TF-Cluster: a pipeline for identifying functionally coordinated transcription factors via network decomposition of the shared coexpression connectivity matrix (SCCM).

BMC Syst Biol (2011) PMID 21496241

Identifying the key transcription factors (TFs) controlling a biological process is the first step toward a better understanding of underpinning regulatory mechanisms. However, due to the involvement of a large number of genes and complex interactions in gene regulatory networks, identifying TFs involved in a biological process remains particularly difficult. The challenges include: (1) Most eukaryotic genomes encode thousands of TFs, which are organized in gene families of various sizes and in many cases with poor sequence conservation, making it difficult to recognize TFs for a biological process; (2) Transcription usually involves several hundred genes that generate a combination of intrinsic noise from upstream signaling networks and lead to fluctuations in transcription; (3) A TF can function in different cell types or developmental stages. Currently, the methods available for identifying TFs involved in biological processes are still very scarce, and the development of novel, more powerful methods is desperately needed.