Ben Weisburd

The paper identifies immune cell type-specific gene expression regulated by tandem repeats using multi-omics data from large cohorts.

The Rare Genomes Project provides remote genomic sequencing to rare disease families, achieving a 23.3% diagnostic solve rate and highlighting the role of research in overcoming clinical diagnostic barriers.

The paper analyzes disease-associated tandem repeat loci across diverse populations using long-read data, revealing ancestry-specific variation and complex genotype-phenotype relationships.

This paper benchmarks 7 TR genotyping tools using Nanopore long-read data, finding that no single tool is best across all metrics, and that sequence-level accuracy is crucial for clinical and population studies.

This study evaluates the diagnostic yield of short-read and long-read sequencing in rare diseases, finding limited added value from long-read sequencing despite increased variant discovery.

The paper introduces a data model and dataset for rare disease research, enabling interoperable multi-omic data integration across clinical sites.

The paper introduces a computational model to quantify tandem repeat instability using long-read sequencing data and applies it to identify unstable alleles in 256 HPRC cell lines.

gnomAD v4 (730,947 exomes) brings LOFTEE-2 loss-of-function annotation (0.90 precision, strict mode), missense-aware constraint, and LLM-mined literature evidence combined with constraint to rank disease genes.

The paper identifies novel molecular pathways and biomarkers in LAMA2-RD patients by comparing transcriptomic profiles of those with complete versus partial laminin-211 deficiency.

This study benchmarks RNA-seq tools for diagnostic applications, finding they identify 28 diagnoses from 68 samples but only 9 out of 74 undiagnosed cases.

The paper creates a tandem repeat atlas for 39 inbred mouse strains using long-read sequencing, showing TRs are abundant but differ from human TRs in expansion and transposable element association.

STRchive provides a dynamic resource for interpreting TR variants at disease loci, showing most TR diseases affect children and pathogenic genotypes exist in gnomAD without known disease prevalence.

The paper uses long-read sequencing data to analyze STR variability across 2,645 individuals, identifying disease-associated STR loci with elevated allelic variability and introducing the PLVI metric.

The paper develops and validates SMA Finder, a tool to diagnose spinal muscular atrophy in genome, exome, and panel sequencing data, identifying known and novel cases with high accuracy.

The paper introduces a new TR catalog, TRExplorer v1.0, containing 4.86 million loci, designed for both short-read and long-read analyses and includes variation clusters identified using long-read HiFi data.

The paper constructs TRCompDB, a database of 4.4 million tandem repeat loci across 832 human genomes, revealing mutation rates and dynamics influenced by recombination and duplication context.

The paper evaluates variant prioritization methods for rare disease diagnosis using data from the Rare Genomes Project, finding that top models identify causal variants in most solved families and uncover potential candidates in unsolved ones.

The paper quantifies regional missense mutational intolerance using 730,947 exomes to identify constrained gene regions and improve variant interpretation.

The paper identifies a novel neurodevelopmental disorder caused by de novo deletion of the lncRNA CHASERR, showing its role in regulating CHD2 expression and causing developmental and epileptic encephalopathy.

This study evaluates genome sequencing's diagnostic yield in a cohort of undiagnosed rare disease patients, finding it solves 29.3% of cases with specific variant types not detectable by exome sequencing.

The paper develops a genome-wide truth set for tandem repeat variation using SynDip and evaluates TR genotyping tools, finding ExpansionHunter outperforms others in accuracy and speed.

REViewer visualizes sequencing data around long repeat expansions by reconstructing haplotypes and aligning reads, improving the assessment of repeat genotype calls and detecting interruptions.

The paper investigates the association between STMN2 CA repeats and ALS risk using whole genome sequencing data and finds no significant association.

seqr is a web-based tool for analyzing rare disease genomic data, enabling variant filtering, annotation, and collaboration, with over 10,000 families analyzed and 300 novel disease genes discovered.

The paper evaluates penetrance and variable expressivity of monogenic metabolic conditions using exome data from 77,184 individuals, finding that monogenic variants have larger effect sizes than polygenic scores but low penetrance.

This study evaluates genome sequencing as a single diagnostic approach for fetal structural anomalies, showing it detects nearly all variants from standard tests and provides higher diagnostic yield than individual tests.

The paper compares structural variant detection using short-read and long-read sequencing in three trios, showing lrWGS finds more SVs but srWGS has high concordance in non-repetitive regions.

The paper evaluates potential drug targets using loss-of-function genetic variants from gnomAD, highlighting the importance of deep curation and targeted recall studies for drug discovery.

From 125,748 exomes and 15,708 genomes, 443,769 high-confidence predicted loss-of-function variants yield LOEUF, a continuous gene intolerance score tracking mouse lethality, cell essentiality, and disease associations.

The paper develops an expression-based annotation metric to improve rare variant interpretation by filtering false-positive loss-of-function variants and identifying pathogenic variants in highly expressed exons.