Brian J. O’Roak

Detailed phenotyping of Tbr1-2A-CreER knock-in mice demonstrates significant impacts on TBR1 protein levels and axon development

This study evaluates the Tbr1-2A-CreER knock-in mouse line, showing reduced TBR1 protein levels and axon development issues, indicating it is a hypomorphic allele with implications for neurodevelopmental research.

Integrating de novo and inherited variants in over 42,607 autism cases identifies mutations in new moderate risk genes

The paper identifies 60 new moderate risk genes for autism by integrating de novo and inherited variants across 42,607 cases and 236,000 controls.

Shared and distinct functional effects of patient-specific Tbr1 mutations on cortical development

This study examines the functional effects of two patient-specific Tbr1 mutations on cortical development in mice, revealing both shared and distinct phenotypes.

Cas12a-Capture: a novel, low-cost, and scalable method for targeted sequencing

The paper introduces Cas12a-Capture, a low-cost, scalable targeted sequencing method that reduces GC bias and improves variant calling accuracy.

High-content single-cell combinatorial indexing

This paper introduces a novel adaptor-switching strategy, s3, that significantly improves usable reads per cell in single-cell genomics assays while maintaining high-throughput capabilities.

An integrated deep mutational scanning approach provides clinical insights on PTEN genotype-phenotype relationships

This study combines deep mutational scanning data with clinical data to link PTEN variants to specific clinical outcomes and risk levels.

Exome sequencing of 457 autism families recruited online provides evidence for novel ASD genes

The paper reports exome sequencing of 457 ASD families, identifying 10.4% with known ASD genes and 3.4% with possibly associated variants, and provides statistical support for 34 ASD risk genes using the TADA framework.

Mutually exclusive autism mutations point to the circadian clock and PI3K signaling pathways

The paper identifies mutual exclusivity patterns in de novo mutations in autism spectrum disorder, linking them to circadian clock and PI3K/AKT signaling pathways.

Improved single-cell ATAC-seq reveals chromatin dynamics of in vitro corticogenesis

The paper introduces an improved single-cell ATAC-seq method, scip-ATAC-seq, which enhances chromatin dynamics analysis in human corticogenesis organoids.

A saturation mutagenesis approach to understanding PTEN lipid phosphatase activity and genotype-phenotypes relationships

The paper uses a saturation mutagenesis approach in a yeast model to assess PTEN variants' impact on lipid phosphatase activity, identifying functional scores for 7,244 variants and reclassifying some ClinVar unclassified variants.

Scalable and efficient single-cell DNA methylation sequencing by combinatorial indexing.

The paper introduces sci-MET, a scalable single-cell DNA methylation sequencing method, achieving 69% read alignment rates and successfully deconvolving a mixture of three human cell lines.

Exonic mosaic mutations contribute risk for autism spectrum disorder

The paper investigates exonic mosaic mutations in autism spectrum disorder (ASD) using whole-exome sequencing data from the Simons Simplex Collection, finding significant synonymous SMM burden and enrichment in chromatin modifiers.