SIGNOR 3.0, the SIGnaling network open resource 3.0: 2022 update

Abstract

The SIGnaling Network Open Resource (SIGNOR 3.0, https://signor.uniroma2.it) is a public repository that captures causal information and represents it according to an ‘activity-flow’ model. SIGNOR provides freely-accessible static maps of causal interactions that can be tailored, pruned and refined to build dynamic and predictive models. Each signaling relationship is annotated with an effect (up/down-regulation) and with the mechanism (e.g. binding, phosphorylation, transcriptional activation, etc.) causing the regulation of the target entity. Since its latest release, SIGNOR has undergone a significant upgrade including: (i) a new website that offers an improved user experience and novel advanced search and graph tools; (ii) a significant content growth adding up to a total of approx. 33,000 manually-annotated causal relationships between more than 8900 biological entities; (iii) an increase in the number of manually annotated pathways, currently including pathways deregulated by SARS-CoV-2 infection or involved in neurodevelopment synaptic transmission and metabolism, among others; (iv) additional features such as new model to represent metabolic reactions and a new confidence score assigned to each interaction.

Curation of causal interactions mediated by genes associated to autism accelerates the understanding of gene-phenotype relationships underlying neurodevelopmental disorders

“…Curators of the SIGnaling Network Open Resource (SIGNOR) (Lo Surdo et al , 2022) manually annotate causal interactions according to an ‘activity-flow’ model (protein A up-/down-regulates protein B) (Cesareni et al , 2021) (Figure 1A). The resource captures signaling relationships between a variety of human biological entities, including biomolecules (proteins, macromolecular complexes, small molecules etc.…”

“…Interactions in SIGNOR are assigned a significance score, ranging from 0.1 to 1 and form a large and intricate interactome of 9000 entities connected by 34,200 edges (November 2022) (Figure 1A). SIGNOR causal interactome is a large connected component with few satellite clusters (Lo Surdo et al , 2022). In parallel, SIGNOR curators also annotate pathways, which are subgraphs of the causal interactome providing a description of how a cell responds to specific environmental cues (Figure 1A).…”

“…Starting from highly ranked genes we have looked by standard Medline searches for published information reporting the consequences of disrupting gene function on downstream proteins. The curation of the reported experimental evidence was according to the SIGNOR database curation standards (Lo Surdo et al , 2022).…”

The 2023 Nucleic Acids Research Database Issue and the online molecular biology database collection

“…Elsewhere, the cornerstone resource in pathway analysis KEGG ( 41 ) contributes an update reporting on new genome and taxonomy browsers, while the equally foundational database STRING ( 42 ) reports on new co-expression data sources, improved interaction confidence estimates and the ability to process whole new genomes. Other well-used returning databases include MIBiG, whose update paper ( 43 ) has an interesting focus on annotation, including online ‘annotathons’; and SIGNOR ( 44 ) which has new data, a new interface, and new links to related projects focusing on diseases, including COVID-19. Finally, the new CovInter database ( 45 ) captures data on interactions between Coronavirus RNAs and host proteins.…”

Monocytes Subsets Altered Distribution and Dysregulated Plasma hsa-miR-21-5p and hsa- miR-155-5p in HCV-Linked Liver Cirrhosis Progression to Hepatocellular Carcinoma

“…The monocyte cluster of differentiation 14 (CD14) [23] is identi ed by Uniport and GeneCards in silico databases. CD14 is involved in mediating the innate immune response, on chromosome 5 reverse strand, activating the nuclear factor kappa-B cell (NF-K B), few cytokine secretions and the in ammatory response [24], as identi ed via the curated database SIGnaling Network Open Resource; Signor3.0 [25].…”