Comprehensive Identification and Characterization of Human Secretome Based on Integrative Proteomic and Transcriptomic Data

Geng Chen; Jiwei Chen; Huanlong Liu; Shuangguan Chen; Yang Zhang; Peng Li; Danielle Thierry-Mieg; Jean Thierry-Mieg; William Mattes; Baitang Ning; Tieliu Shi

doi:10.3389/fcell.2019.00299

Comprehensive Identification and Characterization of Human Secretome Based on Integrative Proteomic and Transcriptomic Data

Front Cell Dev Biol. 2019 Nov 21:7:299. doi: 10.3389/fcell.2019.00299. eCollection 2019.

Authors

Affiliations

¹ The Center for Bioinformatics and Computational Biology, Shanghai Key Laboratory of Regulatory Biology, The Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
² National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, United States.
³ National Center for Toxicological Research, Food and Drug Administration, Jefferson City, AR, United States.

Abstract

Secreted proteins (SPs) play important roles in diverse important biological processes; however, a comprehensive and high-quality list of human SPs is still lacking. Here we identified 6,943 high-confidence human SPs (3,522 of them are novel) based on 330,427 human proteins derived from databases of UniProt, Ensembl, AceView, and RefSeq. Notably, 6,267 of 6,943 (90.3%) SPs have the supporting evidences from a large amount of mass spectrometry (MS) and RNA-seq data. We found that the SPs were broadly expressed in diverse tissues as well as human body fluid, and a significant portion of them exhibited tissue-specific expression. Moreover, 14 cancer-specific SPs that their expression levels were significantly associated with the patients' survival of eight different tumors were identified, which could be potential prognostic biomarkers. Strikingly, 89.21% of 6,943 SPs (2,927 novel SPs) contain known protein domains. Those novel SPs we mainly enriched with the known domains regarding immunity, such as Immunoglobulin V-set and C1-set domain. Specifically, we constructed a user-friendly and freely accessible database, SPRomeDB (www.unimd.org/SPRomeDB), to catalog those SPs. Our comprehensive SP identification and characterization gain insights into human secretome and provide valuable resource for future researches.

Keywords: RNA-seq; human secretome; proteome; secreted proteins; transcriptome.