Frederick P. Roth

The paper evaluates imputation methods for contextual variant effects in MAVE studies, finding that method choice depends on data density and task requirements.

This study proactively evaluates the functional effects of 9790 AIRE missense variants using a reporter assay, providing evidence for 70% of previously classified variants of uncertain significance.

The paper investigates E-rich domain variants of RBM20, showing they reduce protein abundance and cause splicing defects, but are not rescued by RBM20 overexpression.

The paper evaluates how different truthset strategies affect evidence points (EPs) in clinical validation of functional assays across 2,120 gene-truthset-assay combinations.

The paper establishes consensus guidelines for constructing truthsets to validate functional assays in cancer variant interpretation, focusing on missense variants and clinical validation frameworks.

The paper develops a multidimensional assay to assess variant effects in MYBPC3, reclassifying variants and uncovering disease mechanisms in hypertrophic cardiomyopathy.

The paper systematically assesses the functional impact of CPOX variants under different environmental conditions, revealing mercury-dependent variant effects and improving variant classification.

The paper introduces VIS-seq, an image-based method to assess variant effects on cellular phenotypes, revealing multidimensional variant impacts across different diseases.

The paper investigates how dual-role regulators interact with the Sin3 complex using structural and functional analyses, revealing mechanisms for transcriptional crosstalk.

The paper develops a scalable workflow to reclassify variants of uncertain significance using experimental and predictive evidence, resolving 75% of VUS in 40 genes.

The paper maps the functional landscape of KCNQ1 variants to identify pathogenic and benign variants, revealing their impact on arrhythmia risk and ion channel mechanisms.

The paper measures the functional impact of over two thousand SOD1 missense variants using saturation mutagenesis and cell-based assays, reclassifying 41% of previously uncertain variants as pathogenic.

This study creates a proteome-wide gain-of-function atlas to map chemotherapy responses and identifies drug combinations to overcome resistance.

This study functionally tests STK11 missense variants in mammalian cells, identifying pathogenic variants and providing insights for clinical interpretation.

The paper constructs a genome-scale genetic interaction network from 4 million double mutants in HAP1 cells, revealing conserved genetic network principles across species and uncovering novel gene functions and cancer dependencies.

The paper uses a yeast two-hybrid screen to identify novel effector-effector interactions in L. pneumophila, doubling the known number of such interactions.

This paper evaluates how functional variant data and penetrance estimates improve risk stratification for LQTS in KCNH2 missense variant carriers.

The paper evaluates computational predictors for rare variant burden tests and identifies two top predictors that enhance gene-trait association discovery in the UK Biobank.

Pacybara improves the accuracy of long-read sequencing for barcoded mutagenized libraries by addressing sequencing errors and non-unique barcodes.

This study uses cancer mutation data and machine learning to predict the pathogenicity of germline missense variants, showing strong performance in identifying disease-causing variants.

The paper creates a functional map of all possible missense variants in CHK2 to assess their impact on cancer risk.

This study systematically tests HMBS missense variants to determine their functional impact and distinguish pathogenic from benign variants.

This study maps human glucokinase variant activity using a yeast complementation assay, identifying activity patterns linked to disease and providing insights for variant interpretation and therapeutic development.

satmut_utils is a tool for simulating and analyzing saturation mutagenesis data, showing that single-codon variants can alter mRNA abundance and demonstrating improved variant calling performance.

The paper maps binary SARS-CoV-2 protein interactions with host proteins, identifying key processes like immune signaling and ubiquitination, and suggests therapeutic targets.

The paper identifies 160 genes that suppress DNA damage in human cells through CRISPR/Cas9 screens, highlighting GNB1L's role in ATR biogenesis and its link to neuropsychiatric disorders.

This study creates a variant effect map for GDI1 missense variants using functional assays and machine learning to distinguish pathogenic from benign variants.

MaveRegistry is a platform for tracking and sharing multiplexed variant effect assays to reduce redundancy and enable collaboration in variant interpretation.

The paper constructs a high-quality yeast binary interactome map and compares inner- and outer-complexome organization, finding the outer-complexome contains more interactions and exhibits higher functional heterogeneity.

Proximity-dependent biotinylation of 27 SARS-CoV-2 proteins in A549 cells maps 7810 virus-host proximity interactions across 2242 host proteins, including membrane-associated partners missed by affinity purification.