Samantha J. Bryen

Impact of Rare and Common Genetic Variation on Cell Type-Specific Gene Expression

Single-cell eQTL mapping in 5.4 million PBMCs from 1,925 individuals with matched WGS finds common-variant eQTLs for 83% and rare-variant signals for 47% of 21,404 genes.

SECISBP2 Deficiency Causes a Lethal Perinatal Cardiomyopathy

This study identifies a homozygous SECISBP2 variant causing lethal perinatal cardiomyopathy through loss of selenoprotein function, including GPX4, and suggests a ferroptosis mechanism.

Proteomics Uncovers Cryptic JPH2 Loss in Paediatric Dilated Cardiomyopathy

This study uses proteomics to identify a cryptic JPH2 loss-of-function in a paediatric DCM patient, revealing a novel mechanism of recessive disease.

The Evidence Aggregator: AI reasoning applied to rare disease diagnostics

The Evidence Aggregator (EvAgg) uses generative AI to streamline rare disease diagnostics by extracting and summarizing genetic variant and clinical information from literature, improving efficiency and accuracy.

Scalable automated reanalysis of genomic data in research and clinical rare disease cohorts

The paper develops an automated tool for reanalyzing genomic data in rare disease cohorts, showing improved diagnostic yields through iterative reanalysis.

Dominant variants in major spliceosome U4 and U5 small nuclear RNA genes cause neurodevelopmental disorders through splicing disruption

The paper identifies de novo variants in RNU4-2 and RNU5B-1 as causes of neurodevelopmental disorders by disrupting splicing, with variant location and allele phase influencing clinical severity.

A deep intronic variant in MME causes autosomal recessive Charcot-Marie-Tooth neuropathy through aberrant splicing

The paper identifies a deep intronic MME variant causing CMT through aberrant splicing, highlighting the importance of considering deep intronic variants in CMT diagnosis.

A rare splice-site variant in cardiac troponin-T (TNNT2): The need for ancestral diversity in genomic reference datasets

The paper reports a rare splice-site variant in TNNT2 found in Oceanian ancestry individuals, highlighting the need for diverse genomic datasets to avoid misclassification of variants.

Unique Capabilities of Genome Sequencing for Rare Disease Diagnosis

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.