Pan-cancer analysis of transcripts encoding novel open-reading frames (nORFs) and their potential biological functions

Abstract 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...

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Autores principales:	Chaitanya Erady, Adam Boxall, Shraddha Puntambekar, N. Suhas Jagannathan, Ruchi Chauhan, David Chong, Narendra Meena, Apurv Kulkarni, Bhagyashri Kasabe, Kethaki Prathivadi Bhayankaram, Yagnesh Umrania, Adam Andreani, Jean Nel, Matthew T. Wayland, Cristina Pina, Kathryn S. Lilley, Sudhakaran Prabakaran
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Genetics QH426-470
Acceso en línea:	https://doaj.org/article/410f193223914d33badf65ab4ce92412
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spelling	oai:doaj.org-article:410f193223914d33badf65ab4ce924122021-12-02T13:24:08ZPan-cancer analysis of transcripts encoding novel open-reading frames (nORFs) and their potential biological functions10.1038/s41525-020-00167-42056-7944https://doaj.org/article/410f193223914d33badf65ab4ce924122021-01-01T00:00:00Zhttps://doi.org/10.1038/s41525-020-00167-4https://doaj.org/toc/2056-7944Abstract 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.Chaitanya EradyAdam BoxallShraddha PuntambekarN. Suhas JagannathanRuchi ChauhanDavid ChongNarendra MeenaApurv KulkarniBhagyashri KasabeKethaki Prathivadi BhayankaramYagnesh UmraniaAdam AndreaniJean NelMatthew T. WaylandCristina PinaKathryn S. LilleySudhakaran PrabakaranNature PortfolioarticleMedicineRGeneticsQH426-470ENnpj Genomic Medicine, Vol 6, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Genetics QH426-470
spellingShingle	Medicine R Genetics QH426-470 Chaitanya Erady Adam Boxall Shraddha Puntambekar N. Suhas Jagannathan Ruchi Chauhan David Chong Narendra Meena Apurv Kulkarni Bhagyashri Kasabe Kethaki Prathivadi Bhayankaram Yagnesh Umrania Adam Andreani Jean Nel Matthew T. Wayland Cristina Pina Kathryn S. Lilley Sudhakaran Prabakaran Pan-cancer analysis of transcripts encoding novel open-reading frames (nORFs) and their potential biological functions
description	Abstract 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.
format	article
author	Chaitanya Erady Adam Boxall Shraddha Puntambekar N. Suhas Jagannathan Ruchi Chauhan David Chong Narendra Meena Apurv Kulkarni Bhagyashri Kasabe Kethaki Prathivadi Bhayankaram Yagnesh Umrania Adam Andreani Jean Nel Matthew T. Wayland Cristina Pina Kathryn S. Lilley Sudhakaran Prabakaran
author_facet	Chaitanya Erady Adam Boxall Shraddha Puntambekar N. Suhas Jagannathan Ruchi Chauhan David Chong Narendra Meena Apurv Kulkarni Bhagyashri Kasabe Kethaki Prathivadi Bhayankaram Yagnesh Umrania Adam Andreani Jean Nel Matthew T. Wayland Cristina Pina Kathryn S. Lilley Sudhakaran Prabakaran
author_sort	Chaitanya Erady
title	Pan-cancer analysis of transcripts encoding novel open-reading frames (nORFs) and their potential biological functions
title_short	Pan-cancer analysis of transcripts encoding novel open-reading frames (nORFs) and their potential biological functions
title_full	Pan-cancer analysis of transcripts encoding novel open-reading frames (nORFs) and their potential biological functions
title_fullStr	Pan-cancer analysis of transcripts encoding novel open-reading frames (nORFs) and their potential biological functions
title_full_unstemmed	Pan-cancer analysis of transcripts encoding novel open-reading frames (nORFs) and their potential biological functions
title_sort	pan-cancer analysis of transcripts encoding novel open-reading frames (norfs) and their potential biological functions
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/410f193223914d33badf65ab4ce92412
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Pan-cancer analysis of transcripts encoding novel open-reading frames (nORFs) and their potential biological functions

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