Thirty biologically interpretable clusters of transcription factors distinguish cancer type
Abstract Background Transcription factors are essential regulators of gene expression and play critical roles in development, differentiation, and in many cancers. To carry out their regulatory programs, they must cooperate in networks and bind simultaneously to sites in promoter or enhancer regions...
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doaj-7c0c7be301a246cc87a910fe3a7348012020-11-25T01:38:33ZengBMCBMC Genomics1471-21642018-10-0119111410.1186/s12864-018-5093-zThirty biologically interpretable clusters of transcription factors distinguish cancer typeZachary B. Abrams0Mark Zucker1Min Wang2Amir Asiaee Taheri3Lynne V. Abruzzo4Kevin R. Coombes5Department of Biomedical Informatics, The Ohio State UniversityDepartment of Biomedical Informatics, The Ohio State UniversityDepartment of Biomedical Informatics, The Ohio State UniversityDepartment of Biomedical Informatics, The Ohio State UniversityDepartment of Pathology, The Ohio State UniversityDepartment of Biomedical Informatics, The Ohio State UniversityAbstract Background Transcription factors are essential regulators of gene expression and play critical roles in development, differentiation, and in many cancers. To carry out their regulatory programs, they must cooperate in networks and bind simultaneously to sites in promoter or enhancer regions of genes. We hypothesize that the mRNA co-expression patterns of transcription factors can be used both to learn how they cooperate in networks and to distinguish between cancer types. Results We recently developed a new algorithm, Thresher, that combines principal component analysis, outlier filtering, and von Mises-Fisher mixture models to cluster genes (in this case, transcription factors) based on expression, determining the optimal number of clusters in the process. We applied Thresher to the RNA-Seq expression data of 486 transcription factors from more than 10,000 samples of 33 kinds of cancer studied in The Cancer Genome Atlas (TCGA). We found that 30 clusters of transcription factors from a 29-dimensional principal component space were able to distinguish between most cancer types, and could separate tumor samples from normal controls. Moreover, each cluster of transcription factors could be either (i) linked to a tissue-specific expression pattern or (ii) associated with a fundamental biological process such as cell cycle, angiogenesis, apoptosis, or cytoskeleton. Clusters of the second type were more likely also to be associated with embryonically lethal mouse phenotypes. Conclusions Using our approach, we have shown that the mRNA expression patterns of transcription factors contain most of the information needed to distinguish different cancer types. The Thresher method is capable of discovering biologically interpretable clusters of genes. It can potentially be applied to other gene sets, such as signaling pathways, to decompose them into simpler, yet biologically meaningful, components.http://link.springer.com/article/10.1186/s12864-018-5093-zTCGAPan-cancerClusteringThresherGene expression |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zachary B. Abrams Mark Zucker Min Wang Amir Asiaee Taheri Lynne V. Abruzzo Kevin R. Coombes |
spellingShingle |
Zachary B. Abrams Mark Zucker Min Wang Amir Asiaee Taheri Lynne V. Abruzzo Kevin R. Coombes Thirty biologically interpretable clusters of transcription factors distinguish cancer type BMC Genomics TCGA Pan-cancer Clustering Thresher Gene expression |
author_facet |
Zachary B. Abrams Mark Zucker Min Wang Amir Asiaee Taheri Lynne V. Abruzzo Kevin R. Coombes |
author_sort |
Zachary B. Abrams |
title |
Thirty biologically interpretable clusters of transcription factors distinguish cancer type |
title_short |
Thirty biologically interpretable clusters of transcription factors distinguish cancer type |
title_full |
Thirty biologically interpretable clusters of transcription factors distinguish cancer type |
title_fullStr |
Thirty biologically interpretable clusters of transcription factors distinguish cancer type |
title_full_unstemmed |
Thirty biologically interpretable clusters of transcription factors distinguish cancer type |
title_sort |
thirty biologically interpretable clusters of transcription factors distinguish cancer type |
publisher |
BMC |
series |
BMC Genomics |
issn |
1471-2164 |
publishDate |
2018-10-01 |
description |
Abstract Background Transcription factors are essential regulators of gene expression and play critical roles in development, differentiation, and in many cancers. To carry out their regulatory programs, they must cooperate in networks and bind simultaneously to sites in promoter or enhancer regions of genes. We hypothesize that the mRNA co-expression patterns of transcription factors can be used both to learn how they cooperate in networks and to distinguish between cancer types. Results We recently developed a new algorithm, Thresher, that combines principal component analysis, outlier filtering, and von Mises-Fisher mixture models to cluster genes (in this case, transcription factors) based on expression, determining the optimal number of clusters in the process. We applied Thresher to the RNA-Seq expression data of 486 transcription factors from more than 10,000 samples of 33 kinds of cancer studied in The Cancer Genome Atlas (TCGA). We found that 30 clusters of transcription factors from a 29-dimensional principal component space were able to distinguish between most cancer types, and could separate tumor samples from normal controls. Moreover, each cluster of transcription factors could be either (i) linked to a tissue-specific expression pattern or (ii) associated with a fundamental biological process such as cell cycle, angiogenesis, apoptosis, or cytoskeleton. Clusters of the second type were more likely also to be associated with embryonically lethal mouse phenotypes. Conclusions Using our approach, we have shown that the mRNA expression patterns of transcription factors contain most of the information needed to distinguish different cancer types. The Thresher method is capable of discovering biologically interpretable clusters of genes. It can potentially be applied to other gene sets, such as signaling pathways, to decompose them into simpler, yet biologically meaningful, components. |
topic |
TCGA Pan-cancer Clustering Thresher Gene expression |
url |
http://link.springer.com/article/10.1186/s12864-018-5093-z |
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