Systematically Identifying And Dissecting The Human Secreted Proteins With Integrative Multi-omics Data

Secreted proteins(SPs)play important roles in diverse biological processes including maintaining cell-cell communication,controlling proliferation,regulating metabolism and immune response,which are crucial for monitoring health status.Although some studies have explored the human SPs,the credibility of previous SP results and the result consistency between different studies are low.This largly hinders the.subsequent analysis of human SPs.Moreover,with the rapid development of genomics and proteomics,a large number of novel proteins have been identified which may contain novel SPs.In addition,with the continuous improvement of computational approaches and priori knowledges,the accuracy of tools used for SP prediction and analysis is much improved as well.Thus it is necessary to integrate multi-omics data to systematically identify the highly reliable human SPs and dissect their characteristics.Here we identified 6,943 high-quality human SPs through a series of computational analyses based on 330,427 human proteins derived from the databases of UniProt,Ensembl,AceView and RefSeq.Strikingly,3,522 SPs are characterized as novel since they are not contained in other SP databases.By analyzing a large amount of mass spectrometry and RNA-seq data as well as investigating various databases,we found that 6,267 of those 6,943(90:3%)SPs have the supporting evidences at protein and/or transcript levels.These SPs were expressed in diverse human tissues and a significant fraction of them exhibited tissue-specific expression.Interestingly,' 1,692 SPs were detected in human body fluid including plasma,urine and cerebrospinal fluid.Moreover,89.21%of those 6,943 SPs were annotated with known protein domains.Importatnly,we developed a user friendly database,SPRomeDB(http://www.megabionet.org:8080/SPRomeDB/),to provide those various useful information of human SPs.Collectively,our comprehensive identification and characterization of the human secretome gain insights into human SPs and provide valuable resource.