variant effect prediction

HERCULES: a deep-learning framework for RNA-binding region localization and mutation-effect prediction

HERCULES predicts RNA-binding regions and mutation effects using a deep-learning framework combining language models and physicochemical descriptors.

Variant effect predictors are shaping the ClinVar classifications used to train and evaluate them

The paper shows that variant effect predictors influence ClinVar classifications, creating circularity in variant classification and prediction.

MPFIL: Multi-Level Protein Feature Integration for Predicting Mutation-Induced Protein-Protein Binding Affinity Changes

MPFIL predicts mutation-induced changes in protein-protein binding affinity by integrating structural and sequential features across multiple levels.

KCNH1 variants associated with neurodevelopmental disorders exhibit prominent gain-of-function

The paper investigates functional properties of KCNH1 variants linked to neurodevelopmental disorders, finding most exhibit gain-of-function characteristics.

Robustness of the inference of the distribution of fitness effects to selective sweeps

This study evaluates how selective sweeps affect DFE inference using fitdadi, finding that performance declines at low recombination rates and with unfolded SFS, but remains largely unbiased with a flexible demographic model.

Utilizing a Variant Prioritization Approach to Explore Genetic Variants in Cervical Cancer Cases among Malawian Women

This study identifies genetic variants associated with cervical cancer in Malawian women using whole genome sequencing and variant prioritization.

A Pipeline for Predicting Variant Associations with Complex Disorders via Functional Annotations

The paper introduces a pipeline to create curated, balanced variant-trait association datasets for complex disorders using GWAS and functional annotations.

AlphaGenome informed machine learning for pathogenicity prediction of germline mutations

AGVarPred is a gradient-boosted classifier that improves pathogenicity prediction of germline variants by integrating AlphaGenome features, outperforming existing models across SNVs and indels.

Evaluating anonymized genome re-identification using polygenic predictions and its implications for data privacy

This paper evaluates the feasibility of re-identifying individuals using polygenic predictions and finds that real-world effectiveness is limited due to low priors and poor sensitivity for sensitive genotypes.

Evaluating the added value of sequence models in noncoding RNA assays: a baseline-aware framework

The paper evaluates sequence models in noncoding RNA assays by comparing model increments against baselines and highlights the importance of baseline content and regularization.

Functional Validation of Known BEST1 Variants Using a Robust Halide-Sensitive YFP Quenching Assay

The paper develops a halide-sensitive YFP quenching assay to functionally validate BEST1 variants and distinguish loss-of-function from gain-of-function mutations.

A robust mutation spectrum analysis framework for high-depth error-corrected sequencing data

The paper introduces a statistical framework to analyze mutation spectra in error-corrected sequencing data, showing it maintains Type I error control and greater power than existing methods.

ONT-LibQC: rapid quality control of chromatin assay libraries using shallow nanopore sequencing

ONT-LibQC uses shallow nanopore sequencing to rapidly assess chromatin assay library quality before deep sequencing, showing consistent results with Illumina sequencing.

Calibration of AlphaGenome Variant Impact and SpliceAI2 scores as PP3/BP4 evidence for missense, non-coding, and synonymous variants

The paper calibrates AlphaGenome Variant Impact (AVI) and SpliceAI2 scores for variant classification, showing their performance across different variant classes and comparison methods.

A heat-assisted ttLbCas12a workflow incorporating crRNA 3'-tailing enables efficient multiplex biallelic genome editing in hybrid poplar

Genotypic evidence of vector-mediated selection on Plasmodium falciparum in infected field-collected Anopheles mosquitoes

The paper analyzes parasite genotypes in sympatric mosquito species to show divergent selection on Plasmodium falciparum mediated by different vectors.

2C-RT Quantifies Genome-Wide DNA Replication Perturbations and Redefines RIF1-CDC7 Regulation of Replication Timing

Sorting S-phase cells by Cyclin A2 rather than DNA content exposes a uniform genome-wide delay after CDC7 inhibition and a broad replication timing advance in RIF1 knockout.

Age-driven miR-29 trades youthful plasticity for epigenetic fidelity

This study identifies miR-29 as a key regulator of age-related epigenetic changes, showing it promotes fidelity but reduces plasticity in methylome maintenance and adaptation.

Functional and acid-stability constraints on the Junin virus glycoprotein complex

This study uses deep mutational scanning to analyze how amino-acid mutations affect the pH stability and cell entry function of the Junin virus glycoprotein complex.

Exploring the role of local sequence context on patterns of germline mutation

The paper maps how local sequence context influences germline mutation rates using 1000 Genomes Project data, showing non-monotonic decay and higher-order interactions.

BUDDY: An interactive web platform to accelerate the functional modeling of human missense variants using Saccharomyces cerevisiae orthologs

BUDDY is a web platform that streamlines the functional modeling of human missense variants using yeast orthologs, reducing bioinformatic preparation time and enabling non-experts to design experiments.

Computational Profiling and Pathogenicity Assessment of VHL Missense Mutations

This study assesses the pathogenicity of VHL missense mutations using AlphaMissense, protein stability simulations, and molecular dynamics to identify critical regions and mutation effects.

EG-BINN: Parameter-Efficient Ensembling of Gated Biologically Informed Neural Networks for Epigenetic Age Estimation

EG-BINN improves epigenetic age estimation by combining parameter-efficient ensembling of biologically informed neural networks with sample-specific gating, achieving lower error rates than existing methods.

Population-scale drug target and variant prioritization with Varformer

Varformer prioritizes drug targets and variants by integrating variant and gene features using a transformer model, achieving high precision across diverse benchmarks.

DEEP: Extracting Latent Energetic Landscapes from Protein Structure Predictors

The paper introduces DEEP-Boltz, a framework that extracts energetic potentials from protein structure predictors, outperforming existing methods in predicting mutation-induced stability changes.

Robust Identification of Drug Mechanism of Action Associated Genes Across Heterogeneous Drug Treated Datasets

This paper introduces ConcuRx, a statistical framework that improves gene prioritization across heterogeneous CRISPR drug-response datasets by modeling between-study variability, leading to better identification of MOA-associated genes.

Delocalized DNA holes imprint mutation position in mismatch-repair-deficient cancers

The paper identifies a specific mutation pattern in mismatch-repair-deficient cancers linked to DNA hole delocalization and oxidation, showing enrichment at 5' guanines and depletion at 3' guanines.

Genome-scale base editing reveals the functional effects of variants in yeast

This study uses genome-scale CRISPR base editing in yeast to assess the functional effects of 308,461 variants, identifying 18,009 with significant growth impacts.

hvantk: an agentic multi-omics framework for variant annotation and analysis

hvantk is a framework for variant annotation and analysis that integrates multi-omic data, improving the recovery of disease genes in case-control cohorts.

A genomic foundation model for interpreting human genetic diversity

The paper introduces hEVO, a genomic foundation model trained on human haplotype sequences, achieving top performance in variant interpretation and functional annotation across multiple benchmarks.