Beryl B. Cummings

The paper analyzes over 800,000 human genomes to assess penetrance of clinically relevant variants, finding that 95% of pLoF variants in severe diseases have explanations for lack of disease manifestation.

Rare-variant depletion in 1kb windows of 76,156 gnomAD genomes, versus feature-adjusted mutation expectations, marks regulatory elements and outperforms seven alternative scores at flagging functional non-coding variants.

The paper develops a method to infer compound heterozygosity from exome sequencing data, achieving high accuracy in phasing rare variants for recessive disease diagnosis.

The paper uses long-read RNA-seq data to identify new transcripts and develop a tool to analyze genetic effects on transcript structure, revealing insights into splicing regulation and variant interpretation.

This study shows that TDP-43 represses a cryptic exon in UNC13A, and genetic variants associated with FTD/ALS increase cryptic exon inclusion when TDP-43 is dysfunctional.

The paper describes the role of the Centers for Mendelian Genomics in advancing gene discovery through data sharing, collaboration, and resource development over the past decade.

The paper evaluates potential drug targets using loss-of-function genetic variants from gnomAD, highlighting the importance of deep curation and targeted recall studies for drug discovery.

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.

Short-read genome sequencing of 14,891 diverse genomes yields 433,371 structural variants (SVs) for gnomAD; loss-constrained genes also resist duplication, and clinical SV carrier rates are benchmarked.

The paper analyzes loss-of-function variants in LRRK2 across large genomic datasets to assess the safety of partial LRRK2 inhibition as a Parkinson's disease therapy.

The paper systematically studies uORF variants in 15,708 genomes, showing they are under strong negative selection and contribute to disease.

The paper analyzes multi-nucleotide variants (MNVs) in 125,748 exomes and 15,708 genomes, identifying their distribution, mutational origins, and functional implications.

The paper identifies genomic variants regulating junction-skipping using RNA-seq and GWAS data to understand their role in complex diseases.

ANEVA quantifies genetic regulatory variation using allelic expression data, improving transcriptome analysis and aiding in rare disease diagnosis.

The paper uses an OU process to model gene expression evolution across mammals and identifies expression pathways under different selection pressures.

This study identifies genetic mutations in 78% of Diamond-Blackfan anemia patients using whole exome sequencing, finds new RP genes, and reports genotype-phenotype associations.

The paper develops S-PrediXcan to compute gene expression associations from GWAS summary data and applies it to 44 GTEx tissues and 100+ phenotypes, finding tissue-specific effects and colocalized associations.

Transcriptome sequencing improves the diagnostic rate for Mendelian disease in patients for whom genetic analysis has not returned a diagnosis.

This paper systematically surveys X chromosome inactivation across human tissues using transcriptomic and genomic data, finding that XCI is generally uniform but shows heterogeneity and identifies new escape genes with sex-biased expression.