Using human genetics to improve safety assessment of therapeutics
Human genetics research has discovered thousands of proteins associated with complex
and rare diseases. Genome-wide association studies (GWAS) and studies of Mendelian …
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
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 …
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
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 …
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
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 …
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 …
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
Abstract Systems for CRISPR-based combinatorial perturbation of two or more genes are
emerging as powerful tools for uncovering genetic interactions. However, systematic …
emerging as powerful tools for uncovering genetic interactions. However, systematic …
Combined gene essentiality scoring improves the prediction of cancer dependency maps
Background Probing genetic dependencies of cancer cells can improve our understanding
of tumour development and progression, as well as identify potential drug targets. CRISPR …
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 …
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 …
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 …
proliferation, apoptosis, metabolism and DNA repair. PARP10 is overexpressed in a …