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

Author

Listed:
  • 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)

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.

Suggested Citation

  • James C. Wright & Jonathan Mudge & Hendrik Weisser & Mitra P. Barzine & Jose M. Gonzalez & Alvis Brazma & Jyoti S. Choudhary & Jennifer Harrow, 2016. "Improving GENCODE reference gene annotation using a high-stringency proteogenomics workflow," Nature Communications, Nature, vol. 7(1), pages 1-11, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11778
    DOI: 10.1038/ncomms11778
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