Jason Moffat

Quantitative analysis of genetic interactions in human cells from genome-wide CRISPR-Cas9 screens

The paper develops a method to quantify genetic interactions from CRISPR-Cas9 screens and identifies systematic variations in screen data.

A global genetic interaction map of a human cell reveals conserved principles of genetic networks

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.

Integrated genetic screening reveals FEN1 as a driver of stemness and temozolomide resistance in glioblastoma

This study identifies FEN1 as a driver of glioblastoma stem cell survival and temozolomide resistance, showing FEN1 inhibition can enhance TMZ efficacy in aggressive tumors.

TSC22D, WNK and NRBP gene families exhibit functional buffering and evolved with Metazoa for macromolecular crowd sensing

This study identifies functional relationships between TSC22D, WNK, and NRBP gene families in macromolecular crowding sensing and cell volume regulation across metazoans.

A scalable platform for efficient CRISPR-Cas9 chemical-genetic screens of DNA damage-inducing compounds

The paper presents a scalable CRISPR-Cas9 platform for chemical-genetic screens of DNA damage-inducing compounds, identifying enriched modes-of-action and revealing late ICL repair pathway responses.

N-terminal acetylation shields proteins from degradation and promotes age-dependent motility and longevity

The paper shows that N-terminal acetylation by NatC protects proteins from degradation, enhancing longevity and motility, and that UBR4-KCMF1 targets unacetylated N-terminal Met followed by hydrophobic residues.

A cohesin traffic pattern genetically linked to gene regulation

The paper identifies three types of chromatin boundaries that regulate cohesin traffic, which guides enhancer-promoter interactions and affects gene regulation.

Multi-level cellular and functional annotation of single-cell transcriptomes

The paper introduces scPipeline, a tool for multi-level cellular and functional annotation of scRNA-seq data, validated across diverse datasets.

Reproducibility metrics for CRISPR screens

The paper identifies limitations in current reproducibility metrics for CRISPR screens and advocates for context-sensitive metrics to better assess screen quality.

Systematic genome-scale identification of host factors for SARS-CoV-2 infection across models yields a core single gene dependency; ACE2

The paper identifies ACE2 as the only common host dependency for SARS-CoV-2 across multiple cell lines, while other host factors are cell line specific.

Major functional bias for mitochondrial complexes in genome-wide CRISPR screens

The paper introduces FLEX, a pipeline for benchmarking CRISPR screen data, and identifies a dominant mitochondria-associated signal in genome-wide screens.

Systematic mapping of genetic interactions for de novo fatty acid synthesis

This study maps genetic interactions in FASN-deficient cells to identify genes involved in lipid uptake and metabolic adaptation.

Cell cycle regulation of mitochondrial protein import revealed by genome-scale pooled bimolecular fluorescence complementation screening

The paper introduces MaGiCaL-BiFC, a method to identify protein-protein interactions in mammalian cells, and uses it to find novel interactions involving TOMM22, including a mitosis-specific interaction with CK2.

Scalable, FACS-Free Genome-Wide Phenotypic Screening

The paper presents a high-throughput CRISPR-Cas9 screening method for identifying CD47 modulators, identifying QPCTL as a key enzyme involved in its pyroglutamyl modification.

Identifying chemogenetic interactions from CRISPR knockout screens with drugZ

drugZ identifies chemogenetic interactions from CRISPR screens, finding more homologous recombination repair pathway genes and confirming KEAP1 loss as a resistance factor for ERK inhibitors.

Coessentiality And Cofunctionality: A Network Approach To Learning Genetic Vulnerabilities From Cancer Cell Line Fitness Screens

The paper develops a network approach to identify genetic vulnerabilities in cancer cell lines by analyzing shRNA screens and clustering coessential genes to discover context-specific essential genes and biomarkers.

Evaluation and Design of Genome-wide CRISPR/Cas9 Knockout Screens

The paper evaluates CRISPR/Cas9 knockout screens in human cell lines and designs an optimized gRNA library to improve gene knockout efficiency and accuracy.

BAGEL: A computational framework for identifying essential genes from pooled library screens.

BAGEL identifies essential genes from pooled CRISPR screens with high sensitivity and specificity, improving upon existing methods by 10-fold in runtime and accuracy.

A CRISPR screen reveals a WNT7B-FZD5 signaling circuit as a therapeutic opportunity in pancreatic cancer.

The paper identifies a WNT7B-FZD5 signaling circuit as a therapeutic target in pancreatic cancer using CRISPR screening and validates it with antibodies.

Systematic discovery and classification of human cell line essential genes

This study identifies and classifies human cell line essential genes using an optimized CRISPR-Cas9 screen, finding twice to thrice as many essential genes as previous RNAi studies.

Measuring error rates in genomic perturbation screens: gold standards for human functional genomics

This paper develops a Bayesian classifier to improve gene essentiality analysis in genomic perturbation screens and shows CRISPR is more sensitive than RNAi with manageable false discovery rates.