variant effect prediction

Kidzoi Enables Cell-Type-Specific Regulatory Activity and Variant Effect Prediction in Kidney

Kidzoi is a kidney-specific sequence-to-function model that improves variant effect prediction and chromatin accessibility prediction in proximal tubule cells.

The mammalian genome is punctuated by regularly spaced nucleosome islands

The paper trains a deep-learning model to predict nucleosome occupancy from DNA sequence in mouse embryonic stem cells and identifies short DNA motifs that organize nucleosome arrays.

Structure-Informed Stress-Testing of the Standard Numbering Scheme for Class B β-Lactamases Using AlphaFold2

The paper uses AlphaFold2 to model class B β-lactamases without experimental structures, tests the BBL numbering scheme's validity, and identifies structural exceptions.

Significance filtering induces denominator selection bias in local genetic correlation: closed-form characterisation, a gate-aware correction, and an applicability diagnostic

The paper identifies a bias in local genetic correlation estimation due to significance filtering and proposes a correction method with a diagnostic tool.

Agent-optimized GPU polygenic scoring at cohort scale

The paper develops a GPU-accelerated polygenic scoring method using an autonomous coding agent, achieving speedups on synthetic data but showing discrepancies on real data.

Homology-Based Variant-Effect Predictors Break Down on Cytochrome P450 Pharmacogenes

The paper shows homology-based variant-effect predictors fail for CYP enzymes and proposes an improved model that still lacks clinical relevance.

Uncovering Functional Distant Mutations by Ultra-High-Throughput Screening of Dehalogenases

This study uses ultrahigh-throughput screening to identify mutations in dehalogenases that modulate substrate access and binding, revealing distal functional effects on enzyme dynamics.

Functional modelling of human infertility-associated genetic variants using C. elegans and mice

This study uses C. elegans and mouse models to functionally validate infertility-associated genetic variants in MSH4, showing their pathogenic effects on meiotic processes in both sexes.

Rare Germline Variants and Genetic Susceptibility to Pleural Mesothelioma: Moving Beyond DNA Repair

The paper identifies rare pathogenic variants and polygenic risk factors associated with pleural mesothelioma risk and survival.

Applying AlphaGenome Variant Impact for SNV Prioritization

The paper establishes AVI_QUANTILE thresholds for classifying SNVs using ClinVar data and evaluates their performance in variant prioritization and fine-mapping.

Scalable saturation mutagenesis reveals gene regulatory architecture and rare variant effects

The paper introduces Multi-ISM, a scalable framework for saturation mutagenesis that reduces computational cost while maintaining accuracy, and applies it to 5,000 genes to map regulatory elements and rare variant effects.

Plasma proteomics enhances genetic risk prediction and biological understanding of venous thromboembolism

This study integrates plasma proteomics with genetic risk scores to improve VTE prediction and identify potential therapeutic targets.

Byte-exact, format-aware compression for FASTA, FASTQ, BED and VCF files

NYX provides fast, lossless compression for common omics data formats, achieving better compression ratios and speed than existing codecs.

When to Trust Epigenetic Clocks: Avoiding False Positives in Aging Interventions.

This study evaluates epigenetic clocks for aging interventions, finding newer clocks trained on mortality or aging rates are more reliable than those based on chronological age.

A systematic delineation of 3' UTR regulatory elements and their contextual associations

The paper identifies 3'UTR regulatory elements using synthetic inserts and a deep learning model, revealing their effects on gene expression and nuclear-cytoplasmic partitioning, and highlights disease-relevant variants.

SysNDD: A Systematic Database for Neurodevelopmental Disorders

SysNDD is a curated database of gene-disease associations for neurodevelopmental disorders, providing standardized evidence and annotations for 4,275 entities from 4,932 publications.

Systematic screen of PKR reveals genetic variants that broadly evade divergent viral pseudosubstrate inhibitors

This study screens genetic variants of PKR to identify those that resist diverse viral pseudosubstrate inhibitors, finding shared resistance mechanisms across different inhibitors.

Social genetic effects on feed intake in pigs: from feeding visits to total intake

The paper develops a model to quantify social genetic effects on feed intake in pigs by analyzing feeding visit intervals and transforming variance components into aggregated traits.

The prevalence of protein misfolding as a mechanism for hereditary deafness

The paper evaluates computational frameworks to prioritize pathogenic variants in deafness-associated genes, identifying 28,866 VUSs with high pathogenicity probability and improving diagnoses for 12 patients.

vartracker: an end-to-end tool for pathogen longitudinal variant analysis and visualisation

vartracker analyzes and visualizes pathogen variants over time, tracking their evolution and classification across longitudinal datasets.

A moving target: non-stationary selection governs unsupervised prediction of viral fitness

This paper develops an unsupervised pipeline to predict viral fitness using sequence data and finds that protein alignment, not model size, is key for accurate prediction.

BatchVaria: variance-based evaluation of batch correction with provenance tracking

BatchVaria evaluates batch correction methods by comparing variance changes across configurations using TCGA breast cancer RNA-seq data.

Single-Nucleus Multi-Omic Atlas Maps Regulatory Architecture and Non-Coding Variant Effects across Adult Human Tissues

The paper constructs a single-nucleus multi-omic atlas of adult human tissues, identifying regulatory elements and variant effects across 21 tissues.

PathoBERT: A Hybrid Attention-Based Genomic Language Model for Read-Level Bacterial Pathogenicity Prediction

PathoBERT improves bacterial pathogenicity prediction from short reads by combining a DNABERT encoder with attention-based feature extraction, achieving better performance than existing methods.

A novel matrix multiplication framework for modeling genotype-by-environment interaction in genomic prediction

This paper introduces a matrix multiplication framework for genotype-by-environment interaction in genomic prediction, showing improved accuracy over traditional methods.

HipHap: Haplotype Assignment and Confidence Scoring for Diploid Reference Genomes

HipHap improves haplotype assignment and confidence scoring for diploid genomes by aligning reads to each haplotype separately and introducing a quality score.

MaveMD: A functional data resource for genomic medicine

MaveMD provides a clinical interface for MAVE data to classify variants of uncertain significance and improve genetic medicine outcomes.

SCAR: Controlled mutations, ancient DNA damage, and fragmentation of fasta and fastq sequences

SCAR introduces controlled mutations, fragmentation, and damage to sequencing data for benchmarking analyses affected by these factors.

vep-rs: high-throughput Rust variant annotation with population-scale concordance to Ensembl VEP

vep-rs is a Rust reimplementation of Ensembl VEP with high concordance and significantly improved throughput for variant annotation.

Expanding clinical and variant spectrum of CBX1-related syndrome: Report of three novel cases

This paper reports three novel de novo CBX1 variants in patients with developmental delay and describes genotype-phenotype correlations.