variant effect prediction

SARDINE unlocks EWAS summary statistics for large-scale epigenetic biomarker analysis

SARDINE uses EWAS summary statistics to estimate epigenetic clock-phenotype associations without individual-level data, revealing heterogeneity in biomarker associations with aging and diseases.

Learning Strand-Equivariant Tokenizations of DNA with MirrorDNA

This paper introduces MirrorDNA, a DNA language model with a strand-equivariant tokenizer that improves prediction consistency across DNA strands.

Structural Variant Aware Identity-by-Descent Detection on Pangenome Graphs

GIBD detects IBD segments in pangenome graphs and annotates them with structural variants, outperforming existing methods in accuracy and speed.

memVar: an integrated resource for interpreting human membrane protein variation in molecular and disease contexts

memVar links human membrane protein variants to molecular contexts and disease, revealing enrichment of pathogenic variants in transmembrane regions and interaction sites.

A protein language model for domain, functional site, and variant effect prediction

PALM, a protein language model, predicts domain, functional site, and variant effects with high accuracy using curated sequence data and outperforms existing models in multiple benchmarks.

Transportability of mouse gene knockout models to human complex phenotypes

The paper assesses the transportability of mouse gene knockout models to human complex phenotypes using GPAT framework, finding evidence for 12 phenotypes but limited for others.

A Bias Correction Method for Substructure Estimation with Small Reference Sample Sizes

The paper evaluates how small reference sample sizes affect substructure estimation and proposes bias corrections for improved accuracy.

Decoding Cell-type Specific Gene Regulation with CellReg3D by Integrating DNA Large Language Models and 3D Genome Structure

CellReg3D integrates DNA language models and 3D genome structure to model cell-type-specific gene regulation, achieving state-of-the-art performance in predicting epigenetic marks and gene expression.

MicrobeRT: A Framework and Suite of Fine-tuned Language Models for Genomic Sequences

MicrobeRT is a framework of fine-tuned language models for metagenomic analysis, achieving strong performance in taxonomic classification, antibiotic resistance detection, and pathogenicity assessment.

Polygenic polymorphisms cooperate to drive expansion of HCMV adaptive NK cell and NK-like T cell populations

This study identifies genetic polymorphisms in NKG2C, CD16a, and HLA-E that influence NKG2C expression and ADCC capacity in HCMV-infected individuals.

SeverYX: An ensemble framework for robust variant severity classification

SeverYX is an ensemble framework that classifies genetic variants into severity tiers, achieving high concordance with ClinVar and improving predictive accuracy through threshold optimization and additional predictors.

LRCQ: phenome-wide heritability enrichment of genomic loci from GWAS summary statistics

LRCQ estimates phenome-wide heritability enrichment of genomic loci using GWAS summary statistics, identifying enriched regions and their functional annotations.

Perturbation-induced gene programs map the hidden regulatory architecture of complex diseases

This paper introduces Perturbscape, a framework that uses perturbation-induced gene programs to identify disease-relevant genes and pathways, showing higher heritability informativeness than steady-state approaches.

Neural RNA splicing models rely on reading frame information unavailable to the splicing machinery

The paper shows that neural RNA splicing models rely on reading frame information that the splicing machinery cannot access, leading to errors in predicting poison exons.

Functional Screening of Kv7.5 Channel Variants Associated with Neuronal Dysfunction

This study functionally characterizes Kv7.5 channel variants, identifying gain- and loss-of-function effects and proposing a z-score classification for pathogenicity.

A population-based resource for the prioritization of rare variants of unknown significance in clinical genomics

The paper identifies rare founder variants in a population and develops a platform for variant prioritization, showing that some pathogenic variants may be missed by conventional methods.

A cytotoxicity dataset for data-driven design of ionizable lipid nanoparticles

The paper presents a curated dataset of 1,413 LNP cytotoxicity measurements to examine structure-activity relationships and develop computational models of lipid nanoparticle cytotoxicity.

FastaGuard: FASTA preflight QC for modern bioinformatics pipelines

FastaGuard is a FASTA preflight QC tool that detects structural issues in assemblies and stops pipelines before expensive analysis, with high accuracy in identifying faults.

CNVision: a computational framework for functional interpretation of intragenic copy number variants

CNVision is a computational framework that automates the interpretation of intragenic copy number variants by standardizing input parsing, transcript mapping, and reading-frame classification.

Variant Classification of a Non-Protein Coding Gene: ACMG/AMP Specifications for RMRP from the Clinical Genome Resource Severe Combined Immunodeficiency Disease Variant Curation Expert Panel

This paper adapts ACMG/AMP variant classification criteria for the non-protein-coding gene RMRP, resulting in a framework for classifying variants in cartilage-hair hypoplasia.

Synthetic MPRA perturbation supervision improves variant-effect prediction in sequence-to-function models

This paper improves variant-effect prediction in sequence-to-function models using synthetic MPRA data generated from distilled model predictions.

Unsupervised prioritization of gene-regulatory variants with isolation forests

The paper introduces eQIF, an unsupervised machine-learning method that integrates Enformer predictions to prioritize gene-regulatory variants, showing strong performance in predicting eQTLs and GWAS variants.

Phylogeny-Guided Global-Local Shrinkage for Microbiome Feature Selection

This paper introduces PGL, a Bayesian regression method for microbiome feature selection that uses phylogenetic trees to improve detection of exposure-associated ASVs.

DoAggregate: a pipeline for aggregation testing for rare-variant on a gene and pathway level

DoAggregate performs rare-variant aggregation tests across genes, pathways, and GO terms, providing detailed cohort-level results and visualizations.

Conformation governs cellular behaviors of LRRK2 Parkinson's disease variants

This study identifies 'unlatching' as a common mechanism for Parkinson's disease-associated LRRK2 variants, showing increased membrane localization and decreased S935 phosphorylation.

Cellular context shapes the transcriptomic impact of somatic variants

The paper shows that somatic variants' transcriptomic impact depends on cellular context, not just sequence, using single-cell transcriptomics and new tools.

Leakage-Controlled Benchmarking of Variant Effect Predictors and Development of Gradient-Boosting Consensus Model

The paper benchmarks variant effect predictors using a leakage-controlled dataset and develops a gradient-boosting consensus model that outperforms existing tools.

Beyond a single threshold: calibration of CADD v1.7 and AlphaGenome for ACMG/AMP computational evidence across variant classes, model versions, and reference data

This paper calibrates CADD v1.7 and AlphaGenome AVI for ACMG/AMP computational evidence across variant classes, showing AVI outperforms CADD and highlights the need for class-specific thresholds.

Reference calibration, autozygosity and blood-derived variant interpretation in older adults

This study analyzes genetic variation in older Lebanese adults to distinguish reference sampling biases from true allele frequency differences and genotype expectations.

ClinGen Hemoglobinopathy VCEP ACMG/AMP specifications for HBB and HBA2 variant interpretation in thalassemia

The paper develops and validates disease-specific ACMG/AMP variant interpretation specifications for HBB and HBA2 in thalassemia, providing a standardized framework for globin gene variant classification.