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ARTDeco: automatic readthrough transcription detection
BACKGROUND: Mounting evidence suggests several diseases and biological processes target transcription termination to misregulate gene expression. Disruption of transcription termination leads to readthrough transcription past the 3′ end of genes, which can result in novel transcripts, changes in epi...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249449/ https://www.ncbi.nlm.nih.gov/pubmed/32456667 http://dx.doi.org/10.1186/s12859-020-03551-0 |
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author | Roth, Samuel J. Heinz, Sven Benner, Christopher |
author_facet | Roth, Samuel J. Heinz, Sven Benner, Christopher |
author_sort | Roth, Samuel J. |
collection | PubMed |
description | BACKGROUND: Mounting evidence suggests several diseases and biological processes target transcription termination to misregulate gene expression. Disruption of transcription termination leads to readthrough transcription past the 3′ end of genes, which can result in novel transcripts, changes in epigenetic states and altered 3D genome structure. RESULTS: We developed Automatic Readthrough Transcription Detection (ARTDeco), a tool to detect and analyze multiple features of readthrough transcription from RNA-seq and other next-generation sequencing (NGS) assays that profile transcriptional activity. ARTDeco robustly quantifies the global severity of readthrough phenotypes, and reliably identifies individual genes that fail to terminate (readthrough genes), are aberrantly transcribed due to upstream termination failure (read-in genes), and novel transcripts created as a result of readthrough (downstream of gene or DoG transcripts). We used ARTDeco to characterize readthrough transcription observed during influenza A virus (IAV) infection, validating its specificity and sensitivity by comparing its performance in samples infected with a mutant virus that fails to block transcription termination. We verify ARTDeco’s ability to detect readthrough as well as identify read-in genes from different experimental assays across multiple experimental systems with known defects in transcriptional termination, and show how these results can be leveraged to improve the interpretation of gene expression and downstream analysis. Applying ARTDeco to a gene expression data set from IAV-infected monocytes from different donors, we find strong evidence that read-in gene-associated expression quantitative trait loci (eQTLs) likely regulate genes upstream of read-in genes. This indicates that taking readthrough transcription into account is important for the interpretation of eQTLs in systems where transcription termination is blocked. CONCLUSIONS: ARTDeco aids researchers investigating readthrough transcription in a variety of systems and contexts. |
format | Online Article Text |
id | pubmed-7249449 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-72494492020-06-04 ARTDeco: automatic readthrough transcription detection Roth, Samuel J. Heinz, Sven Benner, Christopher BMC Bioinformatics Software BACKGROUND: Mounting evidence suggests several diseases and biological processes target transcription termination to misregulate gene expression. Disruption of transcription termination leads to readthrough transcription past the 3′ end of genes, which can result in novel transcripts, changes in epigenetic states and altered 3D genome structure. RESULTS: We developed Automatic Readthrough Transcription Detection (ARTDeco), a tool to detect and analyze multiple features of readthrough transcription from RNA-seq and other next-generation sequencing (NGS) assays that profile transcriptional activity. ARTDeco robustly quantifies the global severity of readthrough phenotypes, and reliably identifies individual genes that fail to terminate (readthrough genes), are aberrantly transcribed due to upstream termination failure (read-in genes), and novel transcripts created as a result of readthrough (downstream of gene or DoG transcripts). We used ARTDeco to characterize readthrough transcription observed during influenza A virus (IAV) infection, validating its specificity and sensitivity by comparing its performance in samples infected with a mutant virus that fails to block transcription termination. We verify ARTDeco’s ability to detect readthrough as well as identify read-in genes from different experimental assays across multiple experimental systems with known defects in transcriptional termination, and show how these results can be leveraged to improve the interpretation of gene expression and downstream analysis. Applying ARTDeco to a gene expression data set from IAV-infected monocytes from different donors, we find strong evidence that read-in gene-associated expression quantitative trait loci (eQTLs) likely regulate genes upstream of read-in genes. This indicates that taking readthrough transcription into account is important for the interpretation of eQTLs in systems where transcription termination is blocked. CONCLUSIONS: ARTDeco aids researchers investigating readthrough transcription in a variety of systems and contexts. BioMed Central 2020-05-26 /pmc/articles/PMC7249449/ /pubmed/32456667 http://dx.doi.org/10.1186/s12859-020-03551-0 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Software Roth, Samuel J. Heinz, Sven Benner, Christopher ARTDeco: automatic readthrough transcription detection |
title | ARTDeco: automatic readthrough transcription detection |
title_full | ARTDeco: automatic readthrough transcription detection |
title_fullStr | ARTDeco: automatic readthrough transcription detection |
title_full_unstemmed | ARTDeco: automatic readthrough transcription detection |
title_short | ARTDeco: automatic readthrough transcription detection |
title_sort | artdeco: automatic readthrough transcription detection |
topic | Software |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249449/ https://www.ncbi.nlm.nih.gov/pubmed/32456667 http://dx.doi.org/10.1186/s12859-020-03551-0 |
work_keys_str_mv | AT rothsamuelj artdecoautomaticreadthroughtranscriptiondetection AT heinzsven artdecoautomaticreadthroughtranscriptiondetection AT bennerchristopher artdecoautomaticreadthroughtranscriptiondetection |