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In silico discovery of the blood cell interactome [microRNA]

ABSTRACT: The aim of the present study identify putative macromolecular interactions in human peripheral blood based on significant correlations at the transcriptional level. We found that significant transcript correlations within a giant matrix including also mRNAs from the same project reflect experimentally documented interactions

ORGANISM(S): Homo sapiens

PROVIDER: GSE198933 | GEO | 2022/03/21

REPOSITORIES: GEO

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Project description:BackgroundThe emergence and spread of malaria drug resistance have resulted in the need to understand disease mechanisms and importantly identify essential targets and potential drug candidates. Malaria infection involves the complex interaction between the host and pathogen, thus, functional interactions between human and Plasmodium falciparum is essential to obtain a holistic view of the genetic architecture of malaria. Several functional interaction studies have extended the understanding of malaria disease and integrating such datasets would provide further insights towards understanding drug resistance and/or genetic resistance/susceptibility, disease pathogenesis, and drug discovery.MethodsThis study curated and analysed data including pathogen and host selective genes, host and pathogen protein sequence data, protein-protein interaction datasets, and drug data from literature and databases to perform human-host and P. falciparum network-based analysis. An integrative computational framework is presented that was developed and found to be reasonably accurate based on various evaluations, applications, and experimental evidence of outputs produced, from data-driven analysis.ResultsThis approach revealed 8 hub protein targets essential for parasite and human host-directed malaria drug therapy. In a semantic similarity approach, 26 potential repurposable drugs involved in regulating host immune response to inflammatory-driven disorders and/or inhibiting residual malaria infection that can be appropriated for malaria treatment. Further analysis of host-pathogen network shortest paths enabled the prediction of immune-related biological processes and pathways subverted by P. falciparum to increase its within-host survival.ConclusionsHost-pathogen network analysis reveals potential drug targets and biological processes and pathways subverted by P. falciparum to enhance its within malaria host survival. The results presented have implications for drug discovery and will inform experimental studies.

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In silico discovery of the blood cell interactome [microRNA]

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