David E. Root

This study provides structural insights into DHODH catalysis and drug resistance by analyzing conformational changes and resistance mutations.

This study evaluates strategies to inhibit XPR1 in ovarian cancer, showing that IP6K inhibitors effectively mimic XPR1 inhibition by blocking phosphate efflux and reducing tumor burden in xenograft models.

The paper presents a high-resolution map of RHO missense variants' trafficking and evaluates pharmacologic correction with YC-001, identifying pathogenic variants and therapeutic potential.

The paper identifies Aurora kinase A as a synthetic lethal target in FANCA-deficient cancers and shows AURKA inhibition induces chromosomal instability and G2/M arrest in these cells.

The paper identifies 25% of 7,264 non-canonical open reading frames (ncORFs) as producing translated gene products, supported by over 3,000 peptides from 3.8 billion mass spectra.

This study identifies two critical residues in FDX1 essential for both cuproptosis and lipoylation through deep mutational scanning.

The paper identifies O-mannosylation and protein maturation as therapeutic targets in BRAF fusion oncogenesis by showing their necessity for fusion-induced transformation.

The paper presents a comprehensive genetic perturbation dataset using Cell Painting to analyze gene expression effects in human cells, revealing novel gene clusters and functional relationships.

The paper identifies USP48 as a regulator of chromatin stability and DNA damage response to hypomethylating agents, showing its loss increases susceptibility to these drugs in AML.

This study identifies riboflavin as a critical metabolic dependency in acute myeloid leukemia, showing its role in nucleotide biosynthesis and iron-sulfur cluster metabolism beyond energy production.

This study creates a biliary tract cancer cell line atlas using multi-omics data to identify molecular subtypes and therapeutic targets.

This study uses deep mutational scanning to analyze KRAS variants, identifying gain- and loss-of-function mechanisms and their impact on oncogenic activity.

This study identifies a synergistic effect between AKT inhibitors and pitavastatin in killing triple-negative breast cancer cells by targeting cholesterol trafficking.

The paper identifies TYK2 as a potential therapeutic target for neurodegenerative diseases by linking cdsRNA-induced inflammation to interferon signaling and demonstrating protective effects of TYK2 inhibitors.

The paper introduces a dataset of cell morphology images treated with matched chemical and genetic perturbations and evaluates methods for identifying perturbation similarities.

Cell Painting images and profiles for 115,796 compounds in U2OS cells from 12 laboratories; 15.2% of analyzed compounds are phenotypically active, and cross-laboratory replicates cut reference-compound activity by 34%.

The paper introduces a method to screen large variant libraries with mutations across wide regions using improved mutant detection software, enabling accurate variant calling and counting from sequencing data.

Chronos infers gene knockout fitness effects by explicitly modelling cell proliferation dynamics after knockout, using longitudinal readouts and correcting several known screen biases.

The paper identifies Clp1-mediated 3’UTR shortening as a post-transcriptional mechanism enhancing transcript stability of Aire-sensitive genes in thymic medullary epithelial cells.

The paper performs a pooled loss-of-function screen in hematopoietic cells to identify genes underlying GWAS loci associated with red blood cell traits, finding 77 genes at 38 loci with biological relevance.

The paper evaluates and introduces optimized CRISPR libraries for knockout, interference, and activation screens, showing improved performance in gene function interrogation.

The paper improves gene dependency estimation from RNAi screens by using model-based normalization and data integration, enhancing accuracy and enabling cross-dataset analysis.

Molecular network analysis of RNA sequencing data from the aging human cortex identifies new Alzheimer's and cognitive decline genes.

The paper evaluates RNAi and CRISPR technologies by analyzing gene expression profiles in the Connectivity Map, finding that RNAi has strong off-target effects while CRISPR is more accurate.

The paper introduces the L1000 platform, a high-throughput gene expression profiling method, and reports 1.3 million perturbational profiles expanding the Connectivity Map for drug mechanism discovery and functional annotation.

The paper develops CERES, a computational method to correct copy-number effects in CRISPR-Cas9 essentiality screens, improving specificity in cancer cell line studies.