eRNAbase: a comprehensive database for decoding the regulatory eRNAs in human and mouse

Abstract

Enhancer RNAs (eRNAs) transcribed from distal active enhancers serve as key regulators in gene transcriptional regulation. The accumulation of eRNAs from multiple sequencing assays has led to an urgent need to comprehensively collect and process these data to illustrate the regulatory landscape of eRNAs. To address this need, we developed the eRNAbase (http://bio.liclab.net/eRNAbase/index.php) to store the massive available resources of human and mouse eRNAs and provide comprehensive annotation and analyses for eRNAs. The current version of eRNAbase cataloged 10 399 928 eRNAs from 1012 samples, including 858 human samples and 154 mouse samples. These eRNAs were first identified and uniformly processed from 14 eRNA-related experiment types manually collected from GEO/SRA and ENCODE. Importantly, the eRNAbase provides detailed and abundant (epi)genetic annotations in eRNA regions, such as super enhancers, enhancers, common single nucleotide polymorphisms, expression quantitative trait loci, transcription factor binding sites, CRISPR/Cas9 target sites, DNase I hypersensitivity sites, chromatin accessibility regions, methylation sites, chromatin interactions regions, topologically associating domains and RNA spatial interactions. Furthermore, the eRNAbase provides users with three novel analyses including eRNA-mediated pathway regulatory analysis, eRNA-based variation interpretation analysis and eRNA-mediated TF-target gene analysis. Hence, eRNAbase is a powerful platform to query, browse and visualize regulatory cues associated with eRNAs.

Graphical Abstract

Figure 1.

Data collection and construction of eRNAbase. eRNAs of eRNAbase were identified from 14 experiment types manually collected from GEO/SRA and ENCODE. Abundant (epi) genetic annotations, such as super enhancers, enhancers, open chromatins, common SNPs, eQTLs, risk SNPs, TFBS, CRISPR target sites, methylation sites, chromatin interactions regions and TADs. Moreover, eRNAbase contains analysis tools and functions to analyze, query, browse and visualize information associated with eRNAs.

Figure 2.

Main interfaces and usage of eRNAbase. (A) The navigation bar of eRNAbase. (B) Data browse page of eRNAbase. (C) Users can search eRNAs of interest via four queries. (D) Sample interface of eRNA sets from human K562 cell line, including sample overview, eRNA detail, genome proportion plot, peak distribution plot and chromosome distribution plot. (E) Detailed annotation information of eRNAs of interest, including eRNA overview information, annotation statistic, eRNA-mediated network, (epi)genetic annotation interactive table, eRNA associated genes, target gene expression, eRNA expression and TF binding information. (F) The eRNAbase provides three online analysis tools to help dissect eRNA-related regulation. (G) Genome browser interface. (H) Download interface.

Figure 3.

Case study panels of eRNAbase. (A) The navigation bar of eRNAbase. (B) Case study of CCAT1 query in target gene search. CCAT1 is a well-investigated eRNAs that plays key roles in cancers, especially in colon cancer. (C) Interactive result table of CCAT1 search, including the sample ID, eRNA ID, regions, genes and sample metadata information. (D-E) eRNA detailed information of the selected eRNA ‘Sample-01–013520459″, including eRNA overview, eRNA-mediated network, (epi)genetic annotation interactive table (TFBS, Super enhancer and Chromatin interaction), eRNA associated genes and eRNA expression. (F) Case study of NPPA super enhancer query in genomic region search. (G) Interactive result table of genomic region search. (H–I) eRNA detailed annotation information of the selected eRNA ‘Sample-01–02490014’.