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dc.contributor.authorErady, Chaitanya
dc.contributor.authorBoxall, Adam
dc.contributor.authorPuntambekar, Shraddha
dc.contributor.authorSuhas Jagannathan, N.
dc.contributor.authorChauhan, Ruchi
dc.contributor.authorChong, David
dc.contributor.authorMeena, Narendra
dc.contributor.authorKulkarni, Apurv
dc.contributor.authorKasabe, Bhagyashri
dc.contributor.authorPrathivadi Bhayankaram, Kethaki
dc.contributor.authorUmrania, Yagnesh
dc.contributor.authorAndreani, Adam
dc.contributor.authorNel, Jean
dc.contributor.authorWayland, Matthew T.
dc.contributor.authorPina, Cristina
dc.contributor.authorLilley, Kathryn S.
dc.contributor.authorPrabakaran, Sudhakaran
dc.date.accessioned2021-01-25T22:07:17Z
dc.date.available2021-01-25T22:07:17Z
dc.date.issued2021-01-25
dc.date.submitted2020-07-06
dc.identifier.others41525-020-00167-4
dc.identifier.other167
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/316654
dc.description.abstractAbstract: Uncharacterized and unannotated open-reading frames, which we refer to as novel open reading frames (nORFs), may sometimes encode peptides that remain unexplored for novel therapeutic opportunities. To our knowledge, no systematic identification and characterization of transcripts encoding nORFs or their translation products in cancer, or in any other physiological process has been performed. We use our curated nORFs database (nORFs.org), together with RNA-Seq data from The Cancer Genome Atlas (TCGA) and Genotype-Expression (GTEx) consortiums, to identify transcripts containing nORFs that are expressed frequently in cancer or matched normal tissue across 22 cancer types. We show nORFs are subject to extensive dysregulation at the transcript level in cancer tissue and that a small subset of nORFs are associated with overall patient survival, suggesting that nORFs may have prognostic value. We also show that nORF products can form protein-like structures with post-translational modifications. Finally, we perform in silico screening for inhibitors against nORF-encoded proteins that are disrupted in stomach and esophageal cancer, showing that they can potentially be targeted by inhibitors. We hope this work will guide and motivate future studies that perform in-depth characterization of nORF functions in cancer and other diseases.
dc.languageen
dc.publisherNature Publishing Group UK
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectArticle
dc.subject/631/553
dc.subject/631/208
dc.subjectarticle
dc.titlePan-cancer analysis of transcripts encoding novel open-reading frames (nORFs) and their potential biological functions
dc.typeArticle
dc.date.updated2021-01-25T22:07:17Z
prism.issueIdentifier1
prism.publicationNamenpj Genomic Medicine
prism.volume6
dc.identifier.doi10.17863/CAM.63767
dcterms.dateAccepted2020-11-18
rioxxterms.versionofrecord10.1038/s41525-020-00167-4
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidBoxall, Adam [0000-0002-3677-3043]
dc.contributor.orcidSuhas Jagannathan, N. [0000-0002-1857-8789]
dc.contributor.orcidWayland, Matthew T. [0000-0002-8095-858X]
dc.contributor.orcidLilley, Kathryn S. [0000-0003-0594-6543]
dc.contributor.orcidPrabakaran, Sudhakaran [0000-0002-6527-1085]
dc.identifier.eissn2056-7944


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)