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International Biometric Society
SIMULATING GENE SILENCING THROUGH INTERVENTION ANALYSIS
V.Djordjilovic1, M.Chiogna1, S.Massa2, C.Romualdi3
1Department
of Statistical Sciences, University of Padua,
of Statistics, Oxford University,
3Department of Biology, University of Padua.
2Department
Gene silencing is the most straightforward and reliable experimental technique for
studying gene function. It consists of lowering the expression of the targeted gene in
controlled, experimental conditions. By observing consequences of such an
intervention scientists can verify existing hypothesis and form new ones about the
role of that particular gene, both in terms of phenotype and the expression levels of
other genes. Although very advantageous, gene silencing has a number of
limitations pertaining, in particular, to the technical aspect and cost of the
experiment. We propose a method for investigation of potential effects of silencing,
before physically performing an experiment. This should allow a more efficient
design and organization of the experiment and considerable savings in terms of time
and money. The statistical components of this approach comprise a statistical
model for the set of genes of interest for the biologists (including the one to be
silenced) and data on expression levels of such genes. In the first step we combine
available biological knowledge with gene expression data to build a probabilistic
directed acyclic graphical model that represents the joint distribution of the set of
genes. This model then represents the basis for the so-called intervention analysis,
which aims to predict the effect of changing the marginal distribution of the targeted
gene on the remaining genes. The issue of quality of gene expression data is
crucial, as reliability of results highly depends on good estimation of the model. The
statistical approach also requires some preliminary hypothesis to be discussed with
biologists, in order to evaluate their validity in the context at hand.
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International Biometric Conference, Florence, ITALY, 6 – 11 July 2014