bioRxiv Science⌕ Search

Biology subjects

Masiero, M.

Publications and source records attributed to Masiero, M..

2 recordsLinked to original sources

NPmatch: Latent Batch Effects Correction of Omics data by Nearest-Pair Matching

MotivationBatch effects (BEs) are a predominant source of noise in omics data and often mask real biological signals. BEs remain common in existing datasets. Current methods for BE correction mostly rely on specific assumptions or complex models, and may not detect and adjust BEs adequately, impacting downstream analysis and discovery power. To address these challenges we developed NPmatch, a nearest-neighbor matching-based method that adjusts BEs satisfactorily and outperforms current methods in a wide range of datasets. ResultsWe assessed distinct metrics and graphical readouts, and compared our method to commonly used BE correction methods. NPmatch demonstrates overall superior performance in correcting for BEs while preserving biological differences than existing methods. Altogether, our method proves to be a valuable BE correction approach to maximize discovery in biomedical research, with applicability in clinical research where latent BEs are often dominant. Data availability and implementationNPmatch is freely available on Github (https://github.com/bigomics/NPmatch) and on Omics Playground (https://bigomics.ch/omics-playground). The datasets underlying this article are the following: GSE120099, GSE82177, GSE162760, GSE171343, GSE153380, GSE163214, GSE182440, GSE163857, GSE117970, GSE173078, GSE10846. All these datasets are publicly available and can be freely accessed on the Gene Expression Omnibus (GEO) repository.

bioinformatics↗

Zebrafish larvae as a model system for systematic characterization of drugs and genes in dyslipidemia and atherosclerosis

BackgroundHundreds of loci have been robustly associated with circulating lipids, atherosclerosis and coronary artery disease; but for most loci the causal genes and mechanisms remain uncharacterized.\n\nMethodsWe developed a semi-automated experimental pipeline for systematic, quantitative, large-scale characterization of mechanisms, drugs and genes associated with dyslipidemia and atherosclerosis in a zebrafish model system. We validated our pipeline using a dietary (n>2000), drug treatment (n>1000), and genetic intervention (n=384), and used it to characterize three candidate genes in a GWAS-identified pleiotropic locus on chr 19p13.11 (n>500).\n\nResultsOur results show that five days of overfeeding and cholesterol supplementation had independent pro-atherogenic effects, which could be diminished by concomitant treatment with atorvastatin and ezetimibe. CRISPR-Cas9-induced mutations in orthologues of proof-of-concept genes resulted in higher LDL cholesterol levels (apoea), and more early stage atherosclerosis (apobb.1). Finally, our pipeline helped identify putative causal genes for circulating lipids and early-stage atherosclerosis (LPAR2 and GATAD2A).\n\nConclusionsIn summary, our pipeline facilitates systematic, in vivo characterization of drugs and candidate genes to increase our understanding of disease etiology, and can likely help identify novel targets for therapeutic intervention.

genomics↗