Identification of regulatory modules by co-clustering latent variable models: stem cell differentiation.
BACKGROUND
An important issue in stem cell biology is to understand how to direct differentiation towards a specific cell type. To elucidate the mechanism, previous studies have focused on identifying the responsible gene regulators, which have, however, failed to provide a systemic view of regulatory modules. To obtain a unified description of the regulatory modules, we characterized major stem cell species by employing a co-clustering latent variable model (LVM). The LVM-based method allowed us to elucidate the cell type-specific transcription factors, using genomic sequences as well as expression profiles.


RESULTS
We used a list of genes enriched in each of 21 stem cell subpopulations, and their upstream genomic sequences. The LVM-based study allowed us to uncover the regulatory modules for each stem cell cluster, e.g. GABP and E2F for the proliferation phase, and Ap2alpha and Ap2gamma for the quiescence phase. Furthermore, the identities of the stem cell clusters were well revealed by the constituent genes that were directly targeted by the modules. Consequently, our analytical framework was demonstrated to be useful through a detailed case study of stem cell differentiation and can be applied to problems with similar characteristics.
Joung
Je-Gun
JG
Center for Bioinformation Technology, Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742, Republic of Korea.
Shin
Dongho
D
Seong
Rho Hyun
RH
Zhang
Byoung-Tak
BT
D000465:Algorithms; D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D020869:Gene Expression Profiling; D016678:Genome; D006801:Humans; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D010363:Pattern Recognition, Automated; D013234:Stem Cells / Q000166:cytology*