Using human genetics to improve safety assessment of therapeutics

KJ Carss, AM Deaton, A Del Rio-Espinola… - Nature Reviews Drug …, 2023 - nature.com
Human genetics research has discovered thousands of proteins associated with complex
and rare diseases. Genome-wide association studies (GWAS) and studies of Mendelian …

Chronos: a cell population dynamics model of CRISPR experiments that improves inference of gene fitness effects

JM Dempster, I Boyle, F Vazquez, DE Root, JS Boehm… - Genome biology, 2021 - Springer
CRISPR loss of function screens are powerful tools to interrogate biology but exhibit a
number of biases and artifacts that can confound the results. Here, we introduce Chronos …

Capmatinib (INC280) is active against models of non–small cell lung cancer and other cancer types with defined mechanisms of MET activation

S Baltschukat, BS Engstler, A Huang, HX Hao… - Clinical Cancer …, 2019 - AACR
Purpose: The selective MET inhibitor capmatinib is being investigated in multiple clinical
trials, both as a single agent and in combination. Here, we describe the preclinical data of …

CRISPRi screens reveal a DNA methylation-mediated 3D genome dependent causal mechanism in prostate cancer

M Ahmed, F Soares, JH Xia, Y Yang, J Li, H Guo… - Nature …, 2021 - nature.com
Prostate cancer (PCa) risk-associated SNPs are enriched in noncoding cis-regulatory
elements (rCREs), yet their modi operandi and clinical impact remain elusive. Here, we …

A benchmark of computational methods for correcting biases of established and unknown origin in CRISPR-Cas9 screening data

A Vinceti, RM Iannuzzi, I Boyle, L Trastulla… - Genome Biology, 2024 - Springer
Background CRISPR-Cas9 dropout screens are formidable tools for investigating biology
with unprecedented precision and scale. However, biases in data lead to potential …

GEMINI: a variational Bayesian approach to identify genetic interactions from combinatorial CRISPR screens

M Zamanighomi, SS Jain, T Ito, D Pal, TP Daley… - Genome biology, 2019 - Springer
Abstract Systems for CRISPR-based combinatorial perturbation of two or more genes are
emerging as powerful tools for uncovering genetic interactions. However, systematic …

Combined gene essentiality scoring improves the prediction of cancer dependency maps

W Wang, A Malyutina, A Pessia, J Saarela… - …, 2019 - thelancet.com
Background Probing genetic dependencies of cancer cells can improve our understanding
of tumour development and progression, as well as identify potential drug targets. CRISPR …

An interactive web application for processing, correcting, and visualizing genome-wide pooled CRISPR-Cas9 screens

A Vinceti, RR De Lucia, P Cremaschi, U Perron… - Cell Reports …, 2023 - cell.com
A limitation of pooled CRISPR-Cas9 screens is the high false-positive rate in detecting
essential genes arising from copy-number-amplified genomics regions. To solve this issue …

Genome-wide CRISPR guide RNA design and specificity analysis with GuideScan2

H Schmidt, M Zhang, H Mourelatos, FJ Sánchez-Rivera… - bioRxiv, 2022 - biorxiv.org
We present GuideScan2 for memory-efficient, parallelizable construction of high-specificity
CRISPR guide RNA (gRNA) databases and user-friendly gRNA/library design in custom …

[HTML][HTML] Complementary CRISPR genome-wide genetic screens in PARP10-knockout and overexpressing cells identify synthetic interactions for PARP10-mediated …

JB Khatib, EM Schleicher, LM Jackson, A Dhoonmoon… - Oncotarget, 2022 - ncbi.nlm.nih.gov
PARP10 is a mono-ADP-ribosyltransferase with multiple cellular functions, including
proliferation, apoptosis, metabolism and DNA repair. PARP10 is overexpressed in a …