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Integrating protein annotations for the in silico prioritization of putative drug target proteins in malaria
Dissertation (MSc)--University of Pretoria, 2012.
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University of Pretoria
2013
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| _version_ | 1867613483770576896 |
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| access_status_str | Open Access |
| author2 | Joubert, Fourie |
| author_browse | Joubert, Fourie |
| author_facet | Joubert, Fourie |
| collection | Thesis |
| dc_rights_str_mv | © 2012 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria |
| description | Dissertation (MSc)--University of Pretoria, 2012. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/24715 |
| institution | University of Pretoria (South Africa) |
| last_indexed | 2026-06-10T12:36:52.413Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2013 |
| publishDateRange | 2013 |
| publishDateSort | 2013 |
| publisher | University of Pretoria |
| publisherStr | University of Pretoria |
| record_format | dspace |
| source_str | UPSpace — University of Pretoria Institutional Repository |
| spelling | oai:repository.up.ac.za:2263/24715 Integrating protein annotations for the in silico prioritization of putative drug target proteins in malaria Joubert, Fourie pmpangase@gmail.com Mpangase, Phelelani Thokozani Anti-malarial drugs Plasmodium parasites H. sapiens A. gambiae Protein sequences UCTD Dissertation (MSc)--University of Pretoria, 2012. Current anti-malarial methods have been effective in reducing the number of malarial cases. However, these methods do not completely block the transmission of the parasite. Research has shown that repeated use of the current anti-malarial drugs, which include artemisinin-based drug combinations, might be toxic to humans. There have also been reports of an emergence of artemisinin-resistant parasites. Finding anti-malarial drugs through the drug discovery process takes a long time and failure results in a great financial loss. The failure of drug discovery projects can be partly attributed to the improper selection of drug targets. There is thus a need for an eff ective way of identifying and validating new potential malaria drug targets for entry into the drug discovery process. The availability of the genome sequences for the Plasmodium parasite, human host and the Anopheles mosquito vector has facilitated post-genomic studies on malaria. Proper utilizationof this data, in combination with computational biology and bioinformatics techniques, could aid in the in silico prioritization of drug targets. This study was aimed at extensively annotating the protein sequences from the Plasmodium parasites, H. sapiens and A. gambiae with data from di fferent online databases in order to create a resource for the prioritization of drug targets in malaria. Essentiality, assay feasibility, resistance, toxicity, structural information and druggability were the main target selection criteria which were used to collect data for protein annotations. The data was used to populate the Discovery resource (http://malport. bi.up.ac.za/) for the in silico prioritization of potential drug targets. A new version of the Discovery system, Discovery 2.0 (http://discovery.bi.up.ac.za/), has been developed using Java. The system contains new and automatically updated data as well as improved functionalities. The new data in Discovery 2.0 includes UniProt accessions, gene ontology annotations from the UniProt-GOA project, pathways from Reactome and Malaria Parasite Metabolic Pathways databases, protein-protein interactions data from. IntAct as well as druggability data from the DrugEBIlity resource hosted by ChEMBL. Users can access the data by searching with a protein identi er, UniProt accession, protein name or through the advanced search which lets users filter protein sequences based on different protein properties. The results are organized in a tabbed environment, with each tab displaying different protein annotation data. A sample investigation using a previously proposed malarial target, S-adenosyl-Lhomocysteine hydrolase, was carried out to demonstrate the diff erent categories of data available in Discovery 2.0 as well as to test if the available data is su fficient for assessment and prioritization of drug targets. The study showed that using the annotation data in Discovery 2.0, a protein can be assessed, in a species comparative manner, on the potential of being a drug target based on the selection criteria mentioned here. However, supporting data from literature is also needed to further validate the findings. Biochemistry unrestricted 2013-09-06T18:11:34Z 2013-05-24 2013-09-06T18:11:34Z 2013-04-12 2012 2013-05-15 Dissertation Mpangase, PT 2012, Integrating protein annotations for the in silico prioritization of putative drug target proteins in malaria, MSc dissertation, University of Pretoria, Pretoria, viewed yymmdd < http://hdl.handle.net/2263/24715 > E13/4/463/gm http://hdl.handle.net/2263/24715 http://upetd.up.ac.za/thesis/available/etd-05152013-120636/ © 2012 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria application/pdf University of Pretoria |
| spellingShingle | Anti-malarial drugs Plasmodium parasites H. sapiens A. gambiae Protein sequences UCTD Integrating protein annotations for the in silico prioritization of putative drug target proteins in malaria |
| title | Integrating protein annotations for the in silico prioritization of putative drug target proteins in malaria |
| title_full | Integrating protein annotations for the in silico prioritization of putative drug target proteins in malaria |
| title_fullStr | Integrating protein annotations for the in silico prioritization of putative drug target proteins in malaria |
| title_full_unstemmed | Integrating protein annotations for the in silico prioritization of putative drug target proteins in malaria |
| title_short | Integrating protein annotations for the in silico prioritization of putative drug target proteins in malaria |
| title_sort | integrating protein annotations for the in silico prioritization of putative drug target proteins in malaria |
| topic | Anti-malarial drugs Plasmodium parasites H. sapiens A. gambiae Protein sequences UCTD |
| url | http://hdl.handle.net/2263/24715 http://upetd.up.ac.za/thesis/available/etd-05152013-120636/ |