From CFTR to a CF signalling network: a systems biology approach to study Cystic Fibrosis.

Publisher: BioMed Central Country of Publication: England NLM ID: 100965258 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2164 (Electronic) Linking ISSN: 14712164 NLM ISO Abbreviation: BMC Genomics Subsets: MEDLINE

Original Publication: London : BioMed Central, [2000-

Cystic Fibrosis*/genetics ; Cystic Fibrosis*/metabolism ; Cystic Fibrosis Transmembrane Conductance Regulator*/genetics ; Cystic Fibrosis Transmembrane Conductance Regulator*/metabolism ; Systems Biology*/methods ; Signal Transduction*; Humans ; Phenotype ; Gene Regulatory Networks ; Gene Expression Profiling ; Transcriptome

Background: Cystic Fibrosis (CF) is a monogenic disease caused by mutations in the gene coding the Cystic Fibrosis Transmembrane Regulator (CFTR) protein, but its overall physio-pathology cannot be solely explained by the loss of the CFTR chloride channel function. Indeed, CFTR belongs to a yet not fully deciphered network of proteins participating in various signalling pathways.
Methods: We propose a systems biology approach to study how the absence of the CFTR protein at the membrane leads to perturbation of these pathways, resulting in a panel of deleterious CF cellular phenotypes.
Results: Based on publicly available transcriptomic datasets, we built and analyzed a CF network that recapitulates signalling dysregulations. The CF network topology and its resulting phenotypes were found to be consistent with CF pathology.
Conclusion: Analysis of the network topology highlighted a few proteins that may initiate the propagation of dysregulations, those that trigger CF cellular phenotypes, and suggested several candidate therapeutic targets. Although our research is focused on CF, the global approach proposed in the present paper could also be followed to study other rare monogenic diseases.
(© 2024. The Author(s).)

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Keywords: CF cellular phenotypes; CF signalling network; Cystic Fibrosis; Network topology; Therapeutic target

126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator)
0 (CFTR protein, human)

Date Created: 20240928 Date Completed: 20240929 Latest Revision: 20241002

20241002

PMC11438383

10.1186/s12864-024-10752-x

39342081