Jonathan Adam Bernstein

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.

The paper identifies domain-specific phenotypic effects of MACF1 variants outside the GAR domain, revealing broader neurodevelopmental and craniofacial anomalies.

The paper identifies novel AXIN2 variants causing expanded phenotypes in humans and validates their pathogenicity using human, mouse, and fly models.

METAFORA calls depth-aware, covariate-adjusted methylation outlier regions from PacBio and Nanopore long reads; in 551 rare-disease genomes, outliers tracked structural variants, repeat expansions, and imprinting defects.

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

The paper identifies biallelic variants in RNU2-2 as a common cause of recessive neurodevelopmental disorders, showing higher prevalence than the dominant form in England.

The paper introduces the Intolerome Database, a curated resource of genes essential for human viability, to help prioritize genomic variants in cases of stillbirth, pregnancy loss, and neonatal death.

The paper identifies genetic variants in 30 families with unexplained euploid pregnancy loss, finding monogenic causes in 25% of cases and expanding understanding of early human lethality.

The paper identifies individuals with minor spliceopathies by analyzing transcriptome-wide splicing outliers in RNA-seq data from rare disease cohorts.

The paper compares neurobehavioral profiles of Smith-Kingsmore Syndrome and PTEN Hamartoma Tumor Syndrome, identifying distinct features and diagnostic markers.

The paper identifies biallelic variants in RNU4-2 causing a recessive neurodevelopmental syndrome with distinct white matter changes, expanding the known genotypic and phenotypic spectrum of RNU4-2-related disorders.

The paper presents a joint genomic analysis of UDN patients using whole genome sequencing and new statistical methods to prioritize disease genes, revealing new disease associations and releasing a software tool for cohort analysis.

An LLM agent with a literature-mined environment of 150 tools, 105 packages and 59 databases plans in code, matching reported human accuracy on database and sequence question answering.

The paper integrates long-read sequencing and gene expression to prioritize functional structural variants and tandem repeats in rare disease patients, identifying potential causal variants in a neurodevelopmental disorder.

This study identifies de novo KDM2A variants as a cause of a syndromic neurodevelopmental disorder with specific clinical features and functional consequences.

Mostly de novo variants in an 18 bp constrained region of U4 snRNA gene RNU4-2 cause a syndromic neurodevelopmental disorder, estimated to explain 0.41% of cases.

This study examines how different genome builds affect RNA-seq results in rare disease samples and recommends cross-referencing with a database of build-dependent genes for more accurate transcriptomics analysis.

The paper uses hiPS cell-derived cortical organoids to study how genetic mutations in ASD converge on shared transcriptional changes during development.

The paper applies complete long read sequencing to undiagnosed patients, identifying a 16kb intragenic duplication in EHMT1 causing Kleefstra syndrome.

This study identifies molecular differences between PMS patients with small and large deletions, showing reduced cytotoxic cell signatures and sphingolipid metabolism in large deletions.

This study identifies DPP9 deficiency as a Mendelian disorder causing inflammasome hyperactivity, which can be rescued by reducing NLRP1/IL-1 signaling in mice.

MonoMiner identifies monogenic disease patients with confirmed molecular diagnoses from clinical notes, achieving high precision and recall in a large hospital system.

This paper develops a method to generate neuronal cells from adult fibroblasts and uses it to study gene expression and epigenetic changes in 22q11.2 deletion syndrome.

InpherNet improves disease gene hypothesis generation by leveraging gene network neighbors, achieving higher accuracy than existing methods in prioritizing causative genes.

The paper identifies de novo PRKAR1B variants in six individuals with neurodevelopmental disorder, autism, apraxia, and reduced pain sensitivity.

This study examines the transcriptome and epigenome effects of the 15q13.3 microdeletion in human induced neurons, identifying gene expression and pathway changes linked to neuropsychiatric disorders.

AMELIE 3 automatically reanalyzes undiagnosed Mendelian disease patients using new literature, achieving 80% diagnostic yield with 0.5-1 alerts per patient per year.

AMELIE 2 improves Mendelian disorder diagnosis by matching patient phenotypes and genotypes to primary literature, achieving high accuracy and efficiency.

The paper identifies de novo variants in EIF2AK1 and EIF2AK2 associated with neurodevelopmental disorders and leukoencephalopathy, showing similar pathogenic mechanisms to CACH/VWM.

The paper identifies a recurrent start codon mutation in UGP2 causing a severe epileptic encephalopathy, showing that isoform-specific expression loss of an essential gene can lead to disease.