Nuclear Receptor Signaling Atlas: Opening Access to the Biology of Nuclear Receptor Signaling Pathways

Abstract

Signaling pathways involving nuclear receptors (NRs), their ligands and coregulators, regulate tissue-specific transcriptomes in diverse processes, including development, metabolism, reproduction, the immune response and neuronal function, as well as in their associated pathologies. The Nuclear Receptor Signaling Atlas (NURSA) is a Consortium focused around a Hub website (www.nursa.org) that annotates and integrates diverse ‘omics datasets originating from the published literature and NURSA-funded Data Source Projects (NDSPs). These datasets are then exposed to the scientific community on an Open Access basis through user-friendly data browsing and search interfaces. Here, we describe the redesign of the Hub, version 3.0, to deploy “Web 2.0” technologies and add richer, more diverse content. The Molecule Pages, which aggregate information relevant to NR signaling pathways from myriad external databases, have been enhanced to include resources for basic scientists, such as post-translational modification sites and targeting miRNAs, and for clinicians, such as clinical trials. A portal to NURSA’s Open Access, PubMed-indexed journal Nuclear Receptor Signaling has been added to facilitate manuscript submissions. Datasets and information on reagents generated by NDSPs are available, as is information concerning periodic new NDSP funding solicitations. Finally, the new website integrates the Transcriptomine analysis tool, which allows for mining of millions of richly annotated public transcriptomic data points in the field, providing an environment for dataset re-use and citation, bench data validation and hypothesis generation. We anticipate that this new release of the NURSA database will have tangible, long term benefits for both basic and clinical research in this field.

Estrogen receptor alpha (ERα)–mediated coregulator binding and gene expression discriminates the toxic ERα agonist diethylstilbestrol (DES) from the endogenous ERα agonist 17β-estradiol (E2)

“…Gene ontology and pathway analysis were carried out using the Consensus Path Database (cpdb) tool (Kamburov et al 2011 ). For NR pathway analysis, lists containing all cpdb and the top 100 genes of the NURSA data base Transcriptomine (Consensome) (Becnel et al 2015 ) were also used. In all cases, only gene ontology and pathways with p values lower than 0.05 were included for analysis.…”

Chemical Screening of Nuclear Receptor Modulators

“…Phenotypic chemical screening uses assays to detect the effects on biological phenomena that involve nuclear receptors (e.g., cell viability, alteration of cellular morphology) [ 17 , 24 ]. Cell proliferation assay is a very common screening method, and many kits and measuring instruments are available for its evaluation [ 12 , 13 , 74 ].…”

“…Forty-eight types of nuclear receptors have been found in humans, and 25 of these are orphan receptors with unknown endogenous ligands [ 22 ]. The ligand-dependent action of nuclear receptors includes that the activated receptors translocate into the nucleus, bind to the specific sites of DNA, and regulate the target gene expression to elicit various events, such as cell proliferation, differentiation, reproduction, metabolism, and the maintenance of homeostasis [ 23 , 24 ]. Some orphan receptors are known to act constitutively as transcription-promoting factors and to play roles in releasing transcriptional repression [ 25 ].…”

Discovering relationships between nuclear receptor signaling pathways, genes, and tissues in Transcriptomine

“…Where available, we adopted mappings curated by the International Union of Pharmacology Guide to Pharmacology (GtoPdb) resource (134) or DrugBank (135). Where mappings were not available from either of these resources, we created these de novo based on biocuration of the literature on a specific ligand or regulatory small molecule (136).…”