Biology subjects

Derks, M.

Publications and source records attributed to Derks, M..

5 recordsLinked to original sources

bioRxiv2026

Source of genome-wide deleterious variation in a global cattle cohort

Background Identifying deleterious DNA changes underpins efforts to improve animal health, welfare, and sustainable breeding. In cattle, current variant prioritization focuses on coding changes, uses single annotation types, and gives limited resolution in non-coding sequence. Results We developed BovCADD (bovine Combined Annotation-Dependent Depletion), a nucleotide-level deleteriousness score for substitutions in Bos taurus and Bos indicus, combining evolutionary constraint, sequence context, epigenetic and regulatory annotations, and gene and protein features. A logistic regression model trained on 41.9 million high-frequency derived alleles from about 3,700 cattle, contrasted with context-matched simulated variants, scored all 8.1 billion possible substitutions. BovCADD distinguished known pathogenic variants from background variation, discriminated among variants within the same consequence class, and scored intronic and intergenic sites. Aggregating scores identified genes carrying rare deleterious variation and revealed elevated genetic load at trait-relevant loci and in bottlenecked, intensively selected populations. Conclusions BovCADD provides the first genome-wide, nucleotide-resolution measure of deleteriousness in cattle, extending variant interpretation to non-coding sequences and linking variant-level prioritization to population-level patterns of mutational burden. Precomputed scores for all substitutions are publicly available.

genomics↗

bioRxiv2026

The enhanced multi-tissue atlas of regulatory effects in cattle

Cattle are integral to global food security, yet the molecular architecture of their complex traits remains poorly understood. Here, we present the Cattle Genotype-Tissue Expression (CattleGTEx) Phase 1 resource (https://cattlegtex.farmgtex.org/), a substantial expansion of the pilot study. By leveraging 12,422 RNA-seq profiles across 43 tissues and 82 breeds, we characterized 433,972 primary and 161,428 non-primary regulatory effects spanning seven molecular phenotypes. This high-resolution atlas resolves 75% of GWAS signals for 44 complex traits, significantly addressing the "missing regulation" in livestock. We propose a genetic regulatory model demonstrating how variants across multiple biological layers interact with specific biological contexts to shape phenotypic variation. Furthermore, CattleGTEx elucidates mechanisms underlying adaptive evolution between Bos taurus and Bos indicus, as well as artificial selection in dairy and beef breeds. Finally, by mapping evolutionary constraints on these regulatory effects, we demonstrate the translational value of this resource for prioritizing causal variants in human complex diseases. Together, Phase 1 of CattleGTEx provides a transformative framework for functional genomics, precision breeding, and comparative genetics.

genetics↗

bioRxiv2025

Unmapped reads from whole-genome sequencing data reveal pathogen diversity in European and African cattle breeds

Climate change is impacting the global spread of infectious diseases, altering pathogen distribution and transmission, threatening human and animal health. This study investigates the presence of potential pathogens in blood within unmapped reads obtained from whole-genome sequencing data of various cattle breeds across geographically diverse regions, including South Africa, Uganda, Egypt, Portugal, The Netherlands, and Finland. Unmapped reads were extracted, assembled into contigs, and subjected to taxonomic analysis based on an extensive literature search. The analysis revealed significant geographic variation in pathogen composition, with breeds in the Southern Hemisphere (Uganda, Egypt, and South Africa) showing higher alignment pathogen counts while northern breeds (particularly from Finland) exhibited lower diversity and counts. Portugal, representing a transition zone, exhibited a higher burden of parasites and tick-borne related pathogens which were also prevalent in Southern Hemisphere breeds such as Theileria parva, Anaplasma platys, Theileria orientalis, and Babesia bigemina, which is in line with the known capacity of these breeds to cope with local pathogens. Dutch breeds were found to harbor Escherichia coli O157, a known public health concern. The study provided key insights into emerging disease risks influenced by climate change and livestock management practices. This study highlights the potential for climate-driven variations in disease ecology and transmission, emphasizing the need for integrating genomic and environmental data and is currently the most comprehensive study to date investigating the microbial diversity present in unmapped reads obtained from WGS data of cattle populations. HighlightsO_LIUnmapped sequence reads analysis of blood reveals signatures of disease occurrence over time. C_LIO_LIBlood pathogens prevail in the Southern hemisphere, becoming less evident towards northern regions (i.e. we observed a gradient pattern), with Portugal (and partly the Netherlands) showing intermediate values. C_LIO_LIThe commercial Holstein cattle in the six countries exhibited lower pathogen sequence alignments than their native counterparts (i.e. the Netherlands). C_LI

bioinformatics↗

bioRxiv2024

A generic pipeline for CADD score generation: chickenCADD and turkeyCADD

Combined Annotation Dependent Depletion (CADD) is a machine learning approach used to predict the deleteriousness of genetic variants across a genome. By integrating diverse genomic features, CADD assigns a PHRED-like rank score to each potential variant. Unlike other methods, CADD does not rely on limited datasets of known pathogenic or benign variants but uses larger and less biased training sets. The rapid increase in high-quality genomes and functional annotations across species highlights the need for an automated, non-species-specific pipeline to generate CADD scores. Here, we introduce such a pipeline, facilitating the generation of CADD scores for various species using only a high-quality genome with gene annotation and a multi-species alignment. Additionally, we present updated chickenCADD scores and newly generated turkeyCADD scores, both generated with the pipeline.

genomics↗

bioRxiv2019

A blueprint of seed desiccation sensitivity in the genome of Castanospermum australe

O_LIMost angiosperms produce seeds that are desiccated on dispersal with the ability to retain viability in storage facilities for prolonged periods. However, some species produce desiccation sensitive seeds which rapidly lose viability in storage, precluding ex situ conservation. Current consensus is that desiccation sensitive seeds either lack or do not express mechanisms necessary for the acquisition of desiccation tolerance.\nC_LIO_LIWe sequenced the genome of Castanospermum australe, a legume species producing desiccation sensitive seeds, and characterized its seed developmental physiology and - transcriptomes.\nC_LIO_LIC. australe has a low rate of evolution, likely due to its perennial life-cycle and long generation times. The genome is syntenic with itself, with several orthologs of genes from desiccation tolerant legume seeds, from gamma whole-genome duplication events being retained. Changes in gene expression during development of C. australe seeds, as compared to desiccation tolerant Medicago truncatula seeds, suggest they remain metabolically active, prepared for immediate germination.\nC_LIO_LIOur data indicates that the phenotype of C. australe seeds arose through few changes in specific signalling pathways, precluding or bypassing activation of mechanisms necessary for acquisition of desiccation tolerance. Such changes have been perpetuated as the habitat in which dispersal occurs is favourable for prompt germination.\nC_LI

plant biology↗