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2014 ; 3
(1
): 39-51
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Comparative Analysis of Biologically Relevant Response Curves in Gene Expression
Experiments: Heteromorphy, Heterochrony, and Heterometry
#MMPMID27605029
Baker SG
Microarrays (Basel)
2014[Feb]; 3
(1
): 39-51
PMID27605029
show ga
To gain biological insights, investigators sometimes compare sequences of gene
expression measurements under two scenarios (such as two drugs or species). For
this situation, we developed an algorithm to fit, identify, and compare
biologically relevant response curves in terms of heteromorphy (different
curves), heterochrony (different transition times), and heterometry (different
magnitudes). The curves are flat, linear, sigmoid, hockey-stick (sigmoid missing
a steady state), transient (sigmoid missing two steady states), impulse (with
peak or trough), step (with intermediate-level plateau), impulse+ (impulse with
an extra parameter), step+ (step with an extra parameter), further characterized
by upward or downward trend. To reduce overfitting, we fit the curves to every
other response, evaluated the fit in the remaining responses, and identified the
most parsimonious curves that yielded a good fit. We measured goodness of fit
using a statistic comparable over different genes, namely the square root of the
mean squared prediction error as a percentage of the range of responses, which we
call the relative prediction error (RPE). We illustrated the algorithm using data
on gene expression at 14 times in the embryonic development in two species of
frogs. Software written in Mathematica is freely available.