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Fold-Change-Specific Enrichment Analysis (FSEA): Quantification of Transcriptional Response Magnitude for Functional Gene Groups

Gene expression profiling data contains more information than is routinely extracted with standard approaches. Here we present Fold-Change-Specific Enrichment Analysis (FSEA), a new method for functional annotation of differentially expressed genes from transcriptome data with respect to their fold...

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Autores principales: Wiebe, Daniil S., Omelyanchuk, Nadezhda A., Mukhin, Aleksei M., Grosse, Ivo, Lashin, Sergey A., Zemlyanskaya, Elena V., Mironova, Victoria V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230499/
https://www.ncbi.nlm.nih.gov/pubmed/32316383
http://dx.doi.org/10.3390/genes11040434
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author Wiebe, Daniil S.
Omelyanchuk, Nadezhda A.
Mukhin, Aleksei M.
Grosse, Ivo
Lashin, Sergey A.
Zemlyanskaya, Elena V.
Mironova, Victoria V.
author_facet Wiebe, Daniil S.
Omelyanchuk, Nadezhda A.
Mukhin, Aleksei M.
Grosse, Ivo
Lashin, Sergey A.
Zemlyanskaya, Elena V.
Mironova, Victoria V.
author_sort Wiebe, Daniil S.
collection PubMed
description Gene expression profiling data contains more information than is routinely extracted with standard approaches. Here we present Fold-Change-Specific Enrichment Analysis (FSEA), a new method for functional annotation of differentially expressed genes from transcriptome data with respect to their fold changes. FSEA identifies Gene Ontology (GO) terms, which are shared by the group of genes with a similar magnitude of response, and assesses these changes. GO terms found by FSEA are fold-change-specifically (e.g., weakly, moderately, or strongly) affected by a stimulus under investigation. We demonstrate that many responses to abiotic factors, mutations, treatments, and diseases occur in a fold-change-specific manner. FSEA analyses suggest that there are two prevailing responses of functionally-related gene groups, either weak or strong. Notably, some of the fold-change-specific GO terms are invisible by classical algorithms for functional gene enrichment, Singular Enrichment Analysis (SEA), and Gene Set Enrichment Analysis (GSEA). These are GO terms not enriched compared to the genome background but strictly regulated by a factor within specific fold-change intervals. FSEA analysis of a cancer-related transcriptome suggested that the gene groups with a tightly coordinated response can be the valuable source to search for possible regulators, markers, and therapeutic targets in oncogenic processes. Availability and Implementation: FSEA is implemented as the FoldGO Bioconductor R package and a web-server.
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spelling pubmed-72304992020-05-22 Fold-Change-Specific Enrichment Analysis (FSEA): Quantification of Transcriptional Response Magnitude for Functional Gene Groups Wiebe, Daniil S. Omelyanchuk, Nadezhda A. Mukhin, Aleksei M. Grosse, Ivo Lashin, Sergey A. Zemlyanskaya, Elena V. Mironova, Victoria V. Genes (Basel) Article Gene expression profiling data contains more information than is routinely extracted with standard approaches. Here we present Fold-Change-Specific Enrichment Analysis (FSEA), a new method for functional annotation of differentially expressed genes from transcriptome data with respect to their fold changes. FSEA identifies Gene Ontology (GO) terms, which are shared by the group of genes with a similar magnitude of response, and assesses these changes. GO terms found by FSEA are fold-change-specifically (e.g., weakly, moderately, or strongly) affected by a stimulus under investigation. We demonstrate that many responses to abiotic factors, mutations, treatments, and diseases occur in a fold-change-specific manner. FSEA analyses suggest that there are two prevailing responses of functionally-related gene groups, either weak or strong. Notably, some of the fold-change-specific GO terms are invisible by classical algorithms for functional gene enrichment, Singular Enrichment Analysis (SEA), and Gene Set Enrichment Analysis (GSEA). These are GO terms not enriched compared to the genome background but strictly regulated by a factor within specific fold-change intervals. FSEA analysis of a cancer-related transcriptome suggested that the gene groups with a tightly coordinated response can be the valuable source to search for possible regulators, markers, and therapeutic targets in oncogenic processes. Availability and Implementation: FSEA is implemented as the FoldGO Bioconductor R package and a web-server. MDPI 2020-04-17 /pmc/articles/PMC7230499/ /pubmed/32316383 http://dx.doi.org/10.3390/genes11040434 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wiebe, Daniil S.
Omelyanchuk, Nadezhda A.
Mukhin, Aleksei M.
Grosse, Ivo
Lashin, Sergey A.
Zemlyanskaya, Elena V.
Mironova, Victoria V.
Fold-Change-Specific Enrichment Analysis (FSEA): Quantification of Transcriptional Response Magnitude for Functional Gene Groups
title Fold-Change-Specific Enrichment Analysis (FSEA): Quantification of Transcriptional Response Magnitude for Functional Gene Groups
title_full Fold-Change-Specific Enrichment Analysis (FSEA): Quantification of Transcriptional Response Magnitude for Functional Gene Groups
title_fullStr Fold-Change-Specific Enrichment Analysis (FSEA): Quantification of Transcriptional Response Magnitude for Functional Gene Groups
title_full_unstemmed Fold-Change-Specific Enrichment Analysis (FSEA): Quantification of Transcriptional Response Magnitude for Functional Gene Groups
title_short Fold-Change-Specific Enrichment Analysis (FSEA): Quantification of Transcriptional Response Magnitude for Functional Gene Groups
title_sort fold-change-specific enrichment analysis (fsea): quantification of transcriptional response magnitude for functional gene groups
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230499/
https://www.ncbi.nlm.nih.gov/pubmed/32316383
http://dx.doi.org/10.3390/genes11040434
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