Dib, M.-J. | bioRxiv Science

bioRxiv2026

drugMR: A multi-omics pipeline for genetically anchored drug-target discovery

Motivation: Genetically supported drug targets are an estimated 2.6 times more likely to succeed clinically, yet a disease association alone does not show which protein to target, in which direction, or what other effects may follow. This currently requires chaining separate tools. Results: drugMR is a Nextflow pipeline that, from GWAS and pQTL summary statistics, runs cis-Mendelian randomisation, colocalisation, SMR-HEIDI with bulk and/or single-cell QTLs, three-trait colocalisation and a phenome-wide screen for adverse effects and repurposing. Datasets are added through a manifest, every step runs in containers on a laptop, cluster or cloud, and results are explored in a dashboard. Applied to schizophrenia with brain pQTLs, drugMR tested 2,019 proteins in 4 h 19 min and prioritised 58 proteogenomic targets, 22 with multi-omic support; 4 had potential adverse effects. Availability and implementation: drugMR: https://github.com/guillermocomesanacimadevila/drugMR; documentation: https://guillermocomesanacimadevila.github.io/drugMR/. Demo data: https://doi.org/10.5281/zenodo.22917384.

bioinformatics↗

bioRxiv2024

Three-dimensional aortic geometry: clinical correlates, prognostic value and genetic architecture

BackgroundAortic structure impacts cardiovascular health through multiple mechanisms. Aortic structural degeneration occurs with aging, increasing left ventricular afterload and promoting increased arterial pulsatility and target organ damage. Despite the impact of aortic structure on cardiovascular health, three-dimensional (3D) aortic geometry has not been comprehensively characterized in large populations. MethodsWe segmented the complete thoracic aorta using a deep learning architecture and used morphological image operations to extract multiple aortic geometric phenotypes (AGPs, including diameter, length, curvature, and tortuosity) across various subsegments of the thoracic aorta. We deployed our segmentation approach on imaging scans from 54,241 participants in the UK Biobank and 8,456 participants in the Penn Medicine Biobank. ConclusionOur method provides a fully automated approach towards quantifying the three-dimensional structural parameters of the aorta. This approach expands the available phenotypes in two large representative biobanks and will allow large-scale studies to elucidate the biology and clinical consequences of aortic degeneration related to aging and disease states.

genomics↗