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Discovery of coding regions in the human genome by integrated proteogenomics analysis workflow
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
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Number of Authors: 9
2018 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, article id 903Article in journal (Refereed) Published
Abstract [en]

Proteogenomics enable the discovery of novel peptides (from unannotated genomic protein-coding loci) and single amino acid variant peptides (derived from single-nucleotide polymorphisms and mutations). Increasing the reliability of these identifications is crucial to ensure their usefulness for genome annotation and potential application as neoantigens in cancer immunotherapy. We here present integrated proteogenomics analysis workflow (IPAW), which combines peptide discovery, curation, and validation. IPAW includes the SpectrumAI tool for automated inspection of MS/MS spectra, eliminating false identifications of single-residue substitution peptides. We employ IPAW to analyze two proteomics data sets acquired from A431 cells and five normal human tissues using extended (pH range, 3-10) high-resolution isoelectric focusing (HiRIEF) pre-fractionation and TMT-based peptide quantitation. The IPAW results provide evidence for the translation of pseudogenes, lncRNAs, short ORFs, alternative ORFs, N-terminal extensions, and intronic sequences. Moreover, our quantitative analysis indicates that protein production from certain pseudogenes and lncRNAs is tissue specific.

Place, publisher, year, edition, pages
2018. Vol. 9, article id 903
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Biological Sciences Medicinal Chemistry
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URN: urn:nbn:se:su:diva-154630DOI: 10.1038/s41467-018-03311-yISI: 000426469900005PubMedID: 29500430OAI: oai:DiVA.org:su-154630DiVA, id: diva2:1194715
Available from: 2018-04-03 Created: 2018-04-03 Last updated: 2018-04-03Bibliographically approved

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Johansson, Henrik J.Huss, MikaelVesterlund, MattiasBranca, Rui M. M.
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