TY - JOUR
T1 - Reconstruction of transcriptional regulatory networks by stability-based network component analysis
AU - Chen, Xi
AU - Xuan, Jianhua
AU - Wang, Chen
AU - Shajahan, Ayesha N.
AU - Riggins, Rebecca B.
AU - Clarke, Robert
PY - 2013/11
Y1 - 2013/11
N2 - Reliable inference of transcription regulatory networks is a challenging task in computational biology. Network component analysis (NCA) has become a powerful scheme to uncover regulatory networks behind complex biological processes. However, the performance of NCA is impaired by the high rate of false connections in binding information. In this paper, we integrate stability analysis with NCA to form a novel scheme, namely stability-based NCA (sNCA), for regulatory network identification. The method mainly addresses the inconsistency between gene expression data and binding motif information. Small perturbations are introduced to prior regulatory network, and the distance among multiple estimated transcript factor (TF) activities is computed to reflect the stability for each TF's binding network. For target gene identification, multivariate regression and t-statistic are used to calculate the significance for each TF-gene connection. Simulation studies are conducted and the experimental results show that sNCA can achieve an improved and robust performance in TF identification as compared to NCA. The approach for target gene identification is also demonstrated to be suitable for identifying true connections between TFs and their target genes. Furthermore, we have successfully applied sNCA to breast cancer data to uncover the role of TFs in regulating endocrine resistance in breast cancer.
AB - Reliable inference of transcription regulatory networks is a challenging task in computational biology. Network component analysis (NCA) has become a powerful scheme to uncover regulatory networks behind complex biological processes. However, the performance of NCA is impaired by the high rate of false connections in binding information. In this paper, we integrate stability analysis with NCA to form a novel scheme, namely stability-based NCA (sNCA), for regulatory network identification. The method mainly addresses the inconsistency between gene expression data and binding motif information. Small perturbations are introduced to prior regulatory network, and the distance among multiple estimated transcript factor (TF) activities is computed to reflect the stability for each TF's binding network. For target gene identification, multivariate regression and t-statistic are used to calculate the significance for each TF-gene connection. Simulation studies are conducted and the experimental results show that sNCA can achieve an improved and robust performance in TF identification as compared to NCA. The approach for target gene identification is also demonstrated to be suitable for identifying true connections between TFs and their target genes. Furthermore, we have successfully applied sNCA to breast cancer data to uncover the role of TFs in regulating endocrine resistance in breast cancer.
KW - Multivariate regression
KW - Network component analysis
KW - Stability analysis
KW - Transcriptional regulatory network
KW - t-statistic
UR - http://www.scopus.com/inward/record.url?scp=84894581929&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84894581929&partnerID=8YFLogxK
U2 - 10.1109/TCBB.2012.146
DO - 10.1109/TCBB.2012.146
M3 - Article
C2 - 24407294
AN - SCOPUS:84894581929
SN - 1545-5963
VL - 10
SP - 1347
EP - 1358
JO - IEEE/ACM Transactions on Computational Biology and Bioinformatics
JF - IEEE/ACM Transactions on Computational Biology and Bioinformatics
IS - 6
M1 - 6365177
ER -