PlasmoDB is database that contains functional genomes of various Plasmodium species, one of the highly researched parasites. Plasmodium is an apicomplexan parasite that causes various medically important diseases in animal and man, including malaria. PlasmoDB is housed under EuPathDb (Eukaryotic Pathogens Database Resource), which is a part of the National Institute of Health funded-Bioinformatics Resource Consortium (BRC) initiative.
History & ResourcesEdit
The first version of PlasmoDB was released in 2000 by researchers at University of Pennsylvania with funding from Burroughs Wellcome Fund . This was as a result of sequence and annotation data generated for the P. falciparum 3D7 genome . Over the years, as research in the field moved ahead, the database grew much larger. PlasmoDB incorporated sequences from different strains of Plasmodium , linked computational data with experimental information like microarray results and protein expression profile for different stages of parasites , included information about evolation of the parasite, it's cellular localization, bioinformatic tools, links to other useful sites like KEGG (database), PubMed (database), to name a few . The latest version number 9.3 released on 10 March 2013 contains details on the metabolic pathways and chemical compounds that inhibit molecules in these pathways with links to the experimental details for these results.
How It WorksEditAs discussed above, PlasmoDB today has myriad resources available on the website, and the video on this page demonstrates the use of 7] found that P. falciparum was more sensitive than human cells to inhibitors of unfolded protein response (UPR) and endoplasmic-reticulum-associated protein degradation (ERAD). The authors hypothesized that the Plasmodium has limited UPR and ERAD pathways when compared to human cells. To prove this hypothesis they made use of the resources avaliable at the PlasmoDB website. Slideshow from figure’s 1a to 1f demonstrate an example for one of the methods used in the paper, which is explained as follows:
• Using NCBI’s (National Center for Biotechnology Information) protein database search for a human protein involved in the UPR/ERAD pathway, signal peptide peptidase (SPP) taken as an example here (Figure 1a).
• Select the ‘FASTA’ option highlighted in blue, which is a link to the FASTA sequence of the protein. Copy the sequence to use in PlasmoDB BLASTA search (Figure 1b).
• On the PlasmoDB homepage, under the ‘Search Genes by:’ heading select the ‘Similarity/Pattern’. You should not be able to see and select the BLAST search tool (Figure 1c).
• Under ‘Target data type’ choose ‘Proteins’, ‘BLAST Program’ select ‘blastp’, ‘Target Organism’ select ‘Plasmodium falciparum’, strain ‘Plasmodium falciparum 3D7’. Insert the copied FASTA sequence of human SPP protein in the ‘Input Sequence’ box and select the BLAST search options based on your requirement. In the paper, Harbut et al. set the E-value to 0.00001, which was also the value used for this search (Figure 1d).• Figures 1e and 1f show the results obtained for this query. Indeed P. falciparum does have a homologous gene for the human SPP and this gene is present on chromosome 14 (genome results).
Similarly, searches were done for other homologous proteins of human UPR and ERAD in P. falciparum. These results show that P. falciparum lacks the transcriptional regulation machinery present in humans and only has the translational machinery and hence has a lower 50% inhibitory concentration (IC50) for the ERAD and UPR drugs than human cells (summarized in Figure 2).
1. PlasmoDB: An integrative database of the Plasmodium falciparum genome. Tools for accessing and analyzing finished and unfinished sequence data. The Plasmodium Genome Database Collaborative. Nucleic Acids Res, 2001. 29(1): p. 66-9. [PubMed]
2. Fletcher, C., The Plasmodium falciparum Genome Project. Parasitol Today, 1998. 14(9): p. 342-4. [PubMed]
3. Bahl, A., et al., PlasmoDB: the Plasmodium genome resource. An integrated database providing tools for accessing, analyzing and mapping expression and sequence data (both finished and unfinished). Nucleic Acids Res, 2002. 30(1): p. 87-90. [PubMed]
4. Bahl, A., et al., PlasmoDB: the Plasmodium genome resource. A database integrating experimental and computational data. Nucleic Acids Res, 2003. 31(1): p. 212-5.[PubMed.]
5. Stoeckert C.J. Jr., et al., PlasmoDB v5: new looks, new genomes. Trends Parasitol, 2006. 22(12): p. 543-6. [Pubmed]
6. Aurrecoechea, C., et al., PlasmoDB: a functional genomic database for malaria parasites. Nucleic Acids Res, 2009. 37(Database issue): p. D539-43. [PubMed]
7. Harbut, M.B., et al., Targeting the ERAD pathway via inhibition of signal peptide peptidase for antiparasitic therapeutic design. Proc Natl Acad Sci U S A, 2012. 109(52): p. 21486-91. [PubMed]