JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) for TFs across multiple species in six taxonomic groups. In this 8th release of JASPAR, the CORE collection has been expanded with 245 new PFMs (169 for vertebrates, 42 for plants, 17 for nematodes, 10 for insects, and 7 for fungi), and 156 PFMs were updated (125 for vertebrates, 28 for plants and 3 for insects). These new profiles represent an 18% expansion compared to the previous release. JASPAR 2020 comes with a novel collection of unvalidated TF-binding profiles for which our curators did not find orthogonal supporting evidence in the literature. This collection has a dedicated web form to engage the community in the curation of unvalidated TF-binding profiles. Moreover, we created a Q&A forum to ease the communication between the user community and JASPAR curators. Finally, we updated the genomic tracks, inference tool, and TF-binding profile similarity clusters. All the data is available through the JASPAR website, its associated RESTful API, and through the JASPAR2020 R/Bioconductor package.

https://hal.archives-ouvertes.fr/hal-02365013/document

JASPAR 2020: update of the open-access database of transcription factor binding profiles

The laboratory mouse shares the majority of its protein-coding genes with humans, making it the premier model organism in biomedical research, yet the two mammals differ in significant ways. To gain greater insights into both shared and species-specific transcriptional and cellular regulatory programs in the mouse, the Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types. By comparing with the human genome, we not only confirm substantial conservation in the newly annotated potential functional sequences, but also find a large degree of divergence of sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization. Our results illuminate the wide range of evolutionary forces acting on genes and their regulatory regions, and provide a general resource for research into mammalian biology and mechanisms of human diseases.

A comparative encyclopedia of DNA elements in the mouse genome

The Encyclopedia of DNA Elements (ENCODE) is an ongoing collaborative research project aimed at identifying all the functional elements in the human and mouse genomes. Data generated by the ENCODE consortium are freely accessible at the ENCODE portal (https://www.encodeproject.org/), which is developed and maintained by the ENCODE Data Coordinating Center (DCC). Since the initial portal release in 2013, the ENCODE DCC has updated the portal to make ENCODE data more findable, accessible, interoperable and reusable. Here, we report on recent updates, including new ENCODE data and assays, ENCODE uniform data processing pipelines, new visualization tools, a dataset cart feature, unrestricted public access to ENCODE data on the cloud (Amazon Web Services open data registry, https://registry.opendata.aws/encode-project/) and more comprehensive tutorials and documentation.

New developments on the Encyclopedia of DNA Elements (ENCODE) data portal.

For more than 100 years, the fruit fly Drosophila melanogaster has been one of the most studied model organisms. Here, we present a single-cell atlas of the adult fly, Tabula Drosophilae, that includes 580,000 nuclei from 15 individually dissected sexed tissues as well as the entire head and body, annotated to >250 distinct cell types. We provide an in-depth analysis of cell type–related gene signatures and transcription factor markers, as well as sexual dimorphism, across the whole animal. Analysis of common cell types between tissues, such as blood and muscle cells, reveals rare cell types and tissue-specific subtypes. This atlas provides a valuable resource for the Drosophila community and serves as a reference to study genetic perturbations and disease models at single-cell resolution. Description Cell type diversity in a whole fly The fruit fly Drosophila melanogaster has served as a premier model organism for discovering fundamental and evolutionarily conserved biological mechanisms. Combining recent advances in single-cell sequencing with powerful fly genetic tools holds great promise for making further discoveries. Li et al. present a single-cell atlas of the entire adult fly that includes 580,000 cells and more than 250 annotated cell types. Cells from the head and body recapitulated cell types from 15 dissected tissues. In-depth analyses revealed rare cell types, cell-type-specific gene signatures, and sexual dimorphism. This atlas provides a resource for the Drosophila community to study genetic perturbations and diseases at single-cell resolution. —BAP A single-nucleus transcriptomic map reveals more than 250 distinct cell types in the entire adult Drosophila melanogaster. INTRODUCTION Drosophila melanogaster has had a fruitful history in biological research because it has contributed to many key discoveries in genetics, development, and neurobiology. The fruit fly genome contains ~14,000 protein-coding genes, ~63% of which have human orthologs. Single-cell RNA-sequencing has recently been applied to multiple Drosophila tissues and developmental stages. However, these data have been generated by different laboratories on different genetic backgrounds with different dissociation protocols and sequencing platforms, which has hindered the systematic comparison of gene expression across cells and tissues. RATIONALE We aimed to establish a cell atlas for the entire adult Drosophila with the same genetic background, dissociation protocol, and sequencing platform to (i) obtain a comprehensive categorization of cell types, (ii) integrate single-cell transcriptome data with existing knowledge about gene expression and cell types, (iii) systematically compare gene expression across the entire organism and between males and females, and (iv) identify cell type–specific markers across the entire organism. We chose single-nucleus RNA-sequencing (snRNA-seq) to circumvent the difficulties of dissociating cells that are embedded in the cuticle (e.g., sensory neurons) or that are multinucleated (e.g., muscle cells). We took two complementary strategies: sequencing nuclei from dissected tissues to know the identity of the tissue source and sequencing nuclei from the entire head and body to ensure that all cells are sampled. Experts from 40 laboratories participated in crowd annotation to assign transcriptomic cell types with the best knowledge available. RESULTS We sequenced 570,000 cells using droplet-based 10x Genomics from 15 dissected tissues as well as whole heads and bodies, separately in females and males. We also sequenced 10,000 cells from dissected tissues using the plate-based Smart-seq2 platform, providing deeper coverage per cell. We developed reproducible analysis pipelines using NextFlow and implemented a distributed cell-type annotation system with controlled vocabularies in SCope. Crowd-based annotations of transcriptomes from dissected tissues identified 17 main cell categories and 251 detailed cell types linked to FlyBase ontologies. Many of these cell types are characterized for the first time, either because they emerged only after increasing cell coverage or because they reside in tissues that had not been previously subjected to scRNA-seq. The excellent correspondence of transcriptomic clusters from whole body and dissected tissues allowed us to transfer annotations and identify a few cuticular cell types not detected in individual tissues. Cross-tissue analysis revealed location-specific subdivisions of muscle cells and heterogeneity within blood cells. We then determined cell type–specific marker genes and transcription factors with different specificity levels, enabling the construction of gene regulatory networks. Finally, we explored sexual dimorphism, finding a link between sex-biased expression and the presence of doublesex, and investigated tissue dynamics through trajectory analyses. CONCLUSION Our Fly Cell Atlas (FCA) constitutes a valuable resource for the Drosophila community as a reference for studies of gene function at single-cell resolution. All the FCA data are freely available for further analysis through multiple portals and can be downloaded for custom analyses using other single-cell tools. The ability to annotate cell types by sequencing the entire head and body will facilitate the use of Drosophila in the study of biological processes and in modeling human diseases at a whole-organism level with cell-type resolution. All data with annotations can be accessed from www.flycellatlas.org, which provides links to SCope, ASAP, and cellxgene portals. Tabula Drosophilae. In this single-cell atlas of the adult fruit fly, 580,000 cells were sequenced and >250 cell types were annotated. They are from 15 individually dissected sexed tissues as well as the entire head and body. All data are freely available for visualization and download, with featured analyses shown at the bottom right.

/pdf/fly-cell-atlas-a-single-nucleus-transcriptomic-atlas-of-the-22l3kzu4.pdf

Fly Cell Atlas: A single-nucleus transcriptomic atlas of the adult fruit fly

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.

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

To develop a catalog of regulatory sites in two major model organisms, Drosophila melanogaster and Caenorhabditis elegans, the modERN (model organism Encyclopedia of Regulatory Networks) consortium has systematically assayed the binding sites of transcription factors (TFs). Combined with data produced by our predecessor, modENCODE (Model Organism ENCyclopedia Of DNA Elements), we now have data for 262 TFs identifying 1.23 M sites in the fly genome and 217 TFs identifying 0.67 M sites in the worm genome. Because sites from different TFs are often overlapping and tightly clustered, they fall into 91,011 and 59,150 regions in the fly and worm, respectively, and these binding sites span as little as 8.7 and 5.8 Mb in the two organisms. Clusters with large numbers of sites (so-called high occupancy target, or HOT regions) predominantly associate with broadly expressed genes, whereas clusters containing sites from just a few factors are associated with genes expressed in tissue-specific patterns. All of the strains expressing GFP-tagged TFs are available at the stock centers, and the chromatin immunoprecipitation sequencing data are available through the ENCODE Data Coordinating Center and also through a simple interface (http://epic.gs.washington.edu/modERN/) that facilitates rapid accessibility of processed data sets. These data will facilitate a vast number of scientific inquiries into the function of individual TFs in key developmental, metabolic, and defense and homeostatic regulatory pathways, as well as provide a broader perspective on how individual TFs work together in local networks and globally across the life spans of these two key model organisms.

/pdf/the-modern-resource-genome-wide-binding-profiles-for-54yi80iip0.pdf

The modERN Resource: Genome-Wide Binding Profiles for Hundreds of Drosophila and Caenorhabditis elegans Transcription Factors

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The modERN Resource: Genome-Wide Binding Profiles for Hundreds of Drosophila and Caenorhabditis elegans Transcription Factors