The cellular response to drug perturbation is limited: comparison of large-scale chemogenomic fitness signatures.
BMC Genomics
; 23(1): 197, 2022 Mar 11.
Article
em En
| MEDLINE
| ID: mdl-35277135
ABSTRACT
BACKGROUND:
Chemogenomic profiling is a powerful approach for understanding the genome-wide cellular response to small molecules. First developed in Saccharomyces cerevisiae, chemogenomic screens provide direct, unbiased identification of drug target candidates as well as genes required for drug resistance. While many laboratories have performed chemogenomic fitness assays, few have been assessed for reproducibility and accuracy. Here we analyze the two largest independent yeast chemogenomic datasets comprising over 35 million gene-drug interactions and more than 6000 unique chemogenomic profiles; the first from our own academic laboratory (HIPLAB) and the second from the Novartis Institute of Biomedical Research (NIBR).RESULTS:
Despite substantial differences in experimental and analytical pipelines, the combined datasets revealed robust chemogenomic response signatures, characterized by gene signatures, enrichment for biological processes and mechanisms of drug action. We previously reported that the cellular response to small molecules is limited and can be described by a network of 45 chemogenomic signatures. In the present study, we show that the majority of these signatures (66%) are also found in the companion dataset, providing further support for their biological relevance as conserved systems-level, small molecule response systems.CONCLUSIONS:
Our results demonstrate the robustness of chemogenomic fitness profiling in yeast, while offering guidelines for performing other high-dimensional comparisons including parallel CRISPR screens in mammalian cells.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Saccharomyces cerevisiae
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
BMC Genomics
Assunto da revista:
GENETICA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Canadá