Back to Search
Start Over
Chromosome-Based Proteomic Study for Identifying Novel Protein Variants from Human Hippocampal Tissue Using Customized neXtProt and GENCODE Databases.
- Source :
-
Journal of proteome research [J Proteome Res] 2015 Dec 04; Vol. 14 (12), pp. 5028-37. Date of Electronic Publication: 2015 Nov 16. - Publication Year :
- 2015
-
Abstract
- The goal of the Chromosome-Centric Human Proteome Project (C-HPP) is to fully provide proteomic information from each human chromosome, including novel proteoforms, such as novel protein-coding variants expressed from noncoding genomic regions, alternative splicing variants (ASVs), and single amino acid variants (SAAVs). In the 144 LC/MS/MS raw files from human hippocampal tissues of control, epilepsy, and Alzheimer's disease, we identified the novel proteoforms with a workflow including integrated proteomic pipeline using three different search engines, MASCOT, SEQUEST, and MS-GF+. With a <1% false discovery rate (FDR) at the protein level, the 11 detected peptides mapped to four translated long noncoding RNA variants against the customized databases of GENCODE lncRNA, which also mapped to coding-proteins at different chromosomal sites. We also identified four novel ASVs against the customized databases of GENCODE transcript. The target peptides from the variants were validated by tandem MS fragmentation pattern from their corresponding synthetic peptides. Additionally, a total of 128 SAAVs paired with their wild-type peptides were identified with FDR <1% at the peptide level using a customized database from neXtProt including nonsynonymous single nucleotide polymorphism (nsSNP) information. Among these results, several novel variants related in neuro-degenerative disease were identified using the workflow that could be applicable to C-HPP studies. All raw files used in this study were deposited in ProteomeXchange (PXD000395).
- Subjects :
- Alternative Splicing
Alzheimer Disease genetics
Amino Acid Sequence
Case-Control Studies
Chromatography, Liquid
Chromosomes, Human
Databases, Genetic
Databases, Protein
Epilepsy genetics
Genetic Variation
Hippocampus physiology
Humans
Molecular Sequence Data
Polymorphism, Single Nucleotide
Software
Tandem Mass Spectrometry
Workflow
Alzheimer Disease metabolism
Epilepsy metabolism
Hippocampus metabolism
Proteomics methods
Subjects
Details
- Language :
- English
- ISSN :
- 1535-3907
- Volume :
- 14
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of proteome research
- Publication Type :
- Academic Journal
- Accession number :
- 26549206
- Full Text :
- https://doi.org/10.1021/acs.jproteome.5b00472