Kristian Cibulskis

The paper presents a large reference panel of 515,579 genomes to improve rare-variant imputation across underrepresented populations, enhancing accuracy for variants with frequencies as low as 0.002%.

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.

This paper introduces a service for automated cell type annotation in scRNA-seq data using reverse search against a curated database, providing both fine-grained and coarse annotations without relying on predefined markers.

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 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.

Mutect2 calls somatic SNVs and indels via local haplotype assembly, Bayesian genotyping and F-score-optimised filtering, with roughly one false call per 5 Mb in exome replicate-versus-replicate tests.

Four levers for cheaper cloud genomics on FireCloud: size virtual disks dynamically, tune VM provisioning from monitoring data, buy preemptible machines, and parallelise tasks at the right width.