Integrated transcriptomic-proteomic analysis using a proteogenomic workflow refines rat genome annotation

Kumar, Dhirendra, Yadav, Amit Kumar, Jia, Xinying, Mulvenna, Jason and Dash, Debasis (2016) Integrated transcriptomic-proteomic analysis using a proteogenomic workflow refines rat genome annotation. Molecular and Cellular Proteomics, 15 1: 329-339. doi:10.1074/mcp.M114.047126


Author Kumar, Dhirendra
Yadav, Amit Kumar
Jia, Xinying
Mulvenna, Jason
Dash, Debasis
Title Integrated transcriptomic-proteomic analysis using a proteogenomic workflow refines rat genome annotation
Journal name Molecular and Cellular Proteomics   Check publisher's open access policy
ISSN 1535-9484
1535-9476
Publication date 2016-01-01
Year available 2016
Sub-type Article (original research)
DOI 10.1074/mcp.M114.047126
Open Access Status Not Open Access
Volume 15
Issue 1
Start page 329
End page 339
Total pages 11
Place of publication Rockville, United States
Publisher American Society for Biochemistry and Molecular Biology
Language eng
Subject 1602 Analytical Chemistry
1303 Biochemistry
1312 Molecular Biology
Abstract Proteogenomic re-annotation and mRNA splicing information can lead to the discovery of various protein forms for eukaryotic model organisms like rat. However, detection of novel proteoforms using mass spectrometry proteomics data remains a formidable challenge. We developed EuGenoSuite, an open source multiple algorithmic proteomic search tool and utilized it in our in-house integrated transcriptomic-proteomic pipeline to facilitate automated proteogenomic analysis. Using four proteogenomic pipelines (integrated transcriptomic-proteomic, Peppy, Enosi, and ProteoAnnotator) on publicly available RNA-sequence and MS proteomics data, we discovered 363 novel peptides in rat brain microglia representing novel proteoforms for 249 gene loci in the rat genome. These novel peptides aided in the discovery of novel exons, translation of annotated untranslated regions, pseudogenes, and splice variants for various loci; many of which have known disease associations, including neurological disorders like schizophrenia, amyotrophic lateral sclerosis, etc. Novel isoforms were also discovered for genes implicated in cardiovascular diseases and breast cancer for which rats are considered model organisms. Our integrative multi-omics data analysis not only enables the discovery of new proteoforms but also generates an improved reference for human disease studies in the rat model.
Formatted abstract
Proteogenomic re-annotation and mRNA splicing information can lead to the discovery of various protein forms for eukaryotic model organisms like rat. However, detection of novel proteoforms using mass spectrometry proteomics data remains a formidable challenge. We developed EuGenoSuite, an open source multiple algorithmic proteomic search tool and utilized it in our in-house integrated transcriptomic-proteomic pipeline to facilitate automated proteogenomic analysis. Using four proteogenomic pipelines (integrated transcriptomic-proteomic, Peppy, Enosi, and ProteoAnnotator) on publicly available RNA-sequence and MS proteomics data, we discovered 363 novel peptides in rat brain microglia representing novel proteoforms for 249 gene loci in the rat genome. These novel peptides aided in the discovery of novel exons, translation of annotated untranslated regions, pseudogenes, and splice variants for various loci; many of which have known disease associations, including neurological disorders like schizophrenia, amyotrophic lateral sclerosis, etc. Novel isoforms were also discovered for genes implicated in cardiovascular diseases and breast cancer for which rats are considered model organisms. Our integrative multi-omics data analysis not only enables the discovery of new proteoforms but also generates an improved reference for human disease studies in the rat model.
Keyword Biochemical Research Methods
Biochemistry & Molecular Biology
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID BSC-0121
Institutional Status Non-UQ

 
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