TF-Prioritizer: a Java pipeline to prioritize condition-specific transcription factors

Background: Eukaryotic gene expression is controlled by cis-regulatory elements (CREs), including promoters and enhancers, which are bound by transcription factors (TFs). Differential expression of TFs and their binding affinity at putative CREs determine tissue- and developmental-specific transcrip...

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المؤلفون الرئيسيون: Hoffmann, M, Trummer, N, Schwartz, L, Jankowski, J, Lee, HK, Willruth, L, Lazareva, O, Yuan, K, Baumgarten, N, Schmidt, F, Baumbach, J, Schulz, MH, Blumenthal, DB, Hennighausen, L, List, M
التنسيق: Journal article
اللغة:English
منشور في: Oxford University Press 2023
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author Hoffmann, M
Trummer, N
Schwartz, L
Jankowski, J
Lee, HK
Willruth, L
Lazareva, O
Yuan, K
Baumgarten, N
Schmidt, F
Baumbach, J
Schulz, MH
Blumenthal, DB
Hennighausen, L
List, M
author_facet Hoffmann, M
Trummer, N
Schwartz, L
Jankowski, J
Lee, HK
Willruth, L
Lazareva, O
Yuan, K
Baumgarten, N
Schmidt, F
Baumbach, J
Schulz, MH
Blumenthal, DB
Hennighausen, L
List, M
author_sort Hoffmann, M
collection OXFORD
description Background: Eukaryotic gene expression is controlled by cis-regulatory elements (CREs), including promoters and enhancers, which are bound by transcription factors (TFs). Differential expression of TFs and their binding affinity at putative CREs determine tissue- and developmental-specific transcriptional activity. Consolidating genomic datasets can offer further insights into the accessibility of CREs, TF activity, and, thus, gene regulation. However, the integration and analysis of multimodal datasets are hampered by considerable technical challenges. While methods for highlighting differential TF activity from combined chromatin state data (e.g., chromatin immunoprecipitation [ChIP], ATAC, or DNase sequencing) and RNA sequencing data exist, they do not offer convenient usability, have limited support for large-scale data processing, and provide only minimal functionality for visually interpreting results. Results: We developed TF-Prioritizer, an automated pipeline that prioritizes condition-specific TFs from multimodal data and generates an interactive web report. We demonstrated its potential by identifying known TFs along with their target genes, as well as previously unreported TFs active in lactating mouse mammary glands. Additionally, we studied a variety of ENCODE datasets for cell lines K562 and MCF-7, including 12 histone modification ChIP sequencing as well as ATAC and DNase sequencing datasets, where we observe and discuss assay-specific differences. Conclusion: TF-Prioritizer accepts ATAC, DNase, or ChIP sequencing and RNA sequencing data as input and identifies TFs with differential activity, thus offering an understanding of genome-wide gene regulation, potential pathogenesis, and therapeutic targets in biomedical research.
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spelling oxford-uuid:4e9e51c9-87fc-457e-9638-9ab890c660fa2024-11-17T20:10:15ZTF-Prioritizer: a Java pipeline to prioritize condition-specific transcription factorsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4e9e51c9-87fc-457e-9638-9ab890c660faEnglishJisc Publications RouterOxford University Press2023Hoffmann, MTrummer, NSchwartz, LJankowski, JLee, HKWillruth, LLazareva, OYuan, KBaumgarten, NSchmidt, FBaumbach, JSchulz, MHBlumenthal, DBHennighausen, LList, MBackground: Eukaryotic gene expression is controlled by cis-regulatory elements (CREs), including promoters and enhancers, which are bound by transcription factors (TFs). Differential expression of TFs and their binding affinity at putative CREs determine tissue- and developmental-specific transcriptional activity. Consolidating genomic datasets can offer further insights into the accessibility of CREs, TF activity, and, thus, gene regulation. However, the integration and analysis of multimodal datasets are hampered by considerable technical challenges. While methods for highlighting differential TF activity from combined chromatin state data (e.g., chromatin immunoprecipitation [ChIP], ATAC, or DNase sequencing) and RNA sequencing data exist, they do not offer convenient usability, have limited support for large-scale data processing, and provide only minimal functionality for visually interpreting results. Results: We developed TF-Prioritizer, an automated pipeline that prioritizes condition-specific TFs from multimodal data and generates an interactive web report. We demonstrated its potential by identifying known TFs along with their target genes, as well as previously unreported TFs active in lactating mouse mammary glands. Additionally, we studied a variety of ENCODE datasets for cell lines K562 and MCF-7, including 12 histone modification ChIP sequencing as well as ATAC and DNase sequencing datasets, where we observe and discuss assay-specific differences. Conclusion: TF-Prioritizer accepts ATAC, DNase, or ChIP sequencing and RNA sequencing data as input and identifies TFs with differential activity, thus offering an understanding of genome-wide gene regulation, potential pathogenesis, and therapeutic targets in biomedical research.
spellingShingle Hoffmann, M
Trummer, N
Schwartz, L
Jankowski, J
Lee, HK
Willruth, L
Lazareva, O
Yuan, K
Baumgarten, N
Schmidt, F
Baumbach, J
Schulz, MH
Blumenthal, DB
Hennighausen, L
List, M
TF-Prioritizer: a Java pipeline to prioritize condition-specific transcription factors
title TF-Prioritizer: a Java pipeline to prioritize condition-specific transcription factors
title_full TF-Prioritizer: a Java pipeline to prioritize condition-specific transcription factors
title_fullStr TF-Prioritizer: a Java pipeline to prioritize condition-specific transcription factors
title_full_unstemmed TF-Prioritizer: a Java pipeline to prioritize condition-specific transcription factors
title_short TF-Prioritizer: a Java pipeline to prioritize condition-specific transcription factors
title_sort tf prioritizer a java pipeline to prioritize condition specific transcription factors
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