Yossi Farjoun

Multiplexed measurements of protein-protein interactions and protein abundance across cellular conditions using Prod&PQ-seq

Prod&PQ-seq detects and quantifies protein-protein interactions and protein abundance across different cellular conditions, showing changes in PRC2 interactions with EZH2 inhibition and H3 variants.

Exploring penetrance of clinically relevant variants in over 800,000 humans from the Genome Aggregation Database

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.

A genome-wide mutational constraint map quantified from variation in 76,156 human genomes

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.

Inferring compound heterozygosity from large-scale exome sequencing data

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

Alternative splicing in the lung influences COVID-19 severity and respiratory diseases.

This study identifies alternative splicing in lung genes as a factor influencing COVID-19 severity and respiratory diseases using Mendelian randomization.

Proteome-wide Mendelian randomization implicates nephronectin as an actionable mediator of the effect of obesity on COVID-19 severity

The paper identifies nephronectin as a mediator of obesity's effect on COVID-19 severity using proteome-wide Mendelian randomization and validates its expression in lung cells.

HLA allele-calling using whole-exome sequencing identifies 129 novel associations in 11 autoimmune diseases: a multi-ancestry analysis in the UK Biobank

This study uses whole-exome sequencing to directly call HLA alleles in the UK Biobank, identifying 129 novel associations between HLA alleles and 11 autoimmune diseases.

Cost-efficient whole genome-sequencing using novel mostly natural sequencing-by-synthesis chemistry and open fluidics platform

Open flow cell on a circular wafer with mostly natural nucleotides and no reversible terminators: about 300 bp reads at $1/Gb, 99.6% SNP accuracy on reference human genomes.

Detecting sample swaps in diverse NGS data types using linkage disequilibrium

Crosscheck detects mislabeled samples in NGS data by analyzing linkage disequilibrium, correcting errors in 1% of ENCODE datasets.

Evaluating potential drug targets through human loss-of-function genetic variation

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.

The mutational constraint spectrum quantified from variation in 141,456 humans

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.

Transcript expression-aware annotation improves rare variant discovery and interpretation

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.

An open resource of structural variation for medical and population genetics

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.

Human loss-of-function variants suggest that partial LRRK2 inhibition is a safe therapeutic strategy for Parkinsons disease

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.

Characterising the loss-of-function impact of 5’ untranslated region variants in 15,708 individuals

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

Landscape of multi-nucleotide variants in 125,748 human exomes and 15,708 genomes

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

Somatic Truth Data from Cell Lineage

The paper introduces a benchmark dataset of validated somatic mutations derived from cell lineage, providing a large collection of true somatic variation for use in mutation discovery pipelines.

Functional equivalence of genome sequencing analysis pipelines enables harmonized variant calling across human genetics projects

The paper defines functional equivalence standards for genome sequencing pipelines to enable harmonized variant calling across diverse datasets with minimal batch effects.

New synthetic-diploid benchmark for accurate variant calling evaluation

The paper introduces a new synthetic-diploid benchmark for variant calling accuracy, derived from de novo PacBio assemblies of homozygous human cell lines to reduce bias in error rate estimation.

Characterization and remediation of sample index swaps by non-redundant dual indexing on massively parallel sequencing platforms

The paper characterizes index swapping on Illumina sequencers and proposes dual indexing to mitigate its effects, showing varying swap rates across methods and sequencers.

Systematic comparison of monoclonal versus polyclonal antibodies for mapping histone modifications by ChIP-seq

This study compares monoclonal and polyclonal antibodies for ChIP-seq of histone modifications, finding monoclonals perform similarly in most cases but show differences for H3K27ac.