Abstract
i-cisTarget is a web tool to predict regulators of a set of genomic regions, such as ChIP-seq peaks or co-regulated/similar enhancers. i-cisTarget can also be used to identify upstream regulators and their target enhancers starting from a set of co-expressed genes. Whereas the original version of i-cisTarget was focused on Drosophila data, the 2015 update also provides support for human and mouse data. i-cisTarget detects transcription factor motifs (position weight matrices) and experimental data tracks (e.g. from ENCODE, Roadmap Epigenomics) that are enriched in the input set of regions. As experimental data tracks we include transcription factor ChIP-seq data, histone modification ChIP-seq data and open chromatin data. The underlying processing method is based on a ranking-and-recovery procedure, allowing accurate determination of enrichment across heterogeneous datasets, while also discriminating direct from indirect target regions through a ‘leading edge’ analysis. We illustrate i-cisTarget on various Ewing sarcoma datasets to identify EWS-FLI1 targets starting from ChIP-seq, differential ATAC-seq, differential H3K27ac and differential gene expression data. Use of i-cisTarget is free and open to all, and there is no login requirement. Address: http://gbiomed.kuleuven.be/apps/lcb/i-cisTarget.
Highlights
The field of regulatory genomics is generating vast amounts of sequencing data related to transcription factor binding, chromatin activity and gene expression
Whereas many tools are available for the functional analysis of gene signatures, such as Gene Ontology enrichment analysis [1,2,3] and for the identification of enriched transcription factor motifs in co-expressed gene sets [4,5,6,7,8], fewer web tools exist to analyse sets of genomic regions
To delineate human candidate regulatory regions (CRRs) the following publicly available regulatory data were used: DNAseI Hypersensitive (DHS) uniform clustered peaks across 125 cell lines from ENCODE [15], General Binding Preference models [16], regulatory elements from ORegAnno [17], VistaEnhancers [18], predicted cisregulatory modules [19], CpG islands and proximal promoters (both downloaded from UCSC table browser [20]), conserved non-coding sequences (CNS) and ultraconserved elements (UCR)
Summary
The field of regulatory genomics is generating vast amounts of sequencing data related to transcription factor binding, chromatin activity and gene expression. A third kind of analysis that is often performed on genomic regions is to associate each region to one or more candidate target genes and analyse the function (e.g. by GO [13]) of the resulting target gene set. Such a procedure is implemented by the web tool GREAT [14]. One of the challenges is to make these analyses computationally tractable, so that they can be run in a web tool To this end, we generated collections of candidate regulatory regions (CRRs) for the human and mouse genome. The output of icisTarget are predictions of key transcription factors alongside a prioritized list of direct transcriptional targets and the actual cis-regulatory modules (CRM) and transcription factor binding sites
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