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Pan-cancer transcriptomic analysis dissects immune and proliferative functions of APOBEC3 cytidine deaminases

APOBEC3 cytidine deaminases are largely known for their innate immune protection from viral infections. Recently, members of the family have been associated with a distinct mutational activity in some cancer types. We report a pan-tissue, pan-cancer analysis of RNA-seq data specific to the APOBEC3 g...

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Autores principales: Ng, Joseph C F, Quist, Jelmar, Grigoriadis, Anita, Malim, Michael H, Fraternali, Franca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379723/
https://www.ncbi.nlm.nih.gov/pubmed/30624727
http://dx.doi.org/10.1093/nar/gky1316
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author Ng, Joseph C F
Quist, Jelmar
Grigoriadis, Anita
Malim, Michael H
Fraternali, Franca
author_facet Ng, Joseph C F
Quist, Jelmar
Grigoriadis, Anita
Malim, Michael H
Fraternali, Franca
author_sort Ng, Joseph C F
collection PubMed
description APOBEC3 cytidine deaminases are largely known for their innate immune protection from viral infections. Recently, members of the family have been associated with a distinct mutational activity in some cancer types. We report a pan-tissue, pan-cancer analysis of RNA-seq data specific to the APOBEC3 genes in 8,951 tumours, 786 cancer cell lines and 6,119 normal tissues. By deconvolution of levels of different cell types in tumour admixtures, we demonstrate that APOBEC3B (A3B), the primary candidate as a cancer mutagen, shows little association with immune cell types compared to its paralogues. We present a pipeline called RESPECTEx (REconstituting SPecific Cell-Type Expression) and use it to deconvolute cell-type specific expression levels in a given cohort of tumour samples. We functionally annotate APOBEC3 co-expressing genes, and create an interactive visualization tool which ‘barcodes’ the functional enrichment (http://fraternalilab.kcl.ac.uk/apobec-barcodes/). These analyses reveal that A3B expression correlates with cell cycle and DNA repair genes, whereas the other APOBEC3 members display specificity for immune processes and immune cell populations. We offer molecular insights into the functions of individual APOBEC3 proteins in antiviral and proliferative contexts, and demonstrate the diversification this family of enzymes displays at the transcriptomic level, despite their high similarity in protein sequences and structures.
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spelling pubmed-63797232019-02-22 Pan-cancer transcriptomic analysis dissects immune and proliferative functions of APOBEC3 cytidine deaminases Ng, Joseph C F Quist, Jelmar Grigoriadis, Anita Malim, Michael H Fraternali, Franca Nucleic Acids Res Data Resources and Analyses APOBEC3 cytidine deaminases are largely known for their innate immune protection from viral infections. Recently, members of the family have been associated with a distinct mutational activity in some cancer types. We report a pan-tissue, pan-cancer analysis of RNA-seq data specific to the APOBEC3 genes in 8,951 tumours, 786 cancer cell lines and 6,119 normal tissues. By deconvolution of levels of different cell types in tumour admixtures, we demonstrate that APOBEC3B (A3B), the primary candidate as a cancer mutagen, shows little association with immune cell types compared to its paralogues. We present a pipeline called RESPECTEx (REconstituting SPecific Cell-Type Expression) and use it to deconvolute cell-type specific expression levels in a given cohort of tumour samples. We functionally annotate APOBEC3 co-expressing genes, and create an interactive visualization tool which ‘barcodes’ the functional enrichment (http://fraternalilab.kcl.ac.uk/apobec-barcodes/). These analyses reveal that A3B expression correlates with cell cycle and DNA repair genes, whereas the other APOBEC3 members display specificity for immune processes and immune cell populations. We offer molecular insights into the functions of individual APOBEC3 proteins in antiviral and proliferative contexts, and demonstrate the diversification this family of enzymes displays at the transcriptomic level, despite their high similarity in protein sequences and structures. Oxford University Press 2019-02-20 2019-01-09 /pmc/articles/PMC6379723/ /pubmed/30624727 http://dx.doi.org/10.1093/nar/gky1316 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Data Resources and Analyses
Ng, Joseph C F
Quist, Jelmar
Grigoriadis, Anita
Malim, Michael H
Fraternali, Franca
Pan-cancer transcriptomic analysis dissects immune and proliferative functions of APOBEC3 cytidine deaminases
title Pan-cancer transcriptomic analysis dissects immune and proliferative functions of APOBEC3 cytidine deaminases
title_full Pan-cancer transcriptomic analysis dissects immune and proliferative functions of APOBEC3 cytidine deaminases
title_fullStr Pan-cancer transcriptomic analysis dissects immune and proliferative functions of APOBEC3 cytidine deaminases
title_full_unstemmed Pan-cancer transcriptomic analysis dissects immune and proliferative functions of APOBEC3 cytidine deaminases
title_short Pan-cancer transcriptomic analysis dissects immune and proliferative functions of APOBEC3 cytidine deaminases
title_sort pan-cancer transcriptomic analysis dissects immune and proliferative functions of apobec3 cytidine deaminases
topic Data Resources and Analyses
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379723/
https://www.ncbi.nlm.nih.gov/pubmed/30624727
http://dx.doi.org/10.1093/nar/gky1316
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