermitzakis, Emmanouil T., Eskin, Eleazar, Eulalio, Tiffany Y., Garrido-Martín, Diego, Guigó, Roderic, He, Yuan, Hoffman, Paul J., Hormozdiari, Farhad, Im, Hae Kyung, Jo, Brian, Kasela, Silva, Kellis, Manolis, Kim-Hellmuth, Sarah, Li, Xin, Mohammadi, Pejman, Montgomery, Stephen B., Muñoz-Aguirre, Manuel, Nachun, Daniel C., Oliva, Meritxell, Parsana, Princy, Sabatti, Chiara, Skol, Andrew D., Stephens, Matthew, Strober, Benjamin J., Teran, Nicole A., Viñuela, Ana, Wang, Gao, Wucher, Valentin, Zou, Yuxin, Ferreira, Pedro G., Yeger-Lotem, Esti, Barcus, Mary E., Bradbury, Debra, Krubit, Tanya, McLean, Jeffrey A., Smith, Anna M., Sobin, Leslie, Tabor, David E., Brigham, Lori E., Gillard, Bryan M., Hasz, Richard, Johnson, Mark, Kopen, Gene, Moser, Michael T., Myer, Kevin, Shad, Saboor, Thomas, Jeffrey A., Washington, Michael, Rohrer, Daniel C., Valley, Dana R., Davis, David A., Mash, Deborah C., Mosavel, Maghboeba, Siminoff, Laura A., Flicek, Paul, Juettemann, Thomas, Powell, Conner C., Rosenbloom, Kate R., Ruffier, Magali, Sheppard, Dan, Taylor, Kieron, Akey, Joshua, Demanelis, Kathryn, Feinberg, Andrew P., Hansen, Kasper D., Kibriya, Muhammad G., Li, Jin Billy, Li, Qin, Linder, Sandra E., Pierce, Brandon L., Smith, Kevin S., Tang, Hua, Carithers, Latarsha J., Koester, Susan E., Little, A. Roger, Moore, Helen M., Rao, Abhi K., Vaught, Jimmie B., Volpi, Simona
• Format: Article
• Language: English
• Subjects: BBS syndrome; branched-chain amino acid metabolism; Leigh syndrome; mass spectrometry; protein and RNA correlation; quantitative proteomics; secretion; tissue-enriched or -specific proteins; TMT
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2020.08.036

Determining protein levels in each tissue and how they compare with RNA levels is important for understanding human biology and disease as well as regulatory processes that control protein levels. We quantified the relative protein levels from over 12,000 genes across 32 normal human tissues. Tissue-specific or tissue-enriched proteins were identified and compared to transcriptome data. Many ubiquitous transcripts are found to encode tissue-specific proteins. Discordance of RNA and protein enrichment revealed potential sites of synthesis and action of secreted proteins. The tissue-specific distribution of proteins also provides an in-depth view of complex biological events that require the interplay of multiple tissues. Most importantly, our study demonstrated that protein tissue-enrichment information can explain phenotypes of genetic diseases, which cannot be obtained by transcript information alone. Overall, our results demonstrate how understanding protein levels can provide insights into regulation, secretome, metabolism, and human diseases. [Display omitted] •Quantified proteins from more than 12,000 genes across 32 normal human tissues•Discordance of RNA and protein enrichment provides evidence of protein secretion•Tissue-specific distribution of enzymes indicates a coordinated control of metabolism•Tissue-enriched proteins provide insights into phenotypes of genetic diseases Proteomics analysis across human tissues from the GTeX resource reveals insight into tissue-specific pathways and phenotypes arising from genetic diseases.