Title
Identification of regulatory modules by co-clustering latent variable models: stem cell differentiation.
Abstract
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.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.
Year
DOI
Venue
2006
10.1093/bioinformatics/btl343
Bioinformatics
Keywords
Field
DocType
kr supplementary information,major stem cell species,stem cell biology,stem cell differentiation,lvm-based method,stem cell cluster,cell type-specific transcription factor,specific cell type,co-clustering latent variable model,cell subpopulations,regulatory module,genome sequence,gene regulation,stem cell,transcription factor,latent variable model
Gene,Stem cell,Biology,Latent variable model,Cellular differentiation,Cell type,Cell,Bioinformatics,E2F,Transcription factor
Journal
Volume
Issue
ISSN
22
16
1367-4811
Citations 
PageRank 
References 
11
0.98
8
Authors
4
Name
Order
Citations
PageRank
Je-Gun Joung11489.99
Dong-ho Shin2344.98
Rho Hyun Seong3110.98
Byoung-Tak Zhang41571158.56