Transmission ratio distortion has been demonstrated in model organisms but is understudied in humans. We conduct single- and multi-locus transmission disequilibrium tests to detect transmission ratio distortion in up to 43,829 parent–offspring trios from the Norwegian Mother, Father and Child Cohort Study. We find little evidence for moderate to high levels of transmission ratio distortion at common variants. However, our multi-locus analyses implicate genes involved in meiosis, fertility, and prenatal development.
Microbial communities contain diverse organisms, including multiple coexisting strains of the same species that display phenotypic differences influencing pathogenicity and host interactions. Detecting strains is challenging because of computational demands and their low abundance in metagenomes. We present UniqSketch, an open-source toolkit for identifying target strains across species within a single metagenome. It tracks specific microbial signatures or contaminants even in complex, multi-species samples. UniqSketch uses unique genomic fingerprints and a compact Bloom filter for efficient computation and accurate abundance estimation. Results show improved precision and accuracy over existing tools, with reliable performance at sequencing coverage as low as 0.1×.
Foundation models have advanced single-cell omics analysis but often remain too complex for practical use. We present CellPatch, a lightweight foundation model combining cross-attention with heuristic gene patching to reduce computational complexity during pretraining and fine-tuning while enabling inspection of gene-attention patterns. Across single-cell RNA-sequencing datasets spanning multiple organs and tissue states, CellPatch achieves state-of-the-art performance on diverse prediction tasks. Its modular design supports linear, adapter-based and task-specific architectures, enabling CellPatch to be adapted to diverse biological tasks.
Geographical imbalance in extremophile plant genomics has left the Mongolian Plateau underexplored. Prunus pedunculata, a desert shrub endemic to this arid region, provides an ideal system for understanding woody plant adaptation to extreme drought, yet its genomic architecture remains unknown. Here we present a telomere-to-telomere genome assembly for P. pedunculata, a dodecaploid (2n = 12 × = 96) with the highest ploidy level among sequenced woody perennials. Its 1.38 Gb genome is resolved into 48 chromosomes, and telomeric repeats are detected in each. Evolutionary analysis confirms an autopolyploid origin with > 80
Natural populations are rich reservoirs of genetic variation, and incorporating this diversity into functional genomic screens can reveal the genetic and phylogenetic determinants underlying trait differences. Genetic barcoding is a powerful tool for yeast functional genomics, enabling scalable fitness profiling and high-throughput gene-trait interaction mapping. Nevertheless, few barcoded libraries capture the natural diversity of Saccharomyces cerevisiae. Here, we introduce BarMix, a novel barcoded library of diverse S. cerevisiae strains designed and validated for high-throughput fitness profiling. Using CRISPR-Cas9, we integrate distinct markerless genetic barcodes into the genomes of 262 strains representing multiple phylogenetic clades of wild, domesticated, and admixed origins. To evaluate its utility for genotype–phenotype mapping, we quantitatively profile the pooled library by barcode-sequencing against 33 small-molecule compounds with diverse bioactivities and identify 281 chemogenomic interactions through genome-wide association analysis. Chemical fitness signatures differ between domesticated and wild clades, particularly under stresses affecting ergosterol biosynthesis, DNA alkylation, microtubule depolymerisation, TORC1 inactivation, and membrane permeability. We validate seven associated alleles through allele-swap experiments, including variants in genes that modulate multidrug export (Yrr1), tRNA-specificity (ArgRS), and small-molecule methylation (Crg1). Several alleles display variable penetrance across strains, suggesting a complex genetic basis for trait variation. Importantly, including admixture into the genome-wide association design enhances variant detection in S. cerevisiae. These results establish BarMix as a powerful platform for genotype–phenotype discovery with diverse applications in functional genomics and biotechnology, and highlight the value of incorporating natural variation into model-systems biology.
