variant effect prediction

Functional architecture of rare protein coding variation across 786,871 exomes

The paper introduces KASM to integrate functional annotations and estimate heritability of rare protein coding variants across 786,871 exomes, finding higher heritability than previous estimates.

Rare variant burden complements polygenic risk in breast cancer and is associated with earlier diagnosis

This study shows that rare variant burden adds information beyond polygenic risk scores for breast cancer and is more strongly associated with earlier diagnosis.

S4-Oligo: optimizing polygenic score methods for clinical deployment

This paper introduces S4-Oligo, an optimized polygenic score method for clinical use, which matches or exceeds existing models' accuracy while using fewer SNPs.

Local population genetic structure of Andrena flavipes (Hymenoptera, Andrenidae), a nest-philopatric communal mining bee, reveals isolation-by-distance and high inbreeding

The paper assesses genetic structure and inbreeding in Andrena flavipes bees using SNPs, finding isolation-by-distance and high inbreeding despite high genetic variation.

Decoding pseudoexon activation by deep intronic variants using a high-throughput minigene assay in the NF1 gene

The paper develops a high-throughput minigene assay to identify pseudoexon-activating variants in the NF1 gene and benchmarks splicing prediction tools.

Accurate repeat expansion genotyping from whole-genome and real-time targeted nanopore sequencing with Mahi-mahi

Mahi-mahi accurately genotypes repeat expansions from nanopore sequencing data, matching orthogonal methods and identifying pathogenic alleles.

Predicting cell-state-specific gene regulation from DNA across species

Bolero predicts cell-state-specific gene regulation from DNA across species by integrating cell-state embeddings and biological variables.

NEIL2 regulates RNA polymerase II dynamics to suppress transcription replication conflicts in pancreatic cancer

This study identifies NEIL2 as a regulator of RNA polymerase II dynamics that suppresses transcription replication conflicts in pancreatic cancer cells.

Accounting for gene action improves the accuracy of polygenic scores for some complex traits

This study introduces PGSa,d, a polygenic scoring framework that incorporates both additive and dominance effects, showing improved accuracy for traits with significant dominance contributions.

The m6A motif is an anti-3' splice site

The paper shows that the m6A writer spares canonical 3' splice sites from methylation, allowing efficient splicing despite cotranscriptional methylation.

Distinct activation mechanisms underlie ligand efficacy at a GPCR

This study uses deep mutational pharmacology to show how different residues in the -opioid receptor determine the efficacy of opioids by shaping distinct activation mechanisms.

DeepD enables efficient genome modeling and controllable long-context sequence generation across domains of life

DeepD is a genome foundation model that enables accurate sequence-to-function prediction and controllable genome-scale sequence generation across domains of life.

MetaDome 2027: a comprehensively updated resource for aggregating missense variant evidence across homologous human protein domains

MetaDome now supports GRCh38 alongside GRCh37, adds coordinate lookup, and identifies 52,463 GRCh38 ClinVar missense variants of uncertain significance with uncontradicted pathogenic evidence at homologous Pfam-domain positions.

Benchmarking the AlphaGenome Variant Impact score against SpliceAI on post-release ClinVar classifications and experimental splicing assays

This paper benchmarks the AlphaGenome Variant Impact score against SpliceAI on post-release ClinVar classifications and experimental splicing assays, finding AVI performs well but not outperforms splicing predictors on AUROC.

Capturing domain-level detail of molecular interactions in the IMEx Consortium binding domain data set

The paper presents a manually curated dataset of protein binding domains, linking them to molecular interactions and genomic variations for benchmarking and disease mechanism studies.

Analysis of single nucleotide substitution in CYP21A2 gene using Alphagenome

The paper analyzes single nucleotide substitutions in the CYP21A2 gene using AlphaGenome to connect clinical annotations, population data, splicing predictions, and enzyme function.

Improved Scalar Deregression of Estimated Breeding Values

The paper introduces an improved method for scalar deregression of estimated breeding values by incorporating inbreeding coefficients and prediction error covariance matrices, resulting in unbiased deregressed values and reliable filtering of uninformative candidates.

Global signatures of Ribonucleotide Excision Repair deficiency and its therapeutic vulnerabilities

This study identifies RER deficiency as a new DNA repair defect in cancer, detectable through mutational signatures and linked to therapeutic vulnerabilities.

Pre-binning correction of chimeric contigs reduces reference-discordant gene annotations in near-complete metagenome-assembled genomes

The paper introduces DeepMM, a deep learning method to correct chimeric contigs in MAGs, improving gene annotation accuracy and reducing reference-discordant genes and virulence-factor calls.

MAP3K7 Loss of Function Causes Dilated Cardiomyopathy

This paper shows that loss-of-function variants in MAP3K7 cause dilated cardiomyopathy (DCM), both as part of syndromic disease and as apparently isolated DCM.

Computational Prediction of Recombinant Expression Efficiency for Industrial Enzymes: An Integrated Co-Translational Sequence Analysis Platform

The paper presents a computational platform to predict recombinant expression efficiency of industrial enzymes by analyzing sequence features and co-translational processes, showing preliminary validation on solubility and other metrics.

Learning Dynamic Protein Representations at Scale with Distograms

Adding Boltz2 distogram edges and features to protein and RNA graph networks beats MD-correlation graphs on binding tasks and improves stability, interaction and RNA predictions without simulation.

Joint Variable Selection for Omic Biomarkers in Time-to-Event Data

The paper introduces vampW, a Bayesian method for joint variable selection in omic biomarkers and time-to-event data, showing reduced false discoveries and improved prediction.

Decoding super-enhancer regulatory grammar and pathogenic gain-of-function variants directly from DNA sequence

This paper introduces Borzoi-SE, a deep learning framework that identifies super-enhancers and detects pathogenic variants directly from DNA sequence across multiple human cell lineages.

DNA-LLM2Vec: Architecture-Aware Task-Conditioned Adaptation of Decoder DNA Foundation Models

DNA-LLM2Vec adapts decoder DNA models to bidirectional context for genomic tasks, improving performance on extended-context tasks but varying by task and backbone.

A benign control-calibrated multiparametric functional assay supports CACNA1A variant assessment

This paper develops a calibrated functional assay to assess CACNA1A variants, showing it can accurately classify pathogenic and benign variants with high specificity and sensitivity.

IVA, a locally deployable Intelligent Variant Analyser based on a small language model for complete case-level and trio-based genomic interpretation.

IVA uses a small language model to perform local genomic variant interpretation, achieving high sensitivity but lower precision in identifying pathogenic variants.

Using Polycistronic gRNAs and a tRNA Cleavage System in CRISPR-Based Genome Editing of Toxoplasma gondii

This paper improves CRISPR-based genome editing in Toxoplasma gondii by optimizing gRNA expression and introducing a tRNA-based polycistronic system for multiplexed editing.

Investigating the pathogenicity of missense spliceogenic variants using whole-genome sequencing, RNA-sequencing, and proteomics data from population and clinical research cohorts

The paper investigates missense spliceogenic variants (MSVs) using genomic and proteomic data, finding they are common and can cause disease through splicing disruption, often missed by protein-centric tools.

A national ecosystem for long-read genome sequencing: Integrating population genomics and rare disease diagnostics in Sweden

This paper evaluates the clinical use of long-read genome sequencing in Sweden, showing it provides molecular diagnoses and reduces diagnostic costs.