Predicting and characterizing a cancer dependency map of tumors with deep learning DOI Creative Commons
Yu‐Chiao Chiu, Siyuan Zheng, Li‐Ju Wang

et al.

Science Advances, Journal Year: 2021, Volume and Issue: 7(34)

Published: Aug. 20, 2021

A novel deep learning method links in vitro CRISPR screens to the context of cancer genomics and translates individual tumors.

Language: Английский

Drug combinations: a strategy to extend the life of antibiotics in the 21st century DOI
Mike Tyers, Gerard D. Wright

Nature Reviews Microbiology, Journal Year: 2019, Volume and Issue: 17(3), P. 141 - 155

Published: Jan. 25, 2019

Language: Английский

Citations

677
Overcoming cancer therapeutic bottleneck by drug repurposing DOI Creative Commons
Zhe Zhang, Li Zhou, Na Xie

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: July 2, 2020

Abstract Ever present hurdles for the discovery of new drugs cancer therapy have necessitated development alternative strategy drug repurposing, old therapeutic purposes. This with a cost-effective way offers rare opportunity treatment human neoplastic disease, facilitating rapid clinical translation. With an increased understanding hallmarks and various data-driven approaches, repurposing further promotes holistic productivity reasonably focuses on target-defined antineoplastic compounds. The “treasure trove” non-oncology should not be ignored since they could target only known but also hitherto unknown vulnerabilities cancer. Indeed, different from targeted drugs, these generic usually used in multi-target may bring benefit to patients. In this review, aiming demonstrate full potential we promising repurposed management classify candidates into their proposed administration either mono- or combination therapy. We summarize approaches discuss main barriers its uptake.

Language: Английский

Citations

431
Synthetic lethal therapies for cancer: what’s next after PARP inhibitors? DOI
Alan Ashworth, Christopher J. Lord

Nature Reviews Clinical Oncology, Journal Year: 2018, Volume and Issue: 15(9), P. 564 - 576

Published: June 28, 2018

Language: Английский

Citations

368
Global Genetic Networks and the Genotype-to-Phenotype Relationship DOI Creative Commons
Michael Costanzo, Elena Kuzmin, Jolanda van Leeuwen

et al.

Cell, Journal Year: 2019, Volume and Issue: 177(1), P. 85 - 100

Published: March 1, 2019

Language: Английский

Citations

218
Pangenomics Comes of Age: From Bacteria to Plant and Animal Applications DOI
Agnieszka A. Golicz, Philipp E. Bayer, Prem L. Bhalla

et al.

Trends in Genetics, Journal Year: 2019, Volume and Issue: 36(2), P. 132 - 145

Published: Dec. 24, 2019

Language: Английский

Citations

191
Targeting pan-essential genes in cancer: Challenges and opportunities DOI Creative Commons
Liang Chang, Paloma Ruiz, Takahiro Ito

et al.

Cancer Cell, Journal Year: 2021, Volume and Issue: 39(4), P. 466 - 479

Published: Jan. 15, 2021

Language: Английский

Citations

141
The impact of genetic diversity on gene essentiality within the Escherichia coli species DOI
François Rousset, Jose Cabezas-Caballero,

Florence Piastra-Facon

et al.

Nature Microbiology, Journal Year: 2021, Volume and Issue: 6(3), P. 301 - 312

Published: Jan. 18, 2021

Language: Английский

Citations

119
CRISPR screens in physiologic medium reveal conditionally essential genes in human cells DOI Creative Commons
Nicholas J. Rossiter, Kimberly S. Huggler, Charles H. Adelmann

et al.

Cell Metabolism, Journal Year: 2021, Volume and Issue: 33(6), P. 1248 - 1263.e9

Published: March 1, 2021

Language: Английский

Citations

115
A bacterial pan-genome makes gene essentiality strain-dependent and evolvable DOI Creative Commons
Federico Rosconi,

Emily Rudmann,

Jien Li

et al.

Nature Microbiology, Journal Year: 2022, Volume and Issue: 7(10), P. 1580 - 1592

Published: Sept. 12, 2022

Many bacterial species are represented by a pan-genome, whose genetic repertoire far outstrips that of any single genome. Here we investigate how pan-genome might influence gene essentiality and whether essential genes initially critical for the survival an organism can evolve to become non-essential. By using Transposon insertion sequencing (Tn-seq), whole-genome RNA-seq on set 36 clinical Streptococcus pneumoniae strains representative >68% species' identify species-wide 'essentialome' be subdivided into universal, core strain-specific accessory genes. employing 'forced-evolution experiments', show specific changes allow bacteria bypass essentiality. Moreover, untangling several mechanisms, highly influenced and/or dependent on: (1) composition genome, (2) accumulation toxic intermediates, (3) functional redundancy, (4) efficient recycling metabolites (5) pathway rewiring. While this characterization underscores evolvability potential many genes, also with differential remain important antimicrobial drug target candidates, as their inactivation almost always has severe fitness cost in vivo.

Language: Английский

Citations

82
Changing fitness effects of mutations through long-term bacterial evolution DOI
Alejandro Couce, Anurag Limdi, Mélanie Magnan

et al.

Science, Journal Year: 2024, Volume and Issue: 383(6681)

Published: Jan. 25, 2024

The distribution of fitness effects new mutations shapes evolution, but it is challenging to observe how changes as organisms adapt. Using

Language: Английский

Citations

26