407 papers
This study demonstrates that machine learning models trained on cell-free DNA fragmentomics can accurately infer DNase1L3 activity and identify R206C homozygotes, while also revealing that the resulting aberrant fragmentome represents a stable, time-dependent end-state in homozygotes compared to the transient effects observed in wildtype or heterozygote individuals.
By integrating low-frequency genetic variants with serum protein measurements in a large Icelandic cohort, this study reveals that these variants significantly expand the detection of cis-pQTLs, uncovering widespread allelic heterogeneity and distinct biological characteristics—such as enrichment in coding regions and essential pathways—that are often missed when focusing solely on common variants.
This study reports the emergence in Lebanon of a novel, monophyletic ST383 *Klebsiella pneumoniae* lineage that uniquely combines extensive drug resistance (carrying *bla*OXA-48, *bla*NDM-5, and *bla*CTX-M variants) with a full spectrum of hypervirulence factors acquired via ICEKp5, marking a concerning convergence of high-risk traits distinct from previously known local clones.
This study reveals that CTCF plays a dual role in early mammalian development, where its promoter-binding function is essential for initial morphogenesis and gene regulation, while its N-terminal-mediated chromatin looping function becomes critical for sustaining development at later stages.
This study analyzes nearly 4,700 eukaryotic genomes to reveal that genes encoding secreted proteins are consistently enriched in genomic regions characterized by long flanking intergenic sequences and a high density of truncated, fragmented repeats, suggesting an ancient, conserved genomic architecture that drives evolutionary innovation in secreted protein function.
Binary-SPA is a robust, reference-free computational framework that achieves high-accuracy, full-coverage cell type annotation in high-resolution spatial transcriptomics by combining initial marker-based classification with internal anchor-based label transfer, thereby eliminating the need for external single-cell RNA sequencing references.
This study investigates the relative impacts of genetics and heat-related environmental factors on pig whole-blood gene expression, identifying thousands of differentially expressed genes and eQTLs while highlighting specific genetic mechanisms and candidate genes involved in thermoregulation and production traits.
This study demonstrates that the regulatory impact of genetic variants in Massively Parallel Reporter Assays is highly dependent on their position within the DNA sequence, primarily due to context-specific transcription factor binding and structural constraints like Alu element promoter requirements, highlighting the complexity of cis-regulatory grammar.
This study proposes novel cross-validation schemes to enhance genomic selection models for *Miscanthus* breeding, demonstrating that incorporating genotype-by-environment interaction effects significantly improves predictive ability for biomass yield compared to conventional main-effect-only approaches.
This study utilizes multi-omics profiling of postmortem brain tissue to define conserved molecular programs that distinguish vascular, neurodegenerative, and mixed pathologies in late-life dementia, revealing that while individual gene and protein changes vary, pathway-level analyses—particularly involving immune-inflammatory upregulation and mitochondrial downregulation—provide a stable framework for understanding the molecular heterogeneity underlying cognitive impairment.
This study identifies a Denisovan-derived Alu insertion in the OCA2 gene as a key adaptive structural variant that increases skin pigmentation in present-day Melanesian populations by enhancing OCA2 expression and melanocyte activity.
Chronic electronic cigarette exposure accelerates atherosclerosis by driving smooth muscle cells toward a pro-calcifying, chondrogenic phenotype via a GRIN2A-dependent glutamatergic/NMDAR signaling pathway, which can be reversed by inhibiting this specific molecular axis.
This study introduces SAGE, a versatile in vivo AAV-based platform for high-throughput genetic interrogation, which was used to identify Kat8 as essential for alveolar repair and to map transcription factor dependencies that distinguish between reparative and pathological epithelial trajectories in viral lung injury.
This study introduces a streamlined single-library sequencing strategy combining PacBio HiFi and CiFi technologies to generate high-quality, chromosome-scale diploid genomes for prairie and meadow voles, revealing a species-specific duplication of the Avpr1a gene that offers new insights into the genetic basis of pair bonding.
The authors developed in vivo multiomic Perturb-seq, a novel platform that overcomes inefficient nuclear gRNA recovery to enable high-fidelity, single-nucleus multiomic profiling, which they used to uncover cell-type-specific transcriptomic and epigenomic phenotypes of neurodevelopmental disorder risk genes in the developing cortex.
This paper presents a comprehensive, structure-aware framework for interpreting genomic variants in genetic skeletal disorders by integrating experimental and AlphaFold2-derived protein structures with clinical data to reveal structural knowledge gaps, emphasize the importance of multimeric interfaces, and enable mechanistic interpretation of pathogenic and uncertain variants.
This paper proposes a novel R²-based total mediation effect measure and a cross-fitted estimation procedure within a liability framework to address the limitations of existing methods in analyzing high-dimensional mediators for binary outcomes in case-control studies, demonstrating its effectiveness in identifying weak metabolomic mediators of the BMI-coronary heart disease relationship.
This study presents a scalable, cost-effective metagenomic surveillance framework leveraging Brazil's existing rabies monitoring program to detect diverse zoonotic viruses in urban bats, including a novel filovirus, thereby validating a practical One Health model for epidemic preparedness in low- and middle-income countries.
This study demonstrates that refined Feulgen image analysis densitometry (FIAD) offers a low-cost, highly accurate, and reproducible method for measuring genome sizes in ethanol-preserved field samples, achieving precision comparable to whole-genome sequencing and flow cytometry, as validated by the first genome size measurement of the red bald uakari monkey.
This study demonstrates that inferences about a trait's genetic architecture, particularly regarding SNP heritability and the inferred direction of allelic effects, are significantly influenced by study design and cohort representation, with the latter often driven by the skewness of the trait distribution within the specific biobank.