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Issue 5, 2012
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Symmetric Epistasis Estimation (SEE) and its application to dissecting interaction map of Plasmodium falciparum

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Abstract

It is being increasingly recognized that many important phenotypic traits, including various diseases, are governed by a combination of weak genetic effects and their interactions. While the detection of epistatic interactions that involve a non-additive effect of two loci on a quantitative trait is particularly challenging, this interaction type is fundamental for the understanding of genome organization and gene regulation. However, current methods that detect epistatic interactions typically rely on the existence of a strong primary effect, considerably limiting the sensitivity of the search. To fill this gap, we developed a new method, SEE (Symmetric Epistasis Estimation), allowing the genome-wide detection of epistatic interactions without the need for a strong primary effect. We applied our approach to progeny crosses of the human malaria parasite P. falciparum and S. cerevisiae. We found an abundance of epistatic interactions in the parasite and a much smaller number of such interactions in yeast. The genome of P. falciparum also harboured several epistatic interaction hotspots that putatively play a role in drug resistance mechanisms. The abundance of observed epistatic interactions might suggest a mechanism of compensation for the extremely limited repertoire of transcription factors. Interestingly, epistatic interaction hotspots were associated with elevated levels of linkage disequilibrium, an observation that suggests selection pressure acting on P. falciparum, potentially reflecting host-pathogen interactions or drug-induced selection.

Graphical abstract: Symmetric Epistasis Estimation (SEE) and its application to dissecting interaction map of Plasmodium falciparum

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Publication details

The article was received on 12 Aug 2011, accepted on 23 Dec 2011 and first published on 15 Mar 2012


Article type: Paper
DOI: 10.1039/C2MB05333K
Citation: Mol. BioSyst., 2012,8, 1544-1552
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    Symmetric Epistasis Estimation (SEE) and its application to dissecting interaction map of Plasmodium falciparum

    Y. Huang, G. Siwo, S. Wuchty, M. T. Ferdig and T. M. Przytycka, Mol. BioSyst., 2012, 8, 1544
    DOI: 10.1039/C2MB05333K

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