A collaborative network analysis for the interpretation of transcriptomics data in Huntington's disease.

Rare diseases may affect the quality of life of patients and be life-threatening. Therapeutic opportunities are often limited, in part because of the lack of understanding of the molecular mechanisms underlying these diseases. This can be ascribed to the low prevalence of rare diseases and therefore the lower sample sizes available for research.

Drug repurposing in Rett and Rett-like syndromes: a promising yet underrated opportunity?

Rett syndrome (RTT) and Rett-like syndromes [i.e., CDKL5 deficiency disorder (CDD) and FOXG1-syndrome] represent rare yet profoundly impactful neurodevelopmental disorders (NDDs).

A novel insight into neurological disorders through HDAC6 protein-protein interactions.

Due to its involvement in physiological and pathological processes, histone deacetylase 6 (HDAC6) is considered a promising pharmaceutical target for several neurological manifestations. However, the exact regulatory role of HDAC6 in the central nervous system (CNS) is still not fully understood. Hence, using a semi-automated literature screening technique, we systematically collected HDAC6-protein interactions that are experimentally validated and reported in the CNS.

Copy number variant risk loci for schizophrenia converge on the BDNF pathway.

Objectives: Schizophrenia genetics is intricate, with common and rare variants' contributions not fully understood. Certain copy number variations (CNVs) elevate risk, pivotal for understanding mental disorder models. Despite CNVs' genome-wide distribution and variable gene and protein effects, we must explore beyond affected genes to interaction partners and molecular pathways.

Drug-target identification in COVID-19 disease mechanisms using computational systems biology approaches.

Introduction: The COVID-19 Disease Map project is a large-scale community effort uniting 277 scientists from 130 Institutions around the globe. We use high-quality, mechanistic content describing SARS-CoV-2-host interactions and develop interoperable bioinformatic pipelines for novel target identification and drug repurposing.

Methods: Extensive community work allowed an impressive step forward in building interfaces between Systems Biology tools and platforms.

Interactive neuroinflammation pathways and transcriptomics-based identification of drugs and chemical compounds for schizophrenia.

Objectives: Schizophrenia is a psychiatric disorder affecting 1% of the population. Accumulating evidence indicates that neuroinflammation is involved in the pathology of these disorders by altering neurodevelopmental processes and specifically affecting glutamatergic signalling and astrocytic functioning. The aim of this study was to curate interactive biological pathways involved in schizophrenia for the identification of novel pharmacological targets implementing pathway, gene ontology, and network analysis.

WikiPathways 2024: next generation pathway database.

WikiPathways (wikipathways.org) is an open-source biological pathway database. Collaboration and open science are pivotal to the success of WikiPathways.

Exploring pathway interactions to detect molecular mechanisms of disease: 22q11.2 deletion syndrome.

Background: 22q11.2 Deletion Syndrome (22q11DS) is a genetic disorder characterized by the deletion of adjacent genes at a location specified as q11.2 of chromosome 22, resulting in an array of clinical phenotypes including autistic spectrum disorder, schizophrenia, congenital heart defects, and immune deficiency.

Clustering Schizophrenia Genes by Their Temporal Expression Patterns Aids Functional Interpretation.

Background: Schizophrenia is a highly heritable brain disorder with a typical symptom onset in early adulthood. The 2-hit hypothesis posits that schizophrenia results from differential early neurodevelopment, predisposing an individual, followed by a disruption of later brain maturational processes that trigger the onset of symptoms.

Study Design: We applied hierarchical clustering to transcription levels of 345 genes previously linked to schizophrenia, derived from cortical tissue samples from 56 donors across the lifespan.

Fetal alcohol spectrum disorders and the risk of crime.

Fetal alcohol spectrum disorders (FASD) are an important preventable global health concern. FASD is an umbrella term describing a range of mild to severe cognitive and behavioral problems among individuals prenatally exposed to alcohol. Alcohol causes FASD by interfering with molecular pathways during fetal development involving increased oxidative stress, disturbed organ development, and change of epigenetic gene expression control.

Neuroimaging Findings in Neurodevelopmental Copy Number Variants: Identifying Molecular Pathways to Convergent Phenotypes.

Genomic copy number variants (CNVs) are associated with a high risk of neurodevelopmental disorders. A growing body of genetic studies suggests that these high-risk genetic variants converge in common molecular pathways and that common pathways also exist across clinically distinct disorders, such as schizophrenia and autism spectrum disorder. A key question is how common molecular mechanisms converge into similar clinical outcomes.

A Community-Driven, Openly Accessible Molecular Pathway Integrating Knowledge on Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) is a highly aggressive malignancy mainly triggered by exposure to asbestos and characterized by complex biology. A significant body of knowledge has been generated over the decades by the research community which has improved our understanding of the disease toward prevention, diagnostic opportunities and new treatments. Omics technologies are opening for additional levels of information and hypotheses.

Overlap of vitamin A and vitamin D target genes with CAKUT-related processes.

Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) are a group of abnormalities affecting the kidneys and their outflow tracts. CAKUT patients display a large clinical variability as well as a complex aetiology. Only 5% to 20% of the cases have a monogenic origin.

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

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.

A resource to explore the discovery of rare diseases and their causative genes.

Here, we describe a dataset with information about monogenic, rare diseases with a known genetic background, supplemented with manually extracted provenance for the disease itself and the discovery of the underlying genetic cause. We assembled a collection of 4166 rare monogenic diseases and linked them to 3163 causative genes, annotated with OMIM and Ensembl identifiers and HGNC symbols. The PubMed identifiers of the scientific publications, which for the first time described the rare diseases, and the publications, which found the genes causing the diseases were added using information from OMIM, PubMed, Wikipedia, whonamedit.

A catalogue of 863 Rett-syndrome-causing MECP2 mutations and lessons learned from data integration.

Rett syndrome (RTT) is a rare neurological disorder mostly caused by a genetic variation in MECP2. Making new MECP2 variants and the related phenotypes available provides data for better understanding of disease mechanisms and faster identification of variants for diagnosis. This is, however, currently hampered by the lack of interoperability between genotype-phenotype databases.

WikiPathways: connecting communities.

WikiPathways (https://www.wikipathways.org) is a biological pathway database known for its collaborative nature and open science approaches.

Integrated analysis of human transcriptome data for Rett syndrome finds a network of involved genes.

Objectives: Rett syndrome (RTT) is a rare disorder causing severe intellectual and physical disability. The cause is a mutation in the gene coding for the methyl-CpG binding protein 2 (MECP2), a multifunctional regulator protein. Purpose of the study was integration and investigation of multiple gene expression profiles in human cells with impaired gene to obtain a robust, data-driven insight in molecular disease mechanisms.

Beyond Pathway Analysis: Identification of Active Subnetworks in Rett Syndrome.

Pathway and network approaches are valuable tools in analysis and interpretation of large complex omics data. Even in the field of rare diseases, like Rett syndrome, omics data are available, and the maximum use of such data requires sophisticated tools for comprehensive analysis and visualization of the results. Pathway analysis with differential gene expression data has proven to be extremely successful in identifying affected processes in disease conditions.

Integration among databases and data sets to support productive nanotechnology: Challenges and recommendations.

Many groups within the broad field of nanoinformatics are already developing data repositories and analytical tools driven by their individual organizational goals. Integrating these data resources across disciplines and with non-nanotechnology resources can support multiple objectives by enabling the reuse of the same information. Integration can also serve as the impetus for novel scientific discoveries by providing the framework to support deeper data analyses.

CyTargetLinker app update: A flexible solution for network extension in Cytoscape.

Here, we present an update of the open-source CyTargetLinker app for Cytoscape ( http://apps.cytoscape.org/apps/cytargetlinker) that introduces new automation features.