Network Proximity-Based Drug Repurposing Strategy for Early and Late Stages of Primary Biliary Cholangitis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Disease-Associated Gene Data Gathering
2.2. Network-Based Putative Disease Gene Prioritization
2.3. Functional Annotation
3. Results
3.1. Identification of Seed Genes
3.2. Over-Representation Analysis (ORA)
3.3. Drug Repurposing
3.3.1. Seed Gene Drug Repurposing ORA
3.3.2. In Silico Gene Drug Repurposing ORA
3.4. Pathway Analysis
3.4.1. Seed Gene Pathway ORA
3.4.2. In Silico Gene Pathway ORA
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
APU | adaptive positive-unlabelled |
BCAAs | branched-chain amino acids |
DAGs | disease-associated genes |
EGFR | epidermal growth factor receptor |
FDR | false discovery rate |
FXR | farnesoid X receptor |
LP | likely positives |
ML | machine learning |
NF-kB | nuclear factor kappa B |
ORA | over-representation analysis |
PBC | primary biliary cholangitis |
PEICT | phenethyl isothiocyanate |
PI3K | phosphoinositide 3-kinase |
PPI | protein–protein interaction |
PKI | protein kinase inhibitors |
PSC | primary sclerosing cholangitis |
UDCA | ursodeoxycholic acid |
US | unspecified stages |
TLR | Toll-like receptor |
TLR4 | Toll-like receptor-4 |
TUDCA | tauroursodeoxycholic acid |
WebGestalt | WEB-based Gene Set Analysis Toolkit |
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Shahini, E.; Pasculli, G.; Mastropietro, A.; Stolfi, P.; Tieri, P.; Vergni, D.; Cozzolongo, R.; Pesce, F.; Giannelli, G. Network Proximity-Based Drug Repurposing Strategy for Early and Late Stages of Primary Biliary Cholangitis. Biomedicines 2022, 10, 1694. https://doi.org/10.3390/biomedicines10071694
Shahini E, Pasculli G, Mastropietro A, Stolfi P, Tieri P, Vergni D, Cozzolongo R, Pesce F, Giannelli G. Network Proximity-Based Drug Repurposing Strategy for Early and Late Stages of Primary Biliary Cholangitis. Biomedicines. 2022; 10(7):1694. https://doi.org/10.3390/biomedicines10071694
Chicago/Turabian StyleShahini, Endrit, Giuseppe Pasculli, Andrea Mastropietro, Paola Stolfi, Paolo Tieri, Davide Vergni, Raffaele Cozzolongo, Francesco Pesce, and Gianluigi Giannelli. 2022. "Network Proximity-Based Drug Repurposing Strategy for Early and Late Stages of Primary Biliary Cholangitis" Biomedicines 10, no. 7: 1694. https://doi.org/10.3390/biomedicines10071694
APA StyleShahini, E., Pasculli, G., Mastropietro, A., Stolfi, P., Tieri, P., Vergni, D., Cozzolongo, R., Pesce, F., & Giannelli, G. (2022). Network Proximity-Based Drug Repurposing Strategy for Early and Late Stages of Primary Biliary Cholangitis. Biomedicines, 10(7), 1694. https://doi.org/10.3390/biomedicines10071694