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Functional Annotation of the Human Chromosome 7 鈥淢issing鈥?Proteins: A Bioinformatics Approach
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文摘
The chromosome-centric human proteome project aims to systematically map all human proteins, chromosome by chromosome, in a gene-centric manner through dedicated efforts from national and international teams. This mapping will lead to a knowledge-based resource defining the full set of proteins encoded in each chromosome and laying the foundation for the development of a standardized approach to analyze the massive proteomic data sets currently being generated. The neXtProt database lists 946 proteins as the human proteome of chromosome 7. However, 170 (18%) proteins of human chromosome 7 have no evidence at the proteomic, antibody, or structural levels and are considered 鈥渕issing鈥?in this study as they lack experimental support. We have developed a protocol for the functional annotation of these 鈥渕issing鈥?proteins by integrating several bioinformatics analysis and annotation tools, sequential BLAST homology searches, protein domain/motif and gene ontology (GO) mapping, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Using the BLAST search strategy, homologues for reviewed non-human mammalian proteins with protein evidence were identified for 90 鈥渕issing鈥?proteins while another 38 had reviewed non-human mammalian homologues. Putative functional annotations were assigned to 27 of the remaining 43 novel proteins. Proteotypic peptides have been computationally generated to facilitate rapid identification of these proteins. Four of the 鈥渕issing鈥?chromosome 7 proteins have been substantiated by the ENCODE proteogenomic peptide data.

Keywords:

human proteome project; human chromosome 7; missing proteins; sequential BLAST; functional annotation; proteotypic peptides

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