Network-driven analysis of human–Plasmodium falciparum interactome: processes for malaria drug discovery and extracting in silico targets
| dc.contributor.author | Agamah, Francis E. | |
| dc.contributor.author | Damena, Delesa | |
| dc.contributor.author | Skelton, Michelle | |
| dc.contributor.author | Ghansah, Anita | |
| dc.contributor.author | Mazandu, Gaston K. | |
| dc.contributor.author | Chimusa, Emile R. | |
| dc.date.accessioned | 2021-11-02T13:01:23Z | |
| dc.date.available | 2021-11-02T13:01:23Z | |
| dc.date.issued | 2021-10-26 | |
| dc.date.updated | 2021-10-31T04:18:36Z | |
| dc.description.abstract | Background The 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. Methods This 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. Results This 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. Conclusions Host–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. | en_US |
| dc.identifier.apacitation | Agamah, Francis E., Damena, D., Skelton, M., Ghansah, A., Mazandu, Gaston K., & Chimusa, Emile R. (2021). Network-driven analysis of human–Plasmodium falciparum interactome: processes for malaria drug discovery and extracting in silico targets. <i>Malaria Journal</i>, 20(Article number: 421), http://hdl.handle.net/11427/35303 | en_ZA |
| dc.identifier.chicagocitation | Agamah, Francis E., Delesa Damena, Michelle Skelton, Anita Ghansah, Gaston K. Mazandu, and Emile R. Chimusa "Network-driven analysis of human–Plasmodium falciparum interactome: processes for malaria drug discovery and extracting in silico targets." <i>Malaria Journal</i> 20, Article number: 421. (2021) http://hdl.handle.net/11427/35303 | en_ZA |
| dc.identifier.citation | Agamah, Francis E., Damena, D., Skelton, M., Ghansah, A., Mazandu, Gaston K. & Chimusa, Emile R. 2021. Network-driven analysis of human–Plasmodium falciparum interactome: processes for malaria drug discovery and extracting in silico targets. <i>Malaria Journal.</i> 20(Article number: 421) http://hdl.handle.net/11427/35303 | en_ZA |
| dc.identifier.ris | TY - Journal Article AU - Agamah, Francis E. AU - Damena, Delesa AU - Skelton, Michelle AU - Ghansah, Anita AU - Mazandu, Gaston K. AU - Chimusa, Emile R. AB - Background The 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. Methods This 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. Results This 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. Conclusions Host–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. DA - 2021-10-26 DB - OpenUCT DP - University of Cape Town IS - Article number: 421 J1 - Malaria Journal KW - Malaria KW - Drug resistance KW - Genomics KW - Multi-omics KW - Gene ontology KW - Protein–protein interaction LK - https://open.uct.ac.za PY - 2021 T1 - Network-driven analysis of human–Plasmodium falciparum interactome: processes for malaria drug discovery and extracting in silico targets TI - Network-driven analysis of human–Plasmodium falciparum interactome: processes for malaria drug discovery and extracting in silico targets UR - http://hdl.handle.net/11427/35303 ER - | en_ZA |
| dc.identifier.uri | https://doi.org/10.1186/s12936-021-03955-0 | |
| dc.identifier.uri | http://hdl.handle.net/11427/35303 | |
| dc.identifier.vancouvercitation | Agamah Francis E, Damena D, Skelton M, Ghansah A, Mazandu Gaston K, Chimusa Emile R. Network-driven analysis of human–Plasmodium falciparum interactome: processes for malaria drug discovery and extracting in silico targets. Malaria Journal. 2021;20(Article number: 421) http://hdl.handle.net/11427/35303. | en_ZA |
| dc.language.iso | en | en_US |
| dc.language.rfc3066 | en | |
| dc.publisher.department | Department of Pathology | en_US |
| dc.publisher.faculty | Faculty of Health Sciences | en_US |
| dc.rights.holder | The Author(s) | |
| dc.rights.uri | http://creativecommons.org/licenses/by-sa/4.0/ | en_US |
| dc.source | Malaria Journal | en_US |
| dc.source.journalissue | Article number: 421 | en_US |
| dc.source.journalvolume | 20 | en_US |
| dc.source.uri | https://malariajournal.biomedcentral.com/ | |
| dc.subject | Malaria | en_US |
| dc.subject | Drug resistance | en_US |
| dc.subject | Genomics | en_US |
| dc.subject | Multi-omics | en_US |
| dc.subject | Gene ontology | en_US |
| dc.subject | Protein–protein interaction | en_US |
| dc.title | Network-driven analysis of human–Plasmodium falciparum interactome: processes for malaria drug discovery and extracting in silico targets | en_US |
| dc.type | Journal Article | en_US |