ChEA: transcription factor regulation inferred from integrating genome-wide ChIP-X experiments

Lachmann, Alexander; Xu, Huilei; Krishnan, Jayanth; Berger, Seth; Mazloom, Amin R.; Ma’ayan, Avi

doi:10.1093/bioinformatics/btq466

Cited by 913 publications

(907 citation statements)

References 25 publications

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“…MARINa Analysis. We created a compendium of TFs and their targets (TF regulons) by combining information from four databases: SuperPathway (43), Literome (44), Multinet (45), and ChEA (46). We ran MARINa master regulator analysis using the previously described TF compendium.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

A basal stem cell signature identifies aggressive prostate cancer phenotypes

Smith

Sokolov

Uzunangelov

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

178

172

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Evidence from numerous cancers suggests that increased aggressiveness is accompanied by up-regulation of signaling pathways and acquisition of properties common to stem cells. It is unclear if different subtypes of late-stage cancer vary in stemness properties and whether or not these subtypes are transcriptionally similar to normal tissue stem cells. We report a gene signature specific for human prostate basal cells that is differentially enriched in various phenotypes of late-stage metastatic prostate cancer. We FACSpurified and transcriptionally profiled basal and luminal epithelial populations from the benign and cancerous regions of primary human prostates. High-throughput RNA sequencing showed the basal population to be defined by genes associated with stem cell signaling programs and invasiveness. Application of a 91-gene basal signature to gene expression datasets from patients with organconfined or hormone-refractory metastatic prostate cancer revealed that metastatic small cell neuroendocrine carcinoma was molecularly more stem-like than either metastatic adenocarcinoma or organ-confined adenocarcinoma. Bioinformatic analysis of the basal cell and two human small cell gene signatures identified a set of E2F target genes common between prostate small cell neuroendocrine carcinoma and primary prostate basal cells. Taken together, our data suggest that aggressive prostate cancer shares a conserved transcriptional program with normal adult prostate basal stem cells.RNA-seq | prostate cancer | stem cell signature | basal cell | neuroendocrine prostate cancer

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Section: Methodsmentioning

confidence: 99%

“…We created a network of TFs and their targets by combining transcriptional and genomic data from multiple databases (43)(44)(45)(46). MARINa used this TF network to compute a score for each TF's relative activity between the CD49f Hi and CD49f Lo populations.…”

Section: Benign and Cancer Gene Expression Profiles From The Same Epimentioning

confidence: 99%

A basal stem cell signature identifies aggressive prostate cancer phenotypes

Smith

Sokolov

Uzunangelov

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

178

172

View full text Add to dashboard Cite

show abstract

“…Among these genes were BRPF1, which maintains the anterior-posterior axis of craniofacial bones in fish 36 ; DEGS1, a predicted target of RUNX2 37 , a known driver of craniofacial diversity in carnivorans 38 ; and LTBP1 and LRIG1, both of which are associated with snout length in mice 39,40 . After FDR correction, we identified 259 genes under positive selection in the thylacine and 185 in the branch leading to Caninae (Supplementary Tables 12 and 13), which were then intersected with the list of genes containing homoplasious amino acid substitutions.…”

Section: Nature Ecology and Evolutionmentioning

confidence: 99%

“…4; markers [30][31][32][33][34][35][36][37][38][39][40]; three additional diagnostic WSINE1/1a elements present in thylacine and dasyurids but absent in the numbat and outgroup marsupials (Supplementary Fig. 4; markers 26-28); and one marker present in thylacine and numbat but absent in other dasyuromorphs (Supplementary Fig.…”

Section: Nature Ecology and Evolutionmentioning

confidence: 99%

Genome of the Tasmanian tiger provides insights into the evolution and demography of an extinct marsupial carnivore

et al. 2017

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The Tasmanian tiger or thylacine (Thylacinus cynocephalus) was the largest carnivorous Australian marsupial to survive into the modern era. Despite last sharing a common ancestor with the eutherian canids ~160 million years ago, their phenotypic resemblance is considered the most striking example of convergent evolution in mammals. The last known thylacine died in captivity in 1936 and many aspects of the evolutionary history of this unique marsupial apex predator remain unknown. Here we have sequenced the genome of a preserved thylacine pouch young specimen to clarify the phylogenetic position of the thylacine within the carnivorous marsupials, reconstruct its historical demography and examine the genetic basis of its convergence with canids. Retroposon insertion patterns placed the thylacine as the basal lineage in Dasyuromorphia and suggest incomplete lineage sorting in early dasyuromorphs. Demographic analysis indicated a long-term decline in genetic diversity starting well before the arrival of humans in Australia. In spite of their extraordinary phenotypic convergence, comparative genomic analyses demonstrated that amino acid homoplasies between the thylacine and canids are largely consistent with neutral evolution. Furthermore, the genes and pathways targeted by positive selection differ markedly between these species. Together, these findings support models of adaptive convergence driven primarily by cis-regulatory evolution.

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“…Extensive studies have been done to pinpoint the genetic determinants of gene regulation, with both experimental 1 and computational 2,3 approaches. Interactive applications and web services have been developed to infer regulatory networks based on transcription factor binding sites enriched in the gene promoter regions, based on either experimental ChIP-Seq data 4,5 or computational predicted TFBSs. 6 At the epigenetic level, histone modifications and DNA methylation can affect the chromatin structure and thus activate or repress gene expression.…”

mentioning

confidence: 99%

EpiRegNet: Constructing epigenetic regulatory network from high throughput gene expression data for humans

Wang

Plewczynski

et al. 2011

Epigenetics

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ChEA: transcription factor regulation inferred from integrating genome-wide ChIP-X experiments

Abstract: The ChEA software and ChIP-X database is freely available online at: http://amp.pharm.mssm.edu/lib/chea.jsp.

Cited by 913 publications

References 25 publications

A basal stem cell signature identifies aggressive prostate cancer phenotypes

A basal stem cell signature identifies aggressive prostate cancer phenotypes

Genome of the Tasmanian tiger provides insights into the evolution and demography of an extinct marsupial carnivore

EpiRegNet: Constructing epigenetic regulatory network from high throughput gene expression data for humans

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