Chromosomal Clustering of Periodically Expressed Genes in Plasmodium falciparum

Identification of periodically expressed genes (PEGs) has been widely studied, but understanding how PEGs are distributed along chromosomes is largely unexplored. In this study we investigated chromosomal clusters of PEGs in stages of intraerythrocytic developmental cycle (IDC) of Plasmodium falciparum using the cDNA microarray data provided by the organizers of the Critical Assessment of Microarray Data Analysis (CAMDA) 2004 competition. To this end, we implemented an analysis consisting of three stages: first, fitting sinusoidal curves to the 46 time points to identify periodically expressed oligonucleoitides, second, using a support vector machine (SVM) to assign the periodically expressed oligonucleoitides to the four known developmental stages of the IDC, and third, defining stage-specific physically adjacent clusters and evaluating through permutation whether there were more clusters than expected by chance. We identified 2949 periodically expressed oligonucleoitides (2204 genes) where periodicity explained at least 70% of the variation over time, and 718, 624, 141, and 167 genes were assigned to the ring/early trophozoite, trophozoite/early schizont, schizont, and early ring stages, respectively, with at least 80% probability for stage prediction. Finally, we identified 312 clusters of two or more adjacent genes assigned to the same stage. Using a permutation-based method, we found that we observed more clusters of size five than expected by chance (p = 0.04). There was also a suggestion (p ∼ 0.10) of more clusters than expected for other cluster sizes. Our findings suggest that the expression of periodically expressed genes may be coordinated locally on chromosomes where there are clusters of genes within same stage, suggesting cis-regulation.