Turbocharging Matched Molecular Pair Analysis: Optimizing the Identification and Analysis of Pairs

We
have applied the two most commonly used methods for automatic
matched pair identification, obtained the optimum settings, and discovered
that the two methods are synergistic. A turbocharging approach to
matched pair analysis is advocated in which a first round (a conservative
categorical approach that uses an analogy with coin flips, heads corresponding
to an increase in a measured property, tails to a decrease, and a
biased coin to a structural change that reliably causes a change in
that property) provides the settings for a second round (which uses
the magnitude of the change in properties). Increased chemical specificity
allows reliable knowledge to be extracted from smaller sets of pairs,
and an assay-specific upper limit can be placed on the number of pairs
required before adequate sampling of variability has been achieved.