Computational analysis of functionally related genes in mouse response to Plasmodium chabaudi

According to the World Health Organization (WHO), over 1-3 million children under the age of five die due to malaria each year. The aim of this project is to increase our understanding of the Plasmodium chabaudi parasite and of its interactions with the mammalian host using a computational approach. This is achieved by applying a time-series clustering algorithm to a publicly available short time-series gene expression data representing two disease states (P. chabaudi infected and non infected), two genders (male and female), two protocols (intact and gonadectomized), and four time points (0, 3, 7, and 14 days after inoculation) of Mus musculus (mouse) response to P. chabaudi infection. Results obtained provide a rigorous statistical explanation to the fact that intact males were more likely than intact females to die following P. chabaudi infection on one hand, and on the other hand, gonadectomy of male and female mice altered these sex-associated differences. These findings may suggest that sex steroid hormone modulates immune responses to pathogen attacks.

[1]  I. Androulakis,et al.  Analysis of time-series gene expression data: methods, challenges, and opportunities. , 2007, Annual review of biomedical engineering.

[2]  S. Hay,et al.  The global distribution of clinical episodes of Plasmodium falciparum malaria , 2005, Nature.

[3]  A. Holder,et al.  Malaria vaccines. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[4]  D. Conway,et al.  Efficacy of RTS,S/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomised trial , 2001, The Lancet.

[5]  The Plasmodium genome database Designing and mining a eukaryotic genomics resource , .

[6]  Tomoaki Tamaki,et al.  Sequence of Plasmodium falciparum chromosome 12 , 2002, Nature.

[7]  G. Coatney,et al.  Malaria therapy. , 1970, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[8]  J. Reeder,et al.  Malaria vaccines , 2002, The Medical journal of Australia.

[9]  S. Falkow,et al.  Cag pathogenicity island-specific responses of gastric epithelial cells to Helicobacter pylori infection , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[10]  W. Weidanz,et al.  Immunity to Plasmodium chabaudi adami in the B-cell-deficient mouse , 1981, Nature.

[11]  Jonathan E. Allen,et al.  Sequence of Plasmodium falciparum chromosomes 2, 10, 11 and 14 , 2002, Nature.

[12]  Kwang-Hyun Cho,et al.  Microarray data clustering based on temporal variation: FCV with TSD preclustering. , 2003, Applied bioinformatics.

[13]  Alexander Schliep,et al.  Using hidden Markov models to analyze gene expression time course data , 2003, ISMB.

[14]  E V Koonin,et al.  Chromosome 2 sequence of the human malaria parasite Plasmodium falciparum. , 1998, Science.

[15]  Shyamal D. Peddada,et al.  Gene Selection and Clustering for Time-course and Dose-response Microarray Experiments Using Order-restricted Inference , 2003, Bioinform..

[16]  X. Su,et al.  Malaria: therapy, genes and vaccines. , 2006, Current molecular medicine.

[17]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[18]  Ziv Bar-Joseph,et al.  Clustering short time series gene expression data , 2005, ISMB.

[19]  F. Jørgensen,et al.  Towards an understanding of drug resistance in malaria: three-dimensional structure of Plasmodium falciparum dihydrofolate reductase by homology building. , 1999, Bioorganic & medicinal chemistry.

[20]  M. Alpers,et al.  The malaria vaccine development program in Papua New Guinea. , 2003, Trends in parasitology.

[21]  Jonathan E. Allen,et al.  Genome sequence of the human malaria parasite Plasmodium falciparum , 2002, Nature.

[22]  R. Gwilliam,et al.  Sequence of Plasmodium falciparum chromosomes 1, 3–9 and 13 , 2002, Nature.

[23]  Paola Sebastiani,et al.  Cluster analysis of gene expression dynamics , 2002, Proceedings of the National Academy of Sciences of the United States of America.