For target compound analysis, a flow injection analysis (FIA) was carried out to determine the fragmentor setting to improve the compound response.
Stimulus-response curves were recorded by increasing the stimulus intensity until the maximal compound response amplitude was obtained.
Second, a polymorphism that affects compound response may be linked to a different polymorphism that affects gene expression.
The stimulus threshold was defined as the stimulus intensity (mA) required to produce a compound response 50% of maximal amplitude.
It should be noted that we predicted compound response from steady-state mRNA expression levels not only when inheritance of both compound response and expression levels is Mendelian, but also in cases when inheritance of both compound response and expression levels is genetically complex.
With this mathematical model we next sought to distinguish between synergy and antagonism of compound response curves derived from high-throughput screening efforts (Fig. 1C).
First, a polymorphism may affect both gene expression and compound response independently (pleiotropy), with the expression levels providing a read-out of the inheritance at the locus.
The only difference observed in the experiment shown in Fig. 2C was that the medium-sized compound response was larger when the soma membrane was active than when it was passive regardless of the soma conductance weighting factor.
Expression may sometimes be a better predictor of compound response than genotype because expression can integrate many genetic changes, and may therefore reflect the overall physiological state of the cell rather than just the effect of one locus.
On the other hand, expression may be a poorer predictor of compound response than genotype in cases when transcript levels of untreated cells is uncorrelated to transcript levels of drug-treated cells.
We compared compound response measurements from 3D cultures versus those obtained from 2D cultures.
