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Presentation Details
| Drosophila Melanogaster Potential Model for Thrombosis Fakiha Siddiqui1, Syed Mohammad Omer Khalid2, Nusrat Jabeen3, Mushtaq Hussain4, Jawed Fareed1. 1Department of Pathology and Laboratory Medicine, Health Science Division, Loyola University Chicago, Chicago, IL.2Dow University of Health Science, Karachi.3Department of Microbiology, University of Karachi, Karachi.4Dow Fly Lab and Stock Center, Dow College of Biotechnology, Dow University of Health Sciences, Karachi |
Abstract
Thrombosis is one of the major hematological and/or cardiovascular anomalies resulting into 25% death annually exclusively and inclusively with other ailments. Studying the biology of the disease requires animal models and, in this regards, different vertebrate species have been exploited. In the present study, we aim to find suitability of Drosophila melanogaster as a model for thrombosis pathobiology and platform for the drug screening using systems biology approaches. Briefly out of 74 of the candidate human genes linked with thrombosis, 57 (77%) were found orthologues to D. melanogaster genes. The interactomes share considerable similarity in the modular architecture. Gene ontogeny analysis showed that interactomes of both human and D. melanogaster are involved in KEGG pathway (ECM receptor interaction); molecular function including serine-type endopeptidase inhibitor activity, serine-type endopeptidase activity, calcium binding, integrin binding, heme binding, and cell adhesion molecule binding; biological process includes proteolysis, cell matrix adhesion, and cell adhesion; and cellular component particularly extracellular matrix interactions. Based on centrality, 15 and 12 hub genes were identified in the human and D. melanogaster respectively, which shares 86% and 40% orthology with total interactome and hub genes of D. melanogaster, respectively (Figure 1). Importantly, these molecules also showed noticeable structural homology further suggesting similar functionality. To see the potential of D. melanogaster as an antithrombotic drug screening platform, important drug targets like VKORC1, factor X and factor II (thrombin) were screened against the fruit fly genome. Interestingly, ortholgues of all were found in D. melanogaster with substantial structural similarities and showed binding with known inhibitors. In summary, our findings suggest that D. melanogaster could be exploited as a drug screening platform for anti-thrombotic drugs.
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