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classifieR a flexible interactive cloud-application for functional annotation of cancer transcriptomes
BACKGROUND: Transcriptionally informed predictions are increasingly important for sub-typing cancer patients, understanding underlying biology and to inform novel treatment strategies. For instance, colorectal cancers (CRCs) can be classified into four CRC consensus molecular subgroups (CMS) or five...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8974006/ https://www.ncbi.nlm.nih.gov/pubmed/35361119 http://dx.doi.org/10.1186/s12859-022-04641-x |
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author | Quinn, Gerard P. Sessler, Tamas Ahmaderaghi, Baharak Lambe, Shauna VanSteenhouse, Harper Lawler, Mark Wappett, Mark Seligmann, Bruce Longley, Daniel B. McDade, Simon S. |
author_facet | Quinn, Gerard P. Sessler, Tamas Ahmaderaghi, Baharak Lambe, Shauna VanSteenhouse, Harper Lawler, Mark Wappett, Mark Seligmann, Bruce Longley, Daniel B. McDade, Simon S. |
author_sort | Quinn, Gerard P. |
collection | PubMed |
description | BACKGROUND: Transcriptionally informed predictions are increasingly important for sub-typing cancer patients, understanding underlying biology and to inform novel treatment strategies. For instance, colorectal cancers (CRCs) can be classified into four CRC consensus molecular subgroups (CMS) or five intrinsic (CRIS) sub-types that have prognostic and predictive value. Breast cancer (BRCA) has five PAM50 molecular subgroups with similar value, and the OncotypeDX test provides transcriptomic based clinically actionable treatment-risk stratification. However, assigning samples to these subtypes and other transcriptionally inferred predictions is time consuming and requires significant bioinformatics experience. There is no "universal" method of using data from diverse assay/sequencing platforms to provide subgroup classification using the established classifier sets of genes (CMS, CRIS, PAM50, OncotypeDX), nor one which in provides additional useful functional annotations such as cellular composition, single-sample Gene Set Enrichment Analysis, or prediction of transcription factor activity. RESULTS: To address this bottleneck, we developed classifieR, an easy-to-use R-Shiny based web application that supports flexible rapid single sample annotation of transcriptional profiles derived from cancer patient samples form diverse platforms. We demonstrate the utility of the " classifieR" framework to applications focused on the analysis of transcriptional profiles from colorectal (classifieRc) and breast (classifieRb). Samples are annotated with disease relevant transcriptional subgroups (CMS/CRIS sub-types in classifieRc and PAM50/inferred OncotypeDX in classifieRb), estimation of cellular composition using MCP-counter and xCell, single-sample Gene Set Enrichment Analysis (ssGSEA) and transcription factor activity predictions with Discriminant Regulon Expression Analysis (DoRothEA). CONCLUSIONS: classifieR provides a framework which enables labs without access to a dedicated bioinformation can get information on the molecular makeup of their samples, providing an insight into patient prognosis, druggability and also as a tool for analysis and discovery. Applications are hosted online at https://generatr.qub.ac.uk/app/classifieRc and https://generatr.qub.ac.uk/app/classifieRb after signing up for an account on https://generatr.qub.ac.uk. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12859-022-04641-x. |
format | Online Article Text |
id | pubmed-8974006 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-89740062022-04-02 classifieR a flexible interactive cloud-application for functional annotation of cancer transcriptomes Quinn, Gerard P. Sessler, Tamas Ahmaderaghi, Baharak Lambe, Shauna VanSteenhouse, Harper Lawler, Mark Wappett, Mark Seligmann, Bruce Longley, Daniel B. McDade, Simon S. BMC Bioinformatics Software BACKGROUND: Transcriptionally informed predictions are increasingly important for sub-typing cancer patients, understanding underlying biology and to inform novel treatment strategies. For instance, colorectal cancers (CRCs) can be classified into four CRC consensus molecular subgroups (CMS) or five intrinsic (CRIS) sub-types that have prognostic and predictive value. Breast cancer (BRCA) has five PAM50 molecular subgroups with similar value, and the OncotypeDX test provides transcriptomic based clinically actionable treatment-risk stratification. However, assigning samples to these subtypes and other transcriptionally inferred predictions is time consuming and requires significant bioinformatics experience. There is no "universal" method of using data from diverse assay/sequencing platforms to provide subgroup classification using the established classifier sets of genes (CMS, CRIS, PAM50, OncotypeDX), nor one which in provides additional useful functional annotations such as cellular composition, single-sample Gene Set Enrichment Analysis, or prediction of transcription factor activity. RESULTS: To address this bottleneck, we developed classifieR, an easy-to-use R-Shiny based web application that supports flexible rapid single sample annotation of transcriptional profiles derived from cancer patient samples form diverse platforms. We demonstrate the utility of the " classifieR" framework to applications focused on the analysis of transcriptional profiles from colorectal (classifieRc) and breast (classifieRb). Samples are annotated with disease relevant transcriptional subgroups (CMS/CRIS sub-types in classifieRc and PAM50/inferred OncotypeDX in classifieRb), estimation of cellular composition using MCP-counter and xCell, single-sample Gene Set Enrichment Analysis (ssGSEA) and transcription factor activity predictions with Discriminant Regulon Expression Analysis (DoRothEA). CONCLUSIONS: classifieR provides a framework which enables labs without access to a dedicated bioinformation can get information on the molecular makeup of their samples, providing an insight into patient prognosis, druggability and also as a tool for analysis and discovery. Applications are hosted online at https://generatr.qub.ac.uk/app/classifieRc and https://generatr.qub.ac.uk/app/classifieRb after signing up for an account on https://generatr.qub.ac.uk. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12859-022-04641-x. BioMed Central 2022-03-31 /pmc/articles/PMC8974006/ /pubmed/35361119 http://dx.doi.org/10.1186/s12859-022-04641-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://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 Quinn, Gerard P. Sessler, Tamas Ahmaderaghi, Baharak Lambe, Shauna VanSteenhouse, Harper Lawler, Mark Wappett, Mark Seligmann, Bruce Longley, Daniel B. McDade, Simon S. classifieR a flexible interactive cloud-application for functional annotation of cancer transcriptomes |
title | classifieR a flexible interactive cloud-application for functional annotation of cancer transcriptomes |
title_full | classifieR a flexible interactive cloud-application for functional annotation of cancer transcriptomes |
title_fullStr | classifieR a flexible interactive cloud-application for functional annotation of cancer transcriptomes |
title_full_unstemmed | classifieR a flexible interactive cloud-application for functional annotation of cancer transcriptomes |
title_short | classifieR a flexible interactive cloud-application for functional annotation of cancer transcriptomes |
title_sort | classifier a flexible interactive cloud-application for functional annotation of cancer transcriptomes |
topic | Software |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8974006/ https://www.ncbi.nlm.nih.gov/pubmed/35361119 http://dx.doi.org/10.1186/s12859-022-04641-x |
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