Correlation Between Computed Equilibrium Secondary Structure Free Energy and siRNA Efficiency
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The strongest trend is a positive linear (r 2 = 0.87) correlation between ln(remaining mRNA) and â Gms , the combined free energy cost of unraveling the siRNA and creating the break in the mRNA secondary structure at the complementary target strand region. At the same time, the free energy change â Gtotal of the entire process mRNA + siRNA â (mRNA â siRNA)complex is not correlated with RNAi efficiency, even after averaging. These general findings appear to be robust to details of the computational protocols. The correlation be- tween computed â Gms and experimentally observed RNAi efficiency can be used to enhance the ability of a machine learning algorithm based on a support vector machine (SVM) to predict effective siRNA sequences for a given target mRNA. Specifically, we observe modest, 3 to 7%, but consistent improvement in the positive predictive value (PPV) when the SVM training set is pre- or post-filtered according to a â Gms threshold.
- Masters Theses