RNADisease v4.0: an updated resource of RNA-associated diseases, providing RNA-disease analysis, enrichment and prediction.

Numerous studies have shown that RNA plays an important role in the occurrence and development of diseases, and RNA-disease associations are not limited to noncoding RNAs in mammals but also exist for protein-coding RNAs. Furthermore, RNA-associated diseases are found across species including plants and nonmammals. To better analyze diseases at the RNA level and facilitate researchers in exploring the pathogenic mechanism of diseases, we decided to update and change MNDR v3.0 to RNADisease v4.0, a repository for RNA-disease association (http://www.rnadisease.org/ or http://www.rna-society.org/mndr/). Compared to the previous version, new features include: (i) expanded data sources and categories of species, RNA types, and diseases; (ii) the addition of a comprehensive analysis of RNAs from thousands of high-throughput sequencing data of cancer samples and normal samples; (iii) the addition of an RNA-disease enrichment tool and (iv) the addition of four RNA-disease prediction tools. In summary, RNADisease v4.0 provides a comprehensive and concise data resource of RNA-disease associations which contains a total of 3 428 058 RNA-disease entries covering 18 RNA types, 117 species and 4090 diseases to meet the needs of biological research and lay the foundation for future therapeutic applications of diseases.

Cellinker: a platform of ligand-receptor interactions for intercellular communication analysis.

MOTIVATION: Ligand-receptor (L-R) interactions mediate cell adhesion, recognition and communication and play essential roles in physiological and pathological signaling. With the rapid development of single-cell RNA sequencing (scRNA-seq) technologies, systematically decoding the intercellular communication network involving L-R interactions has become a focus of research. Therefore, construction of a comprehensive, high-confidence and well-organized resource to retrieve L-R interactions in order to study the functional effects of cell-cell communications would be of great value. RESULTS: In this study, we developed Cellinker, a manually curated resource of literature-supported L-R interactions that play roles in cell-cell communication. We aimed to provide a useful platform for studies on cell-cell communication mediated by L-R interactions. The current version of Cellinker documents over 3,700 human and 3,200 mouse L-R protein-protein interactions (PPIs) and embeds a practical and convenient webserver with which researchers can decode intercellular communications based on scRNA-seq data. And over 400 endogenous small molecule (sMOL) related L-R interactions were collected as well. Moreover, to help with research on coronavirus (CoV) infection, Cellinker collects information on 16 L-R PPIs involved in CoV-human interactions (including 12 L-R PPIs involved in SARS-CoV-2 infection). In summary, Cellinker provides a user-friendly interface for querying, browsing and visualizing L-R interactions as well as a practical and convenient web tool for inferring intercellular communications based on scRNA-seq data. We believe this platform could promote intercellular communication research and accelerate the development of related algorithms for scRNA-seq studies. AVAILABILITY: Cellinker is available at http://www.rna-society.org/cellinker/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Profiling neuroendocrine gene expression changes following fadrozole-induced estrogen decline in the female goldfish.

Teleost fish represent unique models to study the role of neuroestrogens because of the extremely high activity of brain aromatase (AroB; the product of cyp19a1b). Aromatase respectively converts androstenedione and testosterone to estrone and 17beta-estradiol (E2). Specific inhibition of aromatase activity by fadrozole has been shown to impair estrogen production and influence neuroendocrine and reproductive functions in fish, amphibians, and rodents. However, very few studies have identified the global transcriptomic response to fadrozole-induced decline of estrogens in a physiological context. In our study, sexually mature prespawning female goldfish were exposed to fadrozole (50 mcirog/l) in March and April when goldfish have the highest AroB activity and maximal gonadal size. Fadrozole treatment significantly decreased serum E2 levels (4.7 times lower; P = 0.027) and depressed AroB mRNA expression threefold in both the telencephalon (P = 0.021) and the hypothalamus (P = 0.006). Microarray expression profiling of the telencephalon identified 98 differentially expressed genes after fadrozole treatment (q value <0.05). Some of these genes have shown previously to be estrogen responsive in either fish or other species, including rat, mouse, and human. Gene ontology analysis together with functional annotations revealed several regulatory themes for physiological estrogen action in fish brain that include the regulation of calcium signaling pathway and autoregulation of estrogen receptor action. Real-time PCR verified microarray data for decreased (activin-betaA) or increased (calmodulin, ornithine decarboxylase 1) mRNA expression. These data have implications for our understanding of estrogen actions in the adult vertebrate brain.