SIGNOR: a database of causal relationships between biological entities

Abstract

Assembly of large biochemical networks can be achieved by confronting new cell-specific experimental data with an interaction subspace constrained by prior literature evidence. The SIGnaling Network Open Resource, SIGNOR (available on line at http://signor.uniroma2.it), was developed to support such a strategy by providing a scaffold of prior experimental evidence of causal relationships between biological entities. The core of SIGNOR is a collection of approximately 12 000 manually-annotated causal relationships between over 2800 human proteins participating in signal transduction. Other entities annotated in SIGNOR are complexes, chemicals, phenotypes and stimuli. The information captured in SIGNOR can be represented as a signed directed graph illustrating the activation/inactivation relationships between signalling entities. Each entry is associated to the post-translational modifications that cause the activation/inactivation of the target proteins. More than 4900 modified residues causing a change in protein concentration or activity have been curated and linked to the modifying enzymes (about 351 human kinases and 94 phosphatases). Additional modifications such as ubiquitinations, sumoylations, acetylations and their effect on the modified target proteins are also annotated. This wealth of structured information can support experimental approaches based on multi-parametric analysis of cell systems after physiological or pathological perturbations and to assemble large logic models.

Streamlined Tandem Mass Tag (SL-TMT) Protocol: An Efficient Strategy for Quantitative (Phospho)proteome Profiling Using Tandem Mass Tag-Synchronous Precursor Selection-MS3

“…Information gained from these databases allowed for the classification of proteins based on their molecular function, cellular compartment, associated biological pathways and protein-protein interactions, among other characteristics. For phosphorylation site analysis, several on-line programs were also available to explore further phosphorylation sites, related kinases, and associated networks, including Signor (42), Networkin/Kinforest (43), and PhosphoSitePlus (44). In particular, PhosphoSitePlus incorporates an expansive array of tools, such as motif searching and a sequence logo generator.…”

Identification of critical paralog groups with indispensable roles in the regulation of signaling flow

“…Our work may be affected by the database of choice. To the best of our knowledge SignaLink 2 has the most straightforward pathway and cross-talk definition13 but our analysis should be tested in the future using other pathway curation sources like Reactome79 or Signor80. Information about cross-talk proteins is the determining factor in the analysis of other datasets because if a protein from a paralog group was involved in a cross-talk then the group was counted as a critical paralog group.…”

Network-based integration of multi-omics data for prioritizing cancer genes

“…The three sources included the databases Signor (Perfetto et al , 2016), Signalink (Fazekas et al , 2013) and the functional directed interaction network defined by Wu et al (2010), who combined interactions reported in various databases, including Kegg (Kanehisa et al , 2017), Panther (Mi et al , 2017), NCI (Schaefer et al , 2009) and others, offering a large coverage of validated functional interactions. We also downloaded miRNA-gene interactions from miRTarBase (Chou et al , 2016), a database that contains experimentally validated interactions between miRNA and target genes.…”