Improving GENCODE reference gene annotation using a high-stringency proteogenomics workflow

James C. Wright, Jonathan Mudge, Hendrik Weisser, Mitra P. Barzine, Jose M. Gonzalez, Alvis Brazma, Jyoti S. Choudhary () and Jennifer Harrow ()
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James C. Wright: Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton
Jonathan Mudge: Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton
Hendrik Weisser: Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton
Mitra P. Barzine: European Bioinformatics Institute, EMBL, Wellcome Genome Campus, Hinxton
Jose M. Gonzalez: Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton
Alvis Brazma: European Bioinformatics Institute, EMBL, Wellcome Genome Campus, Hinxton
Jyoti S. Choudhary: Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton
Jennifer Harrow: Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: Abstract Complete annotation of the human genome is indispensable for medical research. The GENCODE consortium strives to provide this, augmenting computational and experimental evidence with manual annotation. The rapidly developing field of proteogenomics provides evidence for the translation of genes into proteins and can be used to discover and refine gene models. However, for both the proteomics and annotation groups, there is a lack of guidelines for integrating this data. Here we report a stringent workflow for the interpretation of proteogenomic data that could be used by the annotation community to interpret novel proteogenomic evidence. Based on reprocessing of three large-scale publicly available human data sets, we show that a conservative approach, using stringent filtering is required to generate valid identifications. Evidence has been found supporting 16 novel protein-coding genes being added to GENCODE. Despite this many peptide identifications in pseudogenes cannot be annotated due to the absence of orthogonal supporting evidence.

Date: 2016
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DOI: 10.1038/ncomms11778

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