PhenomiR: a knowledgebase for microRNA expression in diseases and biological processes

PhenomiR is a comprehensive database of 542 studies reporting deregulation of miRNAs allowing large-scale statistical analysis of miRNA expression changes

Descriptions of Spatial Operations – Recent Approaches and Community Feedback

Progress in the technical provision of spatial operations as loosely-coupled interoperable web services requires a corresponding development of standardisation in their description. Operation discovery, usage and interpretation of results require more information on what a spatial operation does than just their input and output interface specifications. Geooperators and WPS profiles have been proposed for addressing operation descriptions for different operational perspectives. Geooperators have been developed mostly for supporting operation discovery through defining alternative perspectives such as a geodata, legacy GIS, formal or technical perspective. These act as filters in the discovery process. WPS profiles provide a hierarchical approach to define the concept underlying an operation and, in more specific profiles, the syntactic interface of the operation. Both approaches require community engagement for reaching an agreed set of documented operations. We report on a discussion of these approaches and the larger framework of a geoprocessing community platform from a workshop held at the AGILE International Conference on Geographic Information Science in Lisbon in 2015. At the workshop two presentations provided insights in different contexts of use of online geoprocessing. After detailed introductions to the two operation descriptions approaches, two breakout sessions were held. In the breakout sessions operation descriptions and technical developments in the field were discussed. This article summarizes the discussion that took place at the workshop with the intention to involve the extended community in the discourse on operation descriptions

The Mouse Functional Genome Database (MfunGD): functional annotation of proteins in the light of their cellular context

MfunGD () provides a resource for annotated mouse proteins and their occurrence in protein networks. Manual annotation concentrates on proteins which are found to interact physically with other proteins. Accordingly, manually curated information from a protein–protein interaction database (MPPI) and a database of mammalian protein complexes is interconnected with MfunGD. Protein function annotation is performed using the Functional Catalogue (FunCat) annotation scheme which is widely used for the analysis of protein networks. The dataset is also supplemented with information about the literature that was used in the annotation process as well as links to the SIMAP Fasta database, the Pedant protein analysis system and cross-references to external resources. Proteins that so far were not manually inspected are annotated automatically by a graphical probabilistic model and/or superparamagnetic clustering. The database is continuously expanding to include the rapidly growing amount of functional information about gene products from mouse. MfunGD is implemented in GenRE, a J2EE-based component-oriented multi-tier architecture following the separation of concern principle

CORUM: the comprehensive resource of mammalian protein complexes—2009

CORUM is a database that provides a manually curated repository of experimentally characterized protein complexes from mammalian organisms, mainly human (64%), mouse (16%) and rat (12%). Protein complexes are key molecular entities that integrate multiple gene products to perform cellular functions. The new CORUM 2.0 release encompasses 2837 protein complexes offering the largest and most comprehensive publicly available dataset of mammalian protein complexes. The CORUM dataset is built from 3198 different genes, representing ∼16% of the protein coding genes in humans. Each protein complex is described by a protein complex name, subunit composition, function as well as the literature reference that characterizes the respective protein complex. Recent developments include mapping of functional annotation to Gene Ontology terms as well as cross-references to Entrez Gene identifiers. In addition, a ‘Phylogenetic Conservation’ analysis tool was implemented that analyses the potential occurrence of orthologous protein complex subunits in mammals and other selected groups of organisms. This allows one to predict the occurrence of protein complexes in different phylogenetic groups. CORUM is freely accessible at (http://mips.helmholtz-muenchen.de/genre/proj/corum/index.html)

The Negatome database: a reference set of non-interacting protein pairs

The Negatome is a collection of protein and domain pairs that are unlikely to be engaged in direct physical interactions. The database currently contains experimentally supported non-interacting protein pairs derived from two distinct sources: by manual curation of literature and by analyzing protein complexes with known 3D structure. More stringent lists of non-interacting pairs were derived from these two datasets by excluding interactions detected by high-throughput approaches. Additionally, non-interacting protein domains have been derived from the stringent manual and structural data, respectively. The Negatome is much less biased toward functionally dissimilar proteins than the negative data derived by randomly selecting proteins from different cellular locations. It can be used to evaluate protein and domain interactions from new experiments and improve the training of interaction prediction algorithms. The Negatome database is available at http://mips.helmholtz-muenchen.de/proj/ppi/negatome

Mutation Analysis of NR5A1 Encoding Steroidogenic Factor 1 in 77 Patients with 46, XY Disorders of Sex Development (DSD) Including Hypospadias

BACKGROUND: Mutations of the NR5A1 gene encoding steroidogenic factor-1 have been reported in association with a wide spectrum of 46,XY DSD (Disorder of Sex Development) phenotypes including severe forms of hypospadias. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the frequency of NR5A1 gene mutations in a large series of patients presenting with 46,XY DSD and hypospadias. Based on their clinical presentation 77 patients were classified either as complete or partial gonadal dysgenesis (uterus seen at genitography and/or surgery, n = 11), ambiguous external genitalia without uterus (n = 33) or hypospadias (n = 33). We identified heterozygous NR5A1 mutations in 4 cases of ambiguous external genitalia without uterus (12.1%; p.Trp279Arg, pArg39Pro, c.390delG, c140_141insCACG) and a de novo missense mutation in one case with distal hypospadias (3%; p.Arg313Cys). Mutant proteins showed reduced transactivation activity and mutants p.Arg39Pro and p.Arg313Cys did not synergize with the GATA4 cofactor to stimulate reporter gene activity, although they retained their ability to physically interact with the GATA4 protein. CONCLUSIONS/SIGNIFICANCE: Mutations in NR5A1 were observed in 5/77 (6.5%) cases of 46,XY DSD including hypospadias. Excluding the cases of 46,XY gonadal dysgenesis the incidence of NR5A1 mutations was 5/66 (7.6%). An individual with isolated distal hypopadias carried a de novo heterozygous missense mutation, thus extending the range of phenotypes associated with NR5A1 mutations and suggesting that this group of patients should be screened for NR5A1 mutations

COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms.

Funder: Bundesministerium für Bildung und ForschungFunder: Bundesministerium für Bildung und Forschung (BMBF)We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective

Alles nur symbolisch? Bilanz und Perspektiven der Erforschung symbolischer Kommunikation

Brauner C, Stollberg-Rilinger B, Neu T, eds. Alles nur symbolisch? Bilanz und Perspektiven der Erforschung symbolischer Kommunikation. Köln u.a.: Böhlau; 2013