Scheduled Seminars on 10/26/2010

YANG HUANG at 11:00  Edit  Reschedule  Delete

New method for detecting epistatic interactions uncovers interaction map of Plasmodium falciparum
Identification of epistatic interactions between genomic loci is fundamental for understanding genome organization and gene regulation. The increasing ease of generating highly resolved whole genome data potentially provides unprecedented access to these essential interactions. In the last decade, expression Quantitative Trait Loci (eQTL) studies have been widely used to determine the relation between single-locus genotype and gene expression variation. However, computational and statistical challenges have limited genome-wide studies of epistatic interactions affecting gene expression. We developed a new method for the reliable detection of epistatic interactions that overcomes severe statistical limitations of classical methods, allowing us to analyze such interactions on a genome-wide scale. We applied our approach to the human malaria parasite P. falciparum, an organism of enormous significance to human health. We also validated the approach using yeast eQTL dataset. In the landscape of epistatic interactions of this parasite, we found that interaction hotspot targets enriched for genes in the methyl-transfer pathway and involved in proteasome degradation, functions that highlight drug resistance and cellular stress response. Furthermore, epistatic loci encoded transcription factors involved in transcription complexes such as the ABC23 and ABC10 subunits of RNA polymerase II, suggesting direct regulatory impact of some hotspots. We also observed a correlation between elevated linkage disequilibrium (LD) between loci on different chromosomes and the number of target genes regulated jointly by these loci. Such results indicate LD’s important role in maintaining parasite specific, biological functions.

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