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This work studies the reconstruction of gene regulatory networks by the means of network component analysis (NCA). We will expound a family of convex optimization-based methods for estimating the transcription factor control strengths and the transcription factor activities (TFAs). The approach taken in this work is to decompose the problem into a network connectivity strength estimation phase and a transcription factor activity estimation phase. In the control strength estimation phase, we formulate a new subspace-based method incorporating a choice of multiple error metrics. For the source estimation phase we propose a total least squares (TLS) formulation that generalizes many existing methods. Both estimation procedures are noniterative and yield the optimal estimates according to various proposed error metrics. We test the performance of the proposed algorithms on simulated data and experimental gene expression data for the yeast Saccharomyces cerevisiae and demonstrate that the proposed algorithms have superior effectiveness in comparison with both Bayesian Decomposition (BD) and our previous FastNCA approach, while the computational complexity is still orders of magnitude less than BD.
Computational Biology and Bioinformatics, IEEE/ACM Transactions on (Volume:9 , Issue: 5 )
Date of Publication: Sept.-Oct. 2012