Biology subjects

van der Voet, M.

Publications and source records attributed to van der Voet, M..

3 recordsLinked to original sources

bioRxiv2022

Herb-paths, a network and statistical model to explore health-beneficial effects of herbs and herbal constituents

Predictions on bioactivities of herbs and herbal compounds could greatly aid drug development, but require integration of available information on herb and compound effects from various databases. We present Herb-paths, an integrated network connecting information on health-beneficial effects of herbs and herbal constituents. The statistical models included in Herb-paths allow for the calculation of the association strength of herbal (constituents) with health-beneficial effects, for both known and novel effects, and give insight into the major bioactive compounds and molecular mechanisms driving the effects. Herb-paths predictions were tested and validated using a case-study of Panax notoginseng and its derived medicinal extract of Panaxatriol saponins (PTS), used in traditional Chinese medicine to treat stroke and other cardiovascular and cerebrovascular thromboembolic (CCT) disorders. Results showed that Herb-paths predicted known and novel associations between PTS/Notoginseng and CCT phenotypes and diseases, including stroke. Predicted novel associations, such as MoyaMoya disease, are promising putative leads for treatment with PTS/Notoginseng, to be tested in further studies.

bioinformatics↗

bioRxiv2019

From rare Copy Number Variations to biological processes in ADHD

AimAttention-deficit/hyperactivity disorder (ADHD) is a highly heritable psychiatric disorder. The objective of this study was to define ADHD-associated candidate genes, and their associated molecular modules and biological themes, based on the analysis of rare genetic variants.\n\nMethodsWe combined data from 11 published copy number variation (CNV) studies in 6176 individuals with ADHD and 25026 controls and prioritized genes by applying an integrative strategy based on criteria including recurrence in ADHD individuals, absence in controls, complete coverage in copy number gains, and presence in the minimal region common to overlapping CNVs, as well as on protein-protein interactions and information from cross-species genotype-phenotype annotation.\n\nResultsWe localized 2241 eligible genes in the 1532 reported CNVs, of which we classified 432 as high-priority ADHD candidate genes. The high-priority ADHD candidate genes were significantly co-expressed in the brain. A network of 66 genes was supported by ADHD-relevant phenotypes in the cross-species database. In addition, four significantly interconnected protein modules were found among the high-priority ADHD genes. A total of 26 genes were observed across all applied bioinformatic methods. Look-up in the latest genome-wide association study for ADHD showed that among those 26, POLR3C and RBFOX1 were also supported by common genetic variants.\n\nConclusionsIntegration of a stringent filtering procedure in CNV studies with suitable bioinformatics approaches can identify ADHD candidate genes at increased levels of credibility. Our pipeline provides additional insight in the molecular mechanisms underlying ADHD and allows prioritization of genes for functional validation in validated model organisms.

genetics↗

bioRxiv2019

Intellectual Disability-related genes increase ADHD risk and locomotor activity in Drosophila

ObjectiveAttention-Deficit/Hyperactivity Disorder (ADHD) is a common, highly heritable neuropsychiatric disorder. ADHD often co-occurs with Intellectual Disability (ID), and shared overlapping genetics have been suggested. This study aimed to identify novel ADHD genes by investigating whether genes carrying rare mutations linked to ID contribute to ADHD risk through common genetic variants. Validation and characterization of candidates were performed using Drosophila melanogaster.\n\nMethodCommon genetic variants in a diagnostic gene panel of 396 autosomal ID genes were tested for association with ADHD risk, through gene-set and gene-wide analyses, using ADHD meta-analytic data of the Psychiatric Genomics Consortium (n=19,210) for discovery and iPSYCH ADHD data for replication (n=37,076). The significant genes were functionally validated and characterized in Drosophila by assessing locomotor activity and sleep upon knockdown of those genes in brain circuits.\n\nResultsThe ID gene-set was significantly associated with ADHD risk in the discovery and replication data-sets. The three genes most consistently associated were MEF2C, ST3GAL3, and TRAPPC9. Performing functional characterization of the two evolutionary conserved genes in Drosophila melanogaster, we found their knockdown in dopaminergic (dMEF2) and circadian neurons (dTRAPPC9) to result in increased locomotor activity and reduced sleep, concordant with the human phenotype.\n\nConclusionsThis study reveals that a large set of ID-related genes contributes to ADHD risk through effects of common alleles. Utilizing this continuity, we identified TRAPPC9, MEF2C, and ST3GAL3 as novel ADHD candidate genes. Characterization in Drosophila suggests that TRAPPC9 and MEF2C contribute to ADHD-related behavior through distinct neural substrates.

genetics↗