国田 勝行

This paper deals with an input/output signal recovery problem for nonlinear multiple-input single-output autoregressive exogenous (ARX) models with input nonlinearity, which are used in data-driven systems biology. A matrix rank minimization approach is applied, and a new signal recovery algorithm for nonlinear ARX models is provided. The proposed algorithm recovers output signals and nonlinear-transformed input signals on a linear subspace using some assumptions about nonlinear functions and does not require the exact knowledge of nonlinear functions. Numerical examples using experimental data of signal transduction of cellular systems show the efficiency of the proposed algorithm.

Secretion of insulin transiently increases after eating, resulting in a high circulating concentration. Fasting limits insulin secretion, resulting in a low concentration of insulin in the circulation. We analyzed transcriptional responses to different temporal patterns and doses of insulin in the hepatoma FAO cells and identified 13 up-regulated and 16 down-regulated insulin-responsive genes (IRGs). The up-regulated IRGs responded more rapidly than did the down-regulated IRGs to transient stepwise or pulsatile increases in insulin concentration, whereas the down-regulated IRGs were repressed at lower concentrations of insulin than those required to stimulate the up-regulated IRGs. Mathematical modeling of the insulin response as two stages-(i) insulin signaling to transcription and (ii) transcription and mRNA stability-indicated that the first stage was the more rapid stage for the down-regulated IRGs, whereas the second stage of transcription was the more rapid stage for the up-regulated IRGs. A subset of the IRGs that were up-regulated or down-regulated in the FAO cells was similarly regulated in the livers of rats injected with a single dose of insulin. Thus, not only can cells respond to insulin but they can also interpret the intensity and pattern of signal to produce distinct transcriptional responses. These results provide insight that may be useful in treating obesity and type 2 diabetes associated with aberrant insulin production or tissue responsiveness.