Description

This track represents the ReMap Atlas of regulatory regions, which consists of a large-scale integrative analysis of all Public ChIP-seq data for transcriptional regulators from GEO, ArrayExpress, and ENCODE.

Below is a schematic diagram of the types of regulatory regions:

• ReMap 2022 Atlas (all peaks for each analyzed data set)
• ReMap 2022 Non-redundant peaks (merged similar target)
• ReMap 2022 Cis Regulatory Modules

Display Conventions and Configuration

• Each transcription factor follows a specific RGB color.
• ChIP-seq peak summits are represented by vertical bars.
• Hsap: A data set is defined as a ChIP/Exo-seq experiment in a given GEO/ArrayExpress/ENCODE series (e.g. GSE41561), for a given TF (e.g. ESR1), in a particular biological condition (e.g. MCF-7).
  Data sets are labeled with the concatenation of these three pieces of information (e.g. GSE41561.ESR1.MCF-7).
• Atha: The data set is defined as a ChIP-seq experiment in a given series (e.g. GSE94486), for a given target (e.g. ARR1), in a particular biological condition (i.e. ecotype, tissue type, experimental conditions; e.g. Col-0_seedling_3d-6BA-4h).
  Data sets are labeled with the concatenation of these three pieces of information (e.g. GSE94486.ARR1.Col-0_seedling_3d-6BA-4h).

Methods

This 4th release of ReMap (2022) presents the analysis of a total of 8,103 quality controlled ChIP-seq (n=7,895) and ChIP-exo (n=208) data sets from public sources (GEO, ArrayExpress, ENCODE). The ChIP-seq/exo data sets have been mapped to the GRCh38/hg38 human assembly. The data set is defined as a ChIP-seq experiment in a given series (e.g. GSE46237), for a given TF (e.g. NR2C2), in a particular biological condition (i.e. cell line, tissue type, disease state, or experimental conditions; e.g. HELA). Data sets were labeled by concatenating these three pieces of information, such as GSE46237.NR2C2.HELA.

Those merged analyses cover a total of 1,211 DNA-binding proteins (transcriptional regulators) such as a variety of transcription factors (TFs), transcription co-activators (TCFs), and chromatin-remodeling factors (CRFs) for 182 million peaks.

GEO & ArrayExpress

Public ChIP-seq data sets were extracted from Gene Expression Omnibus (GEO) and ArrayExpress (AE) databases. For GEO, the query '('chip seq' OR 'chipseq' OR 'chip sequencing') AND 'Genome binding/occupancy profiling by high throughput sequencing' AND 'homo sapiens'[organism] AND NOT 'ENCODE'[project]' was used to return a list of all potential data sets to analyze, which were then manually assessed for further analyses. Data sets involving polymerases (i.e. Pol2 and Pol3), and some mutated or fused TFs (e.g. KAP1 N/C terminal mutation, GSE27929) were excluded.

ENCODE

Available ENCODE ChIP-seq data sets for transcriptional regulators from the ENCODE portal were processed with the standardized ReMap pipeline. The list of ENCODE data was retrieved as FASTQ files from the ENCODE portal using the following filters:

• Assay: "ChIP-seq"
• Organism: "Homo sapiens"
• Target of assay: "transcription factor"
• Available data: "fastq" on 2016 June 21st

ChIP-seq processing

Both Public and ENCODE data were processed similarly. Bowtie 2 (PMC3322381) (version 2.2.9) with options -end-to-end -sensitive was used to align all reads on the genome. Biological and technical replicates for each unique combination of GSE/TF/Cell type or Biological condition were used for peak calling. TFBS were identified using MACS2 peak-calling tool (PMC3120977) (version 2.1.1.2) in order to follow ENCODE ChIP-seq guidelines, with stringent thresholds (MACS2 default thresholds, p-value: 1e-5). An input data set was used when available.

Quality assessment

To assess the quality of public data sets, a score was computed based on the cross-correlation and the FRiP (fraction of reads in peaks) metrics developed by the ENCODE Consortium (https://genome.ucsc.edu/ENCODE/qualityMetrics.html). Two thresholds were defined for each of the two cross-correlation ratios (NSC, normalized strand coefficient: 1.05 and 1.10; RSC, relative strand coefficient: 0.8 and 1.0). Detailed descriptions of the ENCODE quality coefficients can be found at https://genome.ucsc.edu/ENCODE/qualityMetrics.html. The phantompeak tools suite was used (https://code.google.com/p/phantompeakqualtools/) to compute RSC and NSC.

Please refer to the ReMap 2022, 2020, and 2018 publications for more details (citation below).

Data Access

ReMap Atlas of regulatory regions data can be explored interactively with the Table Browser and cross-referenced with the Data Integrator. For programmatic access, the track can be accessed using the Genome Browser's REST API. ReMap annotations can be downloaded from the Genome Browser's download server as a bigBed file. This compressed binary format can be remotely queried through command line utilities. Please note that some of the download files can be quite large.

Individual BED files for specific TFs, cells/biotypes, or data sets can be found and downloaded on the ReMap website.

References

Chèneby J, Gheorghe M, Artufel M, Mathelier A, Ballester B. ReMap 2018: an updated atlas of regulatory regions from an integrative analysis of DNA-binding ChIP- seq experiments. Nucleic Acids Res. 2018 Jan 4;46(D1):D267-D275. PMID: 29126285; PMC: PMC5753247

Chèneby J, Ménétrier Z, Mestdagh M, Rosnet T, Douida A, Rhalloussi W, Bergon A, Lopez F, Ballester B. ReMap 2020: a database of regulatory regions from an integrative analysis of Human and Arabidopsis DNA-binding sequencing experiments. Nucleic Acids Res. 2020 Jan 8;48(D1):D180-D188. PMID: 31665499; PMC: PMC7145625

Griffon A, Barbier Q, Dalino J, van Helden J, Spicuglia S, Ballester B. Integrative analysis of public ChIP-seq experiments reveals a complex multi-cell regulatory landscape. Nucleic Acids Res. 2015 Feb 27;43(4):e27. PMID: 25477382; PMC: PMC4344487

Hammal F, de Langen P, Bergon A, Lopez F, Ballester B. ReMap 2022: a database of Human, Mouse, Drosophila and Arabidopsis regulatory regions from an integrative analysis of DNA-binding sequencing experiments. Nucleic Acids Res. 2022 Jan 7;50(D1):D316-D325. PMID: 34751401; PMC: PMC8728178