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Discovery of coding regions in the human genome by integrated proteogenomics analysis workflow

Author

Listed:
  • Yafeng Zhu

    (Karolinska Institutet)

  • Lukas M. Orre

    (Karolinska Institutet)

  • Henrik J. Johansson

    (Karolinska Institutet)

  • Mikael Huss

    (Stockholm University)

  • Jorrit Boekel

    (Karolinska Institutet)

  • Mattias Vesterlund

    (Karolinska Institutet)

  • Alejandro Fernandez-Woodbridge

    (Karolinska Institutet)

  • Rui M. M. Branca

    (Karolinska Institutet)

  • Janne Lehtiö

    (Karolinska Institutet)

Abstract

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.

Suggested Citation

  • Yafeng Zhu & Lukas M. Orre & Henrik J. Johansson & Mikael Huss & Jorrit Boekel & Mattias Vesterlund & Alejandro Fernandez-Woodbridge & Rui M. M. Branca & Janne Lehtiö, 2018. "Discovery of coding regions in the human genome by integrated proteogenomics analysis workflow," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03311-y
    DOI: 10.1038/s41467-018-03311-y
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    Cited by:

    1. Eduardo Vieira de Souza & Angie L. Bookout & Christopher A. Barnes & Brendan Miller & Pablo Machado & Luiz A. Basso & Cristiano V. Bizarro & Alan Saghatelian, 2024. "Rp3: Ribosome profiling-assisted proteogenomics improves coverage and confidence during microprotein discovery," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Heta Desai & Katrina H. Andrews & Kristina V. Bergersen & Samuel Ofori & Fengchao Yu & Flowreen Shikwana & Mark A. Arbing & Lisa M. Boatner & Miranda Villanueva & Nicholas Ung & Elaine F. Reed & Alexe, 2024. "Chemoproteogenomic stratification of the missense variant cysteinome," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    3. Ioanna Tzani & Marina Castro-Rivadeneyra & Paul Kelly & Lisa Strasser & Lin Zhang & Martin Clynes & Barry L. Karger & Niall Barron & Jonathan Bones & Colin Clarke, 2024. "Detection of host cell microprotein impurities in antibody drug products," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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