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Abstract Background Deciphering gene regulatory networks by in silico approaches is a crucial step in the study of the molecular perturbations that occur in diseases. The development of regulatory maps is a tedious process requiring the comprehensive integration of various evidences scattered over biological databases. Thus, the research community would greatly benefit from having a unified database storing known and predicted molecular interactions. Furthermore, given the intrinsic complexity of the data, the development of new tools offering integrated and meaningful visualizations of molecular interactions is necessary to help users drawing new hypotheses without being overwhelmed by the density of the subsequent graph. Results We extend the previously developed TranscriptomeBrowser database with a set of tables containing 1,594,978 human and mouse molecular interactions. The database includes: (i) predicted regulatory interactions (computed by scanning vertebrate alignments with a set of 1,213 position weight matrices), (ii) potential regulatory interactions inferred from systematic analysis of ChIP-seq experiments, (iii) regulatory interactions curated from the literature, (iv) predicted post-transcriptional regulation by micro-RNA, (v) protein kinase-substrate interactions and (vi) physical protein-protein interactions. In order to easily retrieve and efficiently analyze these interactions, we developed In-teractomeBrowser, a graph-based knowledge browser that comes as a plug-in for Transcriptome-Browser. The first objective of InteractomeBrowser is to provide a user-friendly tool to get new insight into any gene list by providing a context-specific display of putative regulatory and physical interactions. To achieve this, InteractomeBrowser relies on a "cell compartments-based layout" that makes use of a subset of the Gene Ontology to map gene products onto relevant cell compartments. This layout is particularly powerful for visual integration of heterogeneous biological information and is a productive avenue in generating new hypotheses. The second objective of InteractomeBrowser is to fill the gap between interaction databases and dynamic modeling. It is thus compatible with the network analysis software Cytoscape and with the Gene Interaction Network simulation software (GINsim). We provide examples underlying the benefits of this visualization tool for large gene set analysis related to thymocyte differentiation. Conclusions The InteractomeBrowser plugin is a powerful tool to get quick access to a knowledge database that includes both predicted and validated molecular interactions. InteractomeBrowser is available through the TranscriptomeBrowser framework and can be found at: http://tagc.univ-mrs.fr/tbrowser/. Our database is updated on a regular basis.

Summary To better understand why human neonates show a poor response to intracellular pathogens, we compared gene expression and histone modification profiles of neonatal naive CD8 + T cells with that of their adult counterparts. We found that neonatal lymphocytes have a distinct epigenomic landscape associated with a lower expression of genes involved in T cell receptor (TCR) signaling and cytotoxicity and a higher expression of genes involved in the cell cycle and innate immunity. Functional studies corroborated that neonatal CD8 + T cells are less cytotoxic, transcribe antimicrobial peptides, and produce reactive oxygen species. Altogether, our results show that neonatal CD8 + T cells have a specific genetic program biased toward the innate immune response. These findings will contribute to better diagnosis and management of the neonatal immune response. [ABSTRACT FROM AUTHOR]

Divergent transcription is a wide-spread phenomenon in mammals. For instance, short bidirectional transcripts are a hallmark of active promoters, while longer transcripts can be detected antisense from active genes in conditions where the RNA degradation machinery is inhibited. Moreover, many described long non-coding RNAs (lncRNAs) are transcribed antisense from coding gene promoters. However, the general significance of divergent lncRNA/mRNA gene pair transcription is still poorly understood. Here, we used strandspecific RNA-seq with high sequencing depth to thoroughly identify antisense transcripts from coding gene promoters in primary mouse tissues. Results We found that a substantial fraction of coding-gene promoters sustain divergent transcription of long non-coding RNA (lncRNA)/mRNA gene pairs. Strikingly, upstream antisense transcription is significantly associated with genes related to transcriptional regulation and development. Their promoters share several characteristics with those of transcriptional developmental genes, including very large CpG islands, high degree of conservation and epigenetic regulation in ES cells. In-depth analysis revealed a unique GC skew profile at these promoter regions, while the associated coding genes were found to have large first exons, two genomic features that might enforce bidirectional transcription. Finally, genes associated with antisense transcription harbor specific H3K79me2 epigenetic marking and RNA polymerase II enrichment profiles linked to an intensified rate of early transcriptional elongation. Conclusions We concluded that promoters of a class of transcription regulators are characterized by a specialized transcriptional control mechanism, which is directly coupled to relaxed bidirectional transcription. [ABSTRACT FROM AUTHOR]

Background: Cerebral malaria (CM), a reversible encephalopathy affecting young children, is a medical emergency requiring rapid clinical assessment and treatment. However, understanding of the genes/proteins and the biological pathways involved in the disease outcome is still limited., Methods: We have performed a whole transcriptomic analysis of blood samples from Malian children with CM or uncomplicated malaria (UM). Hierarchical clustering and pathway, network, and upstream regulator analyses were performed to explore differentially expressed genes (DEGs). We validated gene expression for 8 genes using real-time quantitative PCR (RT-qPCR). Plasma levels were measured for IP-10/CXCL10 and IL-18., Results: A blood RNA signature including 538 DEGs (∣FC | ≥2.0, adjusted P value ≤ 0.01) allowed to discriminate between CM and UM. Ingenuity Pathway Analysis (IPA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed novel genes and biological pathways related to immune/inflammatory responses, erythrocyte alteration, and neurodegenerative disorders. Gene expressions of CXCL10, IL12RB2, IL18BP, IL2RA, AXIN2, and NET were significantly lower in CM whereas ARG1 and SLC6A9 were higher in CM compared to UM. Plasma protein levels of IP-10/CXCL10 were significantly lower in CM than in UM while levels of IL-18 were higher. Interestingly, among children with CM, those who died from a complication of malaria tended to have higher concentrations of IP-10/CXCL10 and IFN- γ than those who recovered., Conclusions: This study identified some new factors and mechanisms that play crucial roles in CM and characterized their respective biological pathways as well as some upstream regulators., Competing Interests: The authors do not have commercial or other associations that might pose a conflict of interest., (Copyright © 2020 Sandrine Cabantous et al.)

ReMap (http://remap.univ-amu.fr) aims to provide the largest catalogs of high-quality regulatory regions resulting from a large-scale integrative analysis of hundreds of transcription factors and regulators from DNA-binding experiments in Human and Arabidopsis (Arabidopsis thaliana). In this 2020 update of ReMap we have collected, analyzed and retained after quality control 2764 new human ChIP-seq and 208 ChIP-exo datasets available from public sources. The updated human atlas totalize 5798 datasets covering a total of 1135 transcriptional regulators (TRs) with a catalog of 165 million (M) peaks. This ReMap update comes with two unique Arabidopsis regulatory catalogs. First, a catalog of 372 Arabidopsis TRs across 2.6M peaks as a result of the integration of 509 ChIP-seq and DAP-seq datasets. Second, a catalog of 33 histone modifications and variants across 4.5M peaks from the integration of 286 ChIP-seq datasets. All catalogs are made available through track hubs at Ensembl and UCSC Genome Browsers. Additionally, this update comes with a new web framework providing an interactive user-interface, including improved search features. Finally, full programmatically access to the underlying data is available using a RESTful API together with a new R Shiny interface for a TRs binding enrichment analysis tool., (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)