An automated network-based tool to search for metabolic vulnerabilities in cancer.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
11 Oct 2024
11 Oct 2024
Historique:
received:
22
06
2022
accepted:
18
09
2024
medline:
12
10
2024
pubmed:
12
10
2024
entrez:
11
10
2024
Statut:
epublish
Résumé
The development of computational tools for the systematic prediction of metabolic vulnerabilities of cancer cells constitutes a central question in systems biology. Here, we present gmctool, a freely accessible online tool that allows us to accomplish this task in a simple, efficient and intuitive environment. gmctool exploits the concept of genetic Minimal Cut Sets (gMCSs), a theoretical approach to synthetic lethality based on genome-scale metabolic networks, including a unique database of synthetic lethals computed from Human1, the most recent metabolic reconstruction of human cells. gmctool introduces qualitative and quantitative improvements over our previously developed algorithms to predict, visualize and analyze metabolic vulnerabilities in cancer, demonstrating a superior performance than competing algorithms. A detailed illustration of gmctool is presented for multiple myeloma (MM), an incurable hematological malignancy. We provide in vitro experimental evidence for the essentiality of CTPS1 (CTPS synthase) and UAP1 (UDP-N-Acetylglucosamine Pyrophosphorylase 1) in specific MM patient subgroups.
Identifiants
pubmed: 39394196
doi: 10.1038/s41467-024-52725-4
pii: 10.1038/s41467-024-52725-4
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8685Subventions
Organisme : Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness)
ID : PID2019-110344RB-I00, PID2022-143298OB-I00
Informations de copyright
© 2024. The Author(s).
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