4.7 Article

Fast network component analysis (FastNCA) for gene regulatory network reconstruction from microarray data

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Motivation: Recently developed network component analysis (NCA) approach is promising for gene regulatory network reconstruction from microarray data. The existing NCA algorithm is an iterative method which has two potential limitations: computational instability and multiple local solutions. The subsequently developed NCA-r algorithm with Tikhonov regularization can help solve the first issue but cannot completely handle the second one. Here we develop a novel Fast Network Component Analysis (FastNCA) algorithm which has an analytical solution that is much faster and does not have the above limitations. Results: Firstly FastNCA is compared to NCA and NCA-r using synthetic data. The reconstruction of FastNCA is more accurate than that of NCA-r and comparable to that of properly converged NCA. FastNCA is not sensitive to the correlation among the input signals, while its performance does degrade a little but not as dramatically as that of NCA. Like NCA, FastNCA is not very sensitive to small inaccuracies in a priori information on the network topology. FastNCA is about several tens times faster than NCA and several hundreds times faster than NCA-r. Then, the method is applied to real yeast cell-cycle microarray data. The activities of the estimated cell-cycle regulators by FastNCA and NCA-r are compared to the semi-quantitative results obtained independently by Lee et al. (2002). It is shown here that there is a greater agreement between the results of FastNCA and Lees, which is represented by the ratio 2333, than that between the results of NCA-r and Lees, which is 1433.

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