Brian H. Shirts

Insights on improving accessibility and usability of functional data to unlock its potential for variant interpretation

This study identifies barriers to using functional data in clinical variant interpretation and highlights the need for better access and standardized interpretation guidelines.

Applying health equity implementation science frameworks to population genetic screening

This paper explores the application of health equity implementation science frameworks to guide the equitable implementation of population genetic screening programs.

A maternal germline mutator phenotype in a family affected by heritable colorectal cancer

The paper measures germline mutation rates in a family with MUTYH pathogenic variants, finding elevated C>A mutations in children of affected mothers but not fathers, suggesting maternal-specific mutator effects.

Assigning credit where it's due: An information content score to capture the clinical value of Multiplexed Assays of Variant Effect

The paper introduces an information content score to quantify the clinical value of MAVEs, showing it captures more information than just reclassifying variants.

Diagnostic yield of genetic screening in a diverse, community-ascertained cohort

This study evaluates the diagnostic yield and enrollment rates of population genetic screening in a diverse cohort, finding 2.6% actionable genetic findings but challenges in recruitment and sample collection.

Modeling the impact of data sharing on variant classification

The paper models how data sharing affects the classification of genetic variants, showing higher classification probabilities with shared data over time.

Using species richness calculations to model the global profile of unsampled pathogenic variants: examples from BRCA1 and BRCA2

The paper estimates the number of unobserved pathogenic BRCA1/2 variants globally using ecological species richness methods and finds 45-88% of variants are missing in study data.

ClinGen CDH1 specifications for the ACMG/AMP guidelines: improvement of germline variant clinical assertions and updated curation guidelines

The paper updates CDH1 variant curation guidelines to resolve conflicting interpretations and reduce variants of uncertain significance for clinical use.

One in seven pathogenic variants can be challenging to detect by NGS: An analysis of 450,000 patients with implications for clinical sensitivity and genetic test implementation

The paper evaluates the detection of technically challenging variants in NGS workflows using synthetic specimens and clinical data from 450,000 patients, finding significant variability in detection rates.

Multiplexing Mutation Rate Assessment: Determining Pathogenicity of Msh2 Variants in S. cerevisiae

The paper introduces a high-throughput method to assess mutation rates in yeast strains with Msh2 mutations, identifying pathogenic variants by linking mutations to DNA repair gene alleles.

An interlaboratory study of complex variant detection

This study evaluates synthetic specimens with challenging variants across 10 NGS workflows, finding limited variant detection consistency and highlighting bioinformatic limitations.