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Open Access Research article

A new computational approach redefines the subtelomeric vir superfamily of Plasmodium vivax

Francisco Javier Lopez13, Maria Bernabeu1, Carmen Fernandez-Becerra1 and Hernando A del Portillo124*

Author Affiliations

1 Barcelona Centre for International Health Research, (CRESIB, Hospital Clínic-Universitat de Barcelona), Roselló 153, 1a planta (CEK building), 08036, Barcelona, Spain

2 Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain

3 Present address: Andalusian Human Genome Sequencing Centre (CASEGH) Medical Genome Project (MGP) INSUR Building, Albert Einstein Street Cartuja 93 Scientific and Technology Park, 41092, Sevilla, Spain

4 ICREA Barcelona Centre for International Health Research, (CRESIB, Hospital Clínic-Universitat de Barcelona), Barcelona, Spain

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BMC Genomics 2013, 14:8  doi:10.1186/1471-2164-14-8

Published: 16 January 2013

Abstract

Background

Subtelomeric multigene families of malaria parasites encode virulent determinants. The published genome sequence of Plasmodium vivax revealed the largest subtelomeric multigene family of human malaria parasites, the vir super-family, presently composed of 346 vir genes subdivided into 12 different subfamilies based on sequence homologies detected by BLAST.

Results

A novel computational approach was used to redefine vir genes. First, a protein-weighted graph was built based on BLAST alignments. This graph was processed to ensure that edge weights are not exclusively based on the BLAST score between the two corresponding proteins, but strongly dependant on their graph neighbours and their associations. Then the Markov Clustering Algorithm was applied to the protein graph. Next, the Homology Block concept was used to further validate this clustering approach. Finally, proteome-wide analysis was carried out to predict new VIR members. Results showed that (i) three previous subfamilies cannot longer be classified as vir genes; (ii) most previously unclustered vir genes were clustered into vir subfamilies; (iii) 39 hypothetical proteins were predicted as VIR proteins; (iv) many of these findings are supported by a number of structural and functional evidences, sub-cellular localization studies, gene expression analysis and chromosome localization (v) this approach can be used to study other multigene families in malaria.

Conclusions

This methodology, resource and new classification of vir genes will contribute to a new structural framing of this multigene family and other multigene families of malaria parasites, facilitating the design of experiments to understand their role in pathology, which in turn may help furthering vaccine development.

Keywords:
Malaria; Plasmodium vivax; vir genes; VIR proteins; Subtelomeric multigene families; Sequence clustering; Similarity networks; Homology blocks