variant effect prediction

Over-representation of sperm-associated deleterious mutations across wild and ex situ cheetah (Acinonyx jubatus) populations

The paper analyzes deleterious mutations in cheetah populations, finding higher inbreeding and sperm-related mutation enrichment in certain populations.

ClinGen Glaucoma Variant Curation Expert Panel recommendations enhance classification of myocilin variants

The paper curates 271 MYOC variants in open-angle glaucoma patients using updated ClinGen guidelines, increasing definitive classifications and highlighting the need for functional evidence.

Rare variants drive high variance in human ancestral fitness at mutation-selection-drift balance

The paper estimates human genetic load variation due to rare and ultra-rare deleterious mutations, showing significant ancestral fitness differences between individuals.

An interpretable omnigenic neural network architecture for the human genome

The paper introduces an interpretable neural network architecture for genomic prediction, outperforming existing methods in disease risk prediction and capturing non-linear genetic interactions.

Variant characterization in the intrinsically disordered human proteome

The paper improves variant effect prediction in intrinsically disordered regions by combining sequence analysis, AlphaFold, and experiments to annotate protein interactions and predict deleterious variants.

Genetic parameters and genome-wide association analysis of service sire effect on litter size and its relationship with boar semen quality in three terminal sire lines

This paper estimates genetic parameters and performs GWAS to analyze service sire effects on litter size and its relationship with semen quality in three terminal sire lines.

Additive and epistatic QTL contribute to the adaptation of the fungus Leptosphaeria maculans to Brassica carinata

The paper identifies seven QTL associated with Leptosphaeria maculans adaptation to Brassica species and finds epistasis contributes to transgressive phenotypes in progeny isolates.

CENO: A Genome-Scale World Model for Evolutionary Sequence Interpretation and Programmable Regulatory Design

CENO is a long-context generative model for genomic sequence understanding and design, showing improved variant prediction and regulatory sequence generation across species.

Variant intolerance scores in cattle

This paper estimates variant intolerance scores for cattle genes and predicts protein domains, finding similar patterns to other species and moderate correlation with human orthologs.

Self-Interaction Nanoparticle Spectroscopy Predicts High-Concentration Viscosity of Therapeutic IgG1 Antibodies

This study evaluates PS-SINS for predicting high-concentration viscosity of IgG1 antibodies, showing strong correlation with viscosity and improved model accuracy when combined with in silico data and DLS.

Reclassification of Genetic Variants in Patients with Hypertrophic Cardiomyopathy from the Sarcomeric Human Cardiomyopathy Registry (SHaRe)

The paper reclassifies genetic variants in HCM patients using a large registry, finding 10% of variants were reclassified, with most VUS unlikely to be causal.

Natural variation in DXR expression is associated with apical hook bending under NaCl stress in Arabidopsis thaliana

Biological versus Technical Reliability of Epigenetic Clocks and Implications for Disease Prognosis and Intervention Response

This study evaluates the technical and biological reliability of 18 epigenetic clocks and shows that technical reliability does not predict biological reliability, which is critical for clinical applications.

A comprehensive map of missense trafficking variants in rhodopsin and their response to pharmacologic correction

The paper presents a high-resolution map of RHO missense variants' trafficking and evaluates pharmacologic correction with YC-001, identifying pathogenic variants and therapeutic potential.

Sequence effects on mutation frequencies investigated in whole-genome sequenced UK Biobank participants

The paper analyzes mutation frequencies in UK Biobank whole-genome sequences, finding that AC25 variants closely match de novo mutations and are influenced by DNA context and transcriptional processes.

Sequence determinants of pathogenicity in glucose-6-phosphatase linked to glycogen storage disease type 1a

The paper uses AlphaMissense and experimental assays to analyze 78 G6PC1 variants, identifying stability and allosteric modulation as key pathogenic mechanisms.

When Less Is Enough: Low-Rank Structure in DNA Sequence-to-Function Models

This paper shows that low-rank approximations of DNA sequence-to-function models can achieve high performance while significantly reducing model size and computational cost.

MetaSplice: pathogenicity prediction and ACMG/AMP evidence for intronic variants outside the canonical splice sites

MetaSplice improves pathogenicity prediction for non-canonical intronic variants by combining splicing predictions with conservation and gene-level constraints, achieving higher accuracy than existing tools.

Enhancing Missense Variant Classification in Predicted Intrinsically Disordered Regions

The paper enhances missense variant classification in intrinsically disordered regions by integrating IDR-specific features with existing predictors, significantly improving PR-AUC scores.

Motif-Centered Analyses Reveal Universal and Tissue-Specific Mutagenic Mechanisms Operating in the Human Body

The paper analyzes somatic mutation profiles in normal human tissues to identify mutagenic mechanisms and their association with age, disease, and environmental exposures.

Complete Mutagenesis of the Genome and Proteome of {Phi}X174

This paper systematically mutagenizes the genome and proteome of PhiX174, revealing that most mutations impair fitness, with protein interaction disruptions being a major cause.

A Reproducible MFASS Benchmark of Splice-Disruption Predictors Reveals a Shared Exon-Interior Blind Spot

The paper benchmarks four splice-disruption predictors using experimental data, finding Pangolin performs best and identifying a shared blind spot in exon interiors.

TMRCA is observable from the branch lengths of a coalescent

The paper develops a model-free estimator for the product of genealogical tree height and scaled mutation rate using site frequency spectra, showing it is unbiased and performs better than tree height averaging in simulations.

Comprehensive Mapping of SGCA Variant Effects Reveals Domain-Specific Constraints Relevant to Sarcoglycanopathies

The paper systematically evaluates SGCA variant effects using saturation mutagenesis to distinguish functional and non-functional variants, revealing domain-specific constraints in sarcoglycanopathies.

FARM: Forecasting Antibiotic Resistance in Mycobacterium tuberculosis using biophysics and machine learning

The paper develops FARM, a framework to predict antibiotic resistance in Mycobacterium tuberculosis by combining biophysical and machine learning features, achieving high accuracy in distinguishing resistance-associated variants.

EXCAVATE-HT: A Bioinformatic Pipeline to Identify Targetable Genomic Variants for Allele-Specific Editing

EXCAVATE-HT identifies targetable genomic variants for allele-specific CRISPR editing by analyzing population data and generating gRNA libraries.

GenVarLoader: An accelerated dataloader for applying deep learning to personalized genomics

GenVarLoader accelerates deep learning applications in personalized genomics by improving data loading speed and compression.

Improving performance of polygenic risk scores for hypertension across two ancestry groups.

This paper compares two Bayesian methods for polygenic risk scores (PRS) for hypertension across two ancestry groups, finding improved performance with updated LD panels and functional annotations, but not equitable results between groups.

An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers

The paper benchmarks missense pathogenicity predictors on cancer drivers and provides a per-gene calibration map to improve their performance in somatic variant interpretation.

TrioNsight: Building a meta-predictor to evaluate the clinical impact of TrioN-like Dbl-homology domain variants

TrioNsight is a meta-predictor that evaluates the clinical impact of TrioN-like Dbl-homology domain variants using structural, evolutionary, and physiochemical features.