Functional Annotation of the Human Chromosome 7 “Missing” Proteins: A Bioinformatics Approach

Abstract

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 "missing" in this study as they lack experimental support. We have developed a protocol for the functional annotation of these "missing" 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 "missing" 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 "missing" chromosome 7 proteins have been substantiated by the ENCODE proteogenomic peptide data.

Accelerating the search for the missing proteins in the human proteome

“…Under the C-HPP, the proteomic information found across chromosomes 1-22, X, Y and mitochondrial DNA are being studied by country-based or regional cluster teams. Australia and New Zealand undertook analysis of the proteins coded by human chromosome 7 (Chr 7) 24 25 . As part of our ongoing efforts, we demonstrate that current PE2-4 proteins are located across the length of the long and short arms, approximately equally dispersed across the length of Chr 7 ( Fig.…”

Clinical implications of recent advances in proteogenomics

“…The latest one-shot extensive draft map of the human proteome validated 17,294 genes, accounting for 84% of annotated protein-coding genes [55]. Further analysis of large shotgun proteomic datasets resulted in a better annotation of specific human subproteomes: the mitochondrial proteome [33], hippocampus and brain proteome [56,57], liver proteome [58], and spermatozoan proteome [59], as well as several human chromosomes: chromosome 1 [60], chromosomes 2 and 14 [61], chromosome 4 [62], chromosome 7 [63], chromosome 9 [64], chromosome 12 [65,66], chromosome 16 [67], chromosome 17 [68], chromosome 18 [69,70], and chromosome 22 [71]. Table 1 lists the main outcomes of these studies.…”

Genome-wide Proteomics, Chromosome-centric Human Proteome Project (C-HPP), Part II

“…In the January 2013 issue, there were 22 papers from C-HPP teams on the following subjects: 13 articles from chromosome teams 1,4,7,8,11,13,16,17,18,19, 20, X, and Y; database reports (including neXtProt, PeptideAtlas, and CAPER); technology papers; and cross-cutting articles (from the C-HPP and B/D-HPP leadership and the HUPO Industrial Advisory Board). There were 11 additional articles stimulated by the announcement of the Special Issue, which were related to the C-HPP.…”

“…In the first year of the C-HPP consortium, we have observed visible funding seed money increases in several countries including China (Chr. 1,8,20), Iran (Chr. Y), Canada (Chr.…”