Eleanor G. Seaby

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.

This paper identifies loss-of-function variants in ZFHX3 as a cause of syndromic intellectual disability and describes its role in chromatin remodeling and DNA methylation.

GenePy identifies potential missed biallelic diagnoses in the 100KGP by scoring variants and analyzing phenotypic overlaps, finding 14% of undiagnosed participants may have a missed diagnosis.

The paper identifies de novo monoallelic DDX17 variants in 11 patients with neurodevelopmental disorders and shows DDX17 dysfunction causes neuronal migration and axon outgrowth defects in multiple models.

This paper presents a framework to reduce false positives in predicted loss-of-function variants by analyzing LoF evasion mechanisms and adjusting ACMG/AMP guidelines.

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 compares a panel-agnostic variant filtering approach (HiPPo) with a gene panel-based strategy in exome and genome data from NHS patients, finding HiPPo identifies more diagnostic variants with fewer assessments.

The paper introduces DeNovoLOEUF, a method to identify diagnostic variants in genome sequencing data, achieving 96% positive predictive value and uncovering 39 missed diagnoses in the 100,000 Genomes Project.

The paper identifies six rare de novo missense variants in WDR5 associated with neurodevelopmental disorders and highlights their impact on COMPASS family protein interactions.

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.

This study identifies and characterizes 11 cases of TET3 deficiency, a new Mendelian disorder of DNA demethylation, associated with intellectual disability and developmental delays.