Send to:

Choose Destination
See comment in PubMed Commons below
PLoS One. 2012;7(7):e41854. doi: 10.1371/journal.pone.0041854. Epub 2012 Jul 25.

Identifying responsive modules by mathematical programming: an application to budding yeast cell cycle.

Author information

  • 1Key Laboratory of Systems Biology, SIBS-Novo Nordisk Translational Research Centre for PreDiabetes, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.


High-throughput biological data offer an unprecedented opportunity to fully characterize biological processes. However, how to extract meaningful biological information from these datasets is a significant challenge. Recently, pathway-based analysis has gained much progress in identifying biomarkers for some phenotypes. Nevertheless, these so-called pathway-based methods are mainly individual-gene-based or molecule-complex-based analyses. In this paper, we developed a novel module-based method to reveal causal or dependent relations between network modules and biological phenotypes by integrating both gene expression data and protein-protein interaction network. Specifically, we first formulated the identification problem of the responsive modules underlying biological phenotypes as a mathematical programming model by exploiting phenotype difference, which can also be viewed as a multi-classification problem. Then, we applied it to study cell-cycle process of budding yeast from microarray data based on our biological experiments, and identified important phenotype- and transition-based responsive modules for different stages of cell-cycle process. The resulting responsive modules provide new insight into the regulation mechanisms of cell-cycle process from a network viewpoint. Moreover, the identification of transition modules provides a new way to study dynamical processes at a functional module level. In particular, we found that the dysfunction of a well-known module and two new modules may directly result in cell cycle arresting at S phase. In addition to our biological experiments, the identified responsive modules were also validated by two independent datasets on budding yeast cell cycle.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk