Chromosomal Spatial Correlation of Gene Expression in Plasmodium falciparum

Malaria is responsible for half a billion infections and two million deaths each year. Understanding the biology of Plasmodium falciparum is critical if effective vaccines are to be developed to fight against this aggressive parasite. New information about the regulatory mechanisms of P. falciparum promotes the elucidation of the fundamental metabolic and transcriptional pathways which we must understand to design vaccines and better treatments. Of particular importance is the intraerythrocytic development cycle (IDC), the part of the P. falciparum life cycle spent in the blood stream of host mammals and that is responsible for the physical symptoms of malaria. The goal of this investigation is to examine spatially dependent co-regulation of gene expression over the 48-hour IDC. Correlation between gene expression and gene location over a few genes demonstrates evidence of co-regulated genes or operons, while correlation over many genes may provide evidence for some other transcriptional regulation mechanism such as chromatin remodeling or enhancers. We develop and apply a visualization and statistical testing methodology to examine expression-location correlation in a time-course microarray study of the IDC transcriptome. Contrary to the current paucity of evidence, our findings show evidence for spatial correlation. The biological implications of detected blocks of moderate but consistent spatial correlation provide novel insights into the transcriptome of P. falciparum.