Understanding transcriptional regulation by integrative analysis of transcription factor binding data
Chao Cheng,Roger P. Alexander,Rengqiang Min,Jing Leng,Kevin Y. Yip,Kevin Y. Yip,Joel Rozowsky,Koon-Kiu Yan,Xianjun Dong,Sarah Djebali,Yijun Ruan,Carrie A. Davis,Piero Carninci,Timo Lassman,Thomas R. Gingeras,Roderic Guigó,Ewan Birney,Zhiping Weng,Michael Snyder,Mark Gerstein +19 more
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TLDR
A notable difference is revealed in the prediction accuracy of expression levels of transcription start sites (TSSs) captured by different technologies and RNA extraction protocols, which implies that these features regulate transcription in a highly coordinated manner.Abstract:
Statistical models have been used to quantify the relationship between gene expression and transcription factor (TF) binding signals. Here we apply the models to the large-scale data generated by the ENCODE project to study transcriptional regulation by TFs. Our results reveal a notable difference in the prediction accuracy of expression levels of transcription start sites (TSSs) captured by different technologies and RNA extraction protocols. In general, the expression levels of TSSs with high CpG content are more predictable than those with low CpG content. For genes with alternative TSSs, the expression levels of downstream TSSs are more predictable than those of the upstream ones. Different TF categories and specific TFs vary substantially in their contributions to predicting expression. Between two cell lines, the differential expression of TSS can be precisely reflected by the difference of TF-binding signals in a quantitative manner, arguing against the conventional on-and-off model of TF binding. Finally, we explore the relationships between TF-binding signals and other chromatin features such as histone modifications and DNase hypersensitivity for determining expression. The models imply that these features regulate transcription in a highly coordinated manner.read more
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An integrated encyclopedia of DNA elements in the human genome
TL;DR: The Encyclopedia of DNA Elements project provides new insights into the organization and regulation of the authors' genes and genome, and is an expansive resource of functional annotations for biomedical research.
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An integrated encyclopedia of DNA elements in the human genome.
TL;DR: The Encyclopedia of DNA Elements project provides new insights into the organization and regulation of the authors' genes and genome, and is an expansive resource of functional annotations for biomedical research.
Journal ArticleDOI
Architecture of the human regulatory network derived from ENCODE data
Mark Gerstein,Anshul Kundaje,Manoj Hariharan,Stephen G. Landt,Koon-Kiu Yan,Chao Cheng,Xinmeng Jasmine Mu,Ekta Khurana,Joel Rozowsky,Roger P. Alexander,Renqiang Min,Renqiang Min,P. Alves,Alexej Abyzov,Nicholas Addleman,Nitin Bhardwaj,Alan P. Boyle,Philip Cayting,Alexandra Charos,David Z. Chen,Yong Cheng,Declan Clarke,Catharine L. Eastman,Ghia Euskirchen,Seth Frietze,Yao Fu,Jason Gertz,Fabian Grubert,Arif Harmanci,Preti Jain,Maya Kasowski,Phil Lacroute,Jing Jane Leng,Jin Lian,Hannah Monahan,Henriette O'Geen,Zhengqing Ouyang,E. Christopher Partridge,Dorrelyn Patacsil,Florencia Pauli,Debasish Raha,Lucía Ramírez,Timothy E. Reddy,Brian Reed,Minyi Shi,Teri Slifer,Jing Wang,Linfeng Wu,Xinqiong Yang,Kevin Y. Yip,Kevin Y. Yip,Gili Zilberman-Schapira,Serafim Batzoglou,Arend Sidow,Peggy J. Farnham,Richard M. Myers,Sherman M. Weissman,Michael Snyder +57 more
TL;DR: The combinatorial, co-association of transcription factors is found to be highly context specific: distinct combinations of factors bind at specific genomic locations.
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Sequential regulatory activity prediction across chromosomes with convolutional neural networks
David R. Kelley,Yakir A. Reshef,Maxwell L. Bileschi,David Belanger,Cory Y. McLean,Jasper Snoek +5 more
TL;DR: It is shown that model predictions for the influence of genomic variants on gene expression align well to causal variants underlying eQTLs in human populations and can be useful for generating mechanistic hypotheses to enable fine mapping of disease loci.
Journal ArticleDOI
The functional consequences of variation in transcription factor binding.
TL;DR: It is found that functional TF binding is enriched in regulatory elements that harbor a large number of TF binding sites, at sites with predicted higher binding affinity, and at sites that are enriched in genomic regions annotated as “active enhancers.”
References
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Journal Article
R: A language and environment for statistical computing.
TL;DR: Copyright (©) 1999–2012 R Foundation for Statistical Computing; permission is granted to make and distribute verbatim copies of this manual provided the copyright notice and permission notice are preserved on all copies.
Journal ArticleDOI
Random Forests
TL;DR: Internal estimates monitor error, strength, and correlation and these are used to show the response to increasing the number of features used in the forest, and are also applicable to regression.
Journal ArticleDOI
Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.
TL;DR: Induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions is demonstrated and iPS cells, designated iPS, exhibit the morphology and growth properties of ES cells and express ES cell marker genes.
Journal ArticleDOI
An integrated encyclopedia of DNA elements in the human genome
TL;DR: The Encyclopedia of DNA Elements project provides new insights into the organization and regulation of the authors' genes and genome, and is an expansive resource of functional annotations for biomedical research.
Journal ArticleDOI
RNA-Seq: a revolutionary tool for transcriptomics
TL;DR: The RNA-Seq approach to transcriptome profiling that uses deep-sequencing technologies provides a far more precise measurement of levels of transcripts and their isoforms than other methods.
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