David B. Goldstein

Atlas of glomerular disease-specific genetic effects on blood transcriptome

The paper generates disease-specific genetic effect maps on the blood transcriptome for five glomerular diseases using whole genome and transcriptome sequencing data from the CureGN cohort.

Transcription factor binding and individual genetic risk for valproate teratogenicity

The paper investigates how genetic variants affecting transcription factor binding contribute to valproate-induced birth defects and identifies EP300 as a key regulator involved in this process.

RNA methyltransferase SPOUT1/CENP-32 links mitotic spindle organization with the neurodevelopmental disorder SpADMiSS

The paper identifies SPOUT1/CENP-32 as a causative gene for SpADMiSS, linking its dysfunction to mitotic spindle defects and neurodevelopmental disorders.

Investigating the Relationship Between Rare Genetic Variants and Fibrosis in Pediatric Nonalcoholic Fatty Liver Disease

This study examines rare genetic variants in pediatric NAFLD patients with advanced fibrosis but finds no genome-wide significant associations with fibrosis or other histologic features.

A genome-wide mutational constraint map quantified from variation in 76,156 human genomes

Rare-variant depletion in 1kb windows of 76,156 gnomAD genomes, versus feature-adjusted mutation expectations, marks regulatory elements and outperforms seven alternative scores at flagging functional non-coding variants.

Challenges associated with diagnostic exome sequencing in liver diseases

This study evaluates exome sequencing in liver diseases, finding a 5.7% diagnostic rate for monogenic disorders after filtering and manual review.

Inferring compound heterozygosity from large-scale exome sequencing data

The paper develops a method to infer compound heterozygosity from exome sequencing data, achieving high accuracy in phasing rare variants for recessive disease diagnosis.

Strong protective effect of the APOL1 p.N264K variant against G2-associated FSGS and kidney disease

The paper shows the APOL1 p.N264K variant reduces the risk of FSGS and kidney disease in individuals with G2 APOL1 risk alleles.

Aberrant Local Synchrony in Distinct Mouse Models of Epileptic Encephalopathy

The paper develops topological synchrony measures to identify disease-relevant phenotypes in mouse models of epileptic encephalopathies using MEAs.

Rare variant analyses validate known ALS genes in a multi-ethnic population and identifies ANTXR2 as a candidate in PLS

Single Cell transcriptional analysis of ex vivo models of cortical and hippocampal development identifies unique longitudinal trends

The paper uses single-cell transcriptomics to analyze ex vivo models of cortical and hippocampal development, identifying region-specific transcriptomic changes and disease-associated gene expression differences.

Children with Critical Illness Carry Risk Variants Despite Non-Diagnostic Whole Exome Sequencing

This study finds that children with critical illness and non-diagnostic whole exome sequencing may still carry risk variants in genes not previously associated with disease.

Ancestry adjustment improves genome-wide estimates of regional intolerance

This study shows that adjusting for ancestry improves genome-wide estimates of regional intolerance by incorporating demographic history, leading to better variant classification.

Precision genetic cellular models identify therapies protective against endoplasmic reticulum stress

The paper identifies compounds that correct aberrant molecular phenotypes in cellular models of glycosylation defects using a phenotypic screening approach.

Failure to replicate the association of rare loss-of-function variants in type I IFN immunity genes with severe COVID-19

The paper investigates the association of rare loss-of-function variants in type I IFN immunity genes with severe COVID-19 and finds no significant association.

ATAV: a comprehensive platform for population-scale genomic analyses

ATAV provides a scalable platform for population-scale genomic analyses, enabling efficient variant storage, querying, and disease association studies with over 110,000 samples.

Natural selection shapes codon usage in the human genome

The paper shows natural selection optimizes codon usage in the human genome, with dosage-sensitive and cell cycle genes being more intolerant to synonymous variation.

Evaluating potential drug targets through human loss-of-function genetic variation

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.

The mutational constraint spectrum quantified from variation in 141,456 humans

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.

Transcript expression-aware annotation improves rare variant discovery and interpretation

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.

Human loss-of-function variants suggest that partial LRRK2 inhibition is a safe therapeutic strategy for Parkinsons disease

The paper analyzes loss-of-function variants in LRRK2 across large genomic datasets to assess the safety of partial LRRK2 inhibition as a Parkinson's disease therapy.

Characterising the loss-of-function impact of 5’ untranslated region variants in 15,708 individuals

The paper systematically studies uORF variants in 15,708 genomes, showing they are under strong negative selection and contribute to disease.

Landscape of multi-nucleotide variants in 125,748 human exomes and 15,708 genomes

The paper analyzes multi-nucleotide variants (MNVs) in 125,748 exomes and 15,708 genomes, identifying their distribution, mutational origins, and functional implications.

Establishing a transcriptome-based drug discovery paradigm for neurodevelopmental disorders

This paper proposes a transcriptome reversal approach for drug discovery in neurodevelopmental disorders to identify compounds that reverse disease-associated gene-expression signatures.

Neurodevelopmental deficits and cell-type-specific transcriptomic perturbations in a mouse model of HNRNPU haploinsufficiency

This study examines HNRNPU haploinsufficiency in mice, identifying neuroanatomical and transcriptomic changes, and highlights cell-type-specific gene expression dysregulation in excitatory neurons.

The paradoxical effects of K+ channel gain-of-function are mediated by GABAergic neuron hypoexcitability and hyperconnectivity.

The paper investigates how a gain-of-function K+ channel variant causes seizures by reducing inhibitory neuron excitability and increasing network hyperconnectivity.

Enhancer redundancy predicts gene pathogenicity and informs complex disease gene discovery

The paper shows that genes with redundant enhancers are less affected by disruptive non-coding mutations and links enhancer size to disease pathogenicity, suggesting eQTLs may misidentify disease genes.

Enrichment of rare protein truncating variants in amyotrophic lateral sclerosis patients

The paper identifies an enrichment of rare protein-truncating variants in ALS patients, highlighting novel genes like DNAJC7 and known ALS genes such as SOD1, NEK1, and FUS.

Predicting the genetic ancestry of 2.6 million New York City patients using clinical data

This paper predicts genetic ancestry for 2.6 million NYC patients using only clinical data from EHRs, achieving over 80% accuracy for unknown or other ancestries.

Modeling and treating GRIN2A developmental and epileptic encephalopathy in mice

This study models GRIN2A-related DEE in mice, identifies seizure and behavioral abnormalities, and evaluates treatment strategies.