whole-exome sequencing

Analysis of reproductive traits associated with lipoprotein(a) deficiency in participants from the Pakistan Genome Resource

The paper analyzes reproductive outcomes in individuals with LPA loss-of-function variants to assess the safety of Lp(a) lowering therapies.

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.

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.

Human and zebrafish data corroborate gene x gene interactions in ameliorating Duchenne muscular dystrophy disease progression

The paper investigates gene-gene interactions in Duchenne muscular dystrophy using human and zebrafish data, finding interaction effects for six gene pairs and rescue of muscle organization in zebrafish for MAN1A1 and ACTN3.

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.

Ultra-rare coding variants in schizophrenia risk genes are associated with longitudinal phenotypic differences across psychotic disorders

This study identifies ultra-rare damaging variants in schizophrenia risk genes and shows they are associated with earlier hospitalizations, greater childhood adversity, and poorer neuropsychological outcomes across psychotic disorders.

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.

Representation learning of somatic missense mutation landscapes across cancer types

This paper introduces MMRL, a framework for learning representations of somatic missense mutations across cancer types, showing improved prognostic discrimination and identification of mutation subtypes.

The genetic, clinical and immune landscape of clonal hematopoiesis across adulthood in the multi-ancestry Mount Sinai Million cohort

This study characterizes clonal hematopoiesis across adulthood and genetic ancestry in a large cohort, finding age-related increases in prevalence, ancestry-specific differences, and associations with immune markers and disease outcomes.

Rare Genetic Mechanisms in Dyggve-Melchior-Clausen Disease

The paper identifies rare genetic variants in DYM causing Dyggve-Melchior-Clausen disease through reanalysis of whole-exome sequencing data from affected individuals.

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.

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.

Exome-based Preconception Carrier Screening for the Mexican Jewish Community; Yields and Implications

This study uses exome sequencing to identify genetic variants in the Mexican Jewish Community, finding higher rates of carrier status and novel alleles compared to standard panels.

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.

Genetic Variants Associated with Placental Abnormalities in Stillbirths

The paper identifies genetic variants associated with placental abnormalities in stillbirths by analyzing exome sequencing data from placental and fetal samples.

vardictcpp: A C++ reimplementation of VarDict variant caller

An AI-assisted C++17 port of VarDictJava gives byte-identical calls on five exome samples while running 3.7-4.8 times faster on one core and needing 8-17 times less memory.

A pan-cancer catalog of mutagenesis at transcription factor binding sites

The paper creates a pan-cancer catalog of mutation patterns at transcription factor binding sites across 15 tissue types, revealing enrichment in nearly one third of TF-binding site pairs.

Latent-Factor Stability Is Not Sufficient: Evaluating SABLE-MO in Simulated and Cancer Multi-Omics Data

The paper evaluates SABLE-MO's performance in identifying shared factors in multi-omics data, finding that stricter retention reduces errors but does not eliminate them.

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.

Clonucopya: An end-to-end workflow bridging tumor clonal architecture and drug prioritization

Clonucopya links tumor clonal architecture to drug prioritization by integrating subclonal inference and drug ranking tools in an end-to-end workflow.

Genomic classification and immune profiling define mucosal melanoma

This study identifies genomic subtypes and immune features of mucosal melanoma, linking CD163+ macrophages to immune resistance and suggesting TIM-3 blockade as a therapeutic target.

Exome-wide rare variant genetic load is associated with cognition, intellectual disability and psychiatric disorders in population-based cohorts

The paper assesses the association between rare variant genetic loads and cognitive traits, intellectual disability, and psychiatric disorders in population-based cohorts.

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.

THE GENETIC LANDSCAPE OF HEREDITARY SPASTIC PARAPLEGIA IN CANADA

This study characterizes the genetic and clinical features of hereditary spastic paraplegia (HSP) in a Canadian cohort, identifying common genetic causes and phenotypic variability.

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.

A versatile set of computational tools for inference of genetic ancestry from human molecular data

The paper introduces RAIDS, a toolset for inferring genetic ancestry from various sequence data, including cancer and low-coverage scenarios.

Positive selection and structural disruption of KCNA5 by mutation in colorectal cancer

The paper identifies KCNA5 mutations under positive selection in colorectal cancer and shows they disrupt channel structure and function, affecting tumor pathways.

Characterisation of Genetically-Derived Patient Clusters Highlights Genetic Heterogeneity of Inflammatory Bowel Disease

The paper uses GenePy scores and clustering to identify genetic clusters in IBD patients, finding NOD2 and NLRP1 as significant drivers with phenotypic associations.

CodonBench: separating gene context, exon position, and variant-specific component in synonymous-variant classification

The paper evaluates models for classifying synonymous variants by separating gene context, exon position, and variant-specific effects, finding that gene identity and position are more predictive than the variant itself.