ReMap 2022: a database of Human, Mouse, Drosophila and Arabidopsis regulatory regions from an integrative analysis of DNA-binding sequencing experiments

Abstract

ReMap (https://remap.univ-amu.fr) aims to provide manually curated, high-quality catalogs of regulatory regions resulting from a large-scale integrative analysis of DNA-binding experiments in Human, Mouse, Fly and Arabidopsis thaliana for hundreds of transcription factors and regulators. In this 2022 update, we have uniformly processed >11 000 DNA-binding sequencing datasets from public sources across four species. The updated Human regulatory atlas includes 8103 datasets covering a total of 1210 transcriptional regulators (TRs) with a catalog of 182 million (M) peaks, while the updated Arabidopsis atlas reaches 4.8M peaks, 423 TRs across 694 datasets. Also, this ReMap release is enriched by two new regulatory catalogs for Mus musculus and Drosophila melanogaster. First, the Mouse regulatory catalog consists of 123M peaks across 648 TRs as a result of the integration and validation of 5503 ChIP-seq datasets. Second, the Drosophila melanogaster catalog contains 16.6M peaks across 550 TRs from the integration of 1205 datasets. The four regulatory catalogs are browsable through track hubs at UCSC, Ensembl and NCBI genome browsers. Finally, ReMap 2022 comes with a new Cis Regulatory Module identification method, improved quality controls, faster search results, and better user experience with an interactive tour and video tutorials on browsing and filtering ReMap catalogs.

JASPAR 2022: the 9th release of the open-access database of transcription factor binding profiles

“…In the 9th release of JASPAR, we discarded unused collections introduced in early releases of the database ( 27–29 ) that either did not correspond to TF-specific binding profiles or were data-type specific; we maintained the CORE and Unvalidated collections. We computed and compiled TF binding profiles obtained from CAP-SELEX ( 14 ), NCAP-SELEX ( 30 ), SELEX-seq ( 31 ), PBMs ( 32 ), ChIP-seq ( 33–36 ) and DAP-seq experiments from ReMap 2022 ( 36 ) and GEO ( 37 ), and ChIP-exo ( 38 ) data ( Supplementary Data 1 - Text for detailed list of datasets and method details). After manual curation of these profiles to confirm orthogonal supports in the literature, we augmented the CORE collection with 341 new binding profiles for TFs in four taxa (Table 1 ; Figure 1 ): 148 profiles in plants (a 24% expansion for this taxon), 101 profiles in vertebrates (a 13% expansion), 85 profiles in urochordates (only one motif was present since the second release of JASPAR in 2006 ( 27 )), and seven profiles in insects (a 5% expansion).…”

“…We exhaustively revised the metadata to update information about the TF names, the structural class and family of the TF DBDs (following TFClass ( 39 )), and links to external databases such as UniProt ( 40 ), ReMap ( 36 ), UniBind ( 15 , 16 ) and DNA Readout Viewer ( 41 ), whenever possible. Finally, we removed 32 profiles from the CORE collection (22 plant, 6 vertebrate and 4 fungi profiles) as they corresponded to synonyms of already present TF profiles, had low information content, or were derived from consensus strings (Table 1 ).…”

“…For the 9th release of the JASPAR database, we substantially expanded the JASPAR CORE collection by 19% (341 added motifs). The newly introduced TF binding profiles were obtained after manual curation of PFMs predicted de novo from >3500 ChIP-seq/-exo datasets (from ReMap 2022 ( 36 ) and GEO ( 61 )) or retrieved from publically available repositories. While we continued our commitment to provide non-redundant, high-quality TF binding profiles for TFs across six taxa, this release comes with an important increase in the number of profiles for urochordata, with 86 PFMs available when JASPAR has contained a single one since 2006 ( 27 ).…”

Identification of genetic variants that impact gene co-expression relationships using large-scale single-cell data

“…For 18 of the 19 SNP–eGene pairs, we found enrichment among the associated co-eGenes for at least one GO term ( Supplementary Table 14 ). Moreover, we assessed potential common TFs regulating the shared function of these co-eGenes using ChIP-seq data processed by ReMap 2022 (33) and found enrichment of TF binding sites among the co-eGenes for 7 of the 19 SNP–eGene pairs ( Supplementary Table 15 ). For four of the SNP–eGene pairs, the co-eQTL SNP itself or a SNP in high linkage disequilibrium (LD) (R 2 ≥ 0.9) lay in the binding region of the enriched TFs ( Supplementary Table 15 ), making these likely candidates for the direct regulator.…”

“…Next, we explored if these co-eGene sets were enriched for certain TF binding sites. TF annotations were taken from ChIP-seq peaks processed in the ReMap 2022 database (33), which we filtered for cell lines associated with blood cell lines. We tested the overlap of these peaks with the promoter regions of the co-eGenes tested, defining the promoter region as the region 2kB upstream and downstream of the first transcription start site of the gene.…”