scholarly journals Modular Evolution of DNA-Binding Preference of a Tbrain Transcription Factor Provides a Mechanism for Modifying Gene Regulatory Networks

2014 ◽  
Vol 31 (10) ◽  
pp. 2672-2688 ◽  
Author(s):  
Alys M. Cheatle Jarvela ◽  
Lisa Brubaker ◽  
Anastasia Vedenko ◽  
Anisha Gupta ◽  
Bruce A. Armitage ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Modular Evolution ◽  
Binding Preference ◽  
Gene Regulatory

scholarly journals Modeling transcriptional regulation using gene regulatory networks based on multi-omics data sources

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Neel Patel ◽  
William S. Bush
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Prediction Models ◽  
Long Distance ◽  
Chromatin Looping ◽  
Gene Regulatory ◽  
The Impact

Abstract Background Transcriptional regulation is complex, requiring multiple cis (local) and trans acting mechanisms working in concert to drive gene expression, with disruption of these processes linked to multiple diseases. Previous computational attempts to understand the influence of regulatory mechanisms on gene expression have used prediction models containing input features derived from cis regulatory factors. However, local chromatin looping and trans-acting mechanisms are known to also influence transcriptional regulation, and their inclusion may improve model accuracy and interpretation. In this study, we create a general model of transcription factor influence on gene expression by incorporating both cis and trans gene regulatory features. Results We describe a computational framework to model gene expression for GM12878 and K562 cell lines. This framework weights the impact of transcription factor-based regulatory data using multi-omics gene regulatory networks to account for both cis and trans acting mechanisms, and measures of the local chromatin context. These prediction models perform significantly better compared to models containing cis-regulatory features alone. Models that additionally integrate long distance chromatin interactions (or chromatin looping) between distal transcription factor binding regions and gene promoters also show improved accuracy. As a demonstration of their utility, effect estimates from these models were used to weight cis-regulatory rare variants for sequence kernel association test analyses of gene expression. Conclusions Our models generate refined effect estimates for the influence of individual transcription factors on gene expression, allowing characterization of their roles across the genome. This work also provides a framework for integrating multiple data types into a single model of transcriptional regulation.

scholarly journals Accurate differential analysis of transcription factor activity from gene expression

2018 ◽  
Author(s):  
Viren Amin ◽  
Murat Can Cobanoglu
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Expression Data ◽  
Differential Analysis ◽  
Gene Regulatory ◽  
Context Specific ◽  
Tf Gene ◽  
Perturbation Estimation

AbstractWe present EPEE (Effector and Perturbation Estimation Engine), a method for differential analysis of transcription factor (TF) activity from gene expression data. EPEE addresses two principal challenges in the field, namely incorporating context-specific TF-gene regulatory networks, and accounting for the fact that TF activity inference is intrinsically coupled for all TFs that share targets. Our validations in well-studied immune and cancer contexts show that addressing the overlap challenge and using state-of-the-art regulatory networks enable EPEE to consistently produce accurate results. (Accessible at: https://github.com/Cobanoglu-Lab/EPEE)

scholarly journals Gene regulatory networks and transcription factor transcriptomics

2009 ◽  
Vol 25 ◽  
pp. S318
Author(s):  
B. Mueller-Roeber ◽  
S. Arvidsson ◽  
S. Balazadeh ◽  
L.G.G. Corrêa ◽  
P. Pérez-Rodríguez ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Gene Regulatory

scholarly journals Modeling Transcriptional Regulation Using Gene Regulatory Networks Based on Multi-Omics Data Sources

2020 ◽  
Author(s):  
Neel Patel ◽  
William Bush
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Prediction Models ◽  
Long Distance ◽  
Chromatin Looping ◽  
Gene Regulatory ◽  
The Impact

Abstract BackgroundTranscriptional regulation is complex, requiring multiple cis(local) and trans acting mechanisms working in concert to drive gene expression, with disruption of these processes linked to multiple diseases. Previous computational attempts to understand the influence of regulatory mechanisms on gene expression have used prediction models containing input features derived from cis regulatory factors. However, local chromatin looping and trans-acting mechanisms are known to also influence transcriptional regulation, and their inclusion may improve model accuracy and interpretation. ResultsWe describe a computational framework to model gene expression for GM12878 and K562 cell lines. This framework weights the impact of transcription factor-based regulatory data using multi-omics gene regulatory networks to account for both cis and trans acting mechanisms, and the local chromatin context. These prediction models perform significantly better compared to models containing cis-regulatory features alone. Models that additionally integrate long distance chromatin interactions (or chromatin looping) between distal transcription factor binding regions and gene promoters also show improved accuracy. As a demonstration of their utility, effect estimates from these models were used to weight cis-regulatory rare variants for SKAT(sequence kernel association test) analyses of gene expression. ConclusionsOur models generate refined effect estimates for individual transcription factors, allow characterization of their roles across the genome, and provide a framework for integrating multiple data types into a single model of transcriptional regulation.

scholarly journals Constructing gene regulatory networks using epigenetic data

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Abhijeet Rajendra Sonawane ◽  
Dawn L. DeMeo ◽  
John Quackenbush ◽  
Kimberly Glass
Keyword(s):  
Transcription Factor ◽  
Gene Regulatory Networks ◽  
Regulatory Network ◽  
Message Passing ◽  
Regulatory Networks ◽  
Transcription Factor Binding ◽  
Network Reconstruction ◽  
Sequence Motif ◽  
Factor Binding ◽  
Gene Regulatory

AbstractThe biological processes that drive cellular function can be represented by a complex network of interactions between regulators (transcription factors) and their targets (genes). A cell’s epigenetic state plays an important role in mediating these interactions, primarily by influencing chromatin accessibility. However, how to effectively use epigenetic data when constructing a gene regulatory network remains an open question. Almost all existing network reconstruction approaches focus on estimating transcription factor to gene connections using transcriptomic data. In contrast, computational approaches for analyzing epigenetic data generally focus on improving transcription factor binding site predictions rather than deducing regulatory network relationships. We bridged this gap by developing SPIDER, a network reconstruction approach that incorporates epigenetic data into a message-passing framework to estimate gene regulatory networks. We validated SPIDER’s predictions using ChIP-seq data from ENCODE and found that SPIDER networks are both highly accurate and include cell-line-specific regulatory interactions. Notably, SPIDER can recover ChIP-seq verified transcription factor binding events in the regulatory regions of genes that do not have a corresponding sequence motif. The networks estimated by SPIDER have the potential to identify novel hypotheses that will allow us to better characterize cell-type and phenotype specific regulatory mechanisms.

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