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Nucleic Acids Res. 2014 Feb;42(3):1442-60. doi: 10.1093/nar/gkt938. Epub 2013 Oct 31.

Molecular mechanisms of system responses to novel stimuli are predictable from public data.

Author information

1
Seattle Biomedical Research Institute, Seattle, WA 98109-5219 USA, Institute for Systems Biology, Seattle, WA 98109-5240 USA, The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Science, Southeast University, Nanjing 210096, China and Department of Computer Science and Information Engineering, National Cheng Kung University, Tainan 704, Taiwan.

Abstract

Systems scale models provide the foundation for an effective iterative cycle between hypothesis generation, experiment and model refinement. Such models also enable predictions facilitating the understanding of biological complexity and the control of biological systems. Here, we demonstrate the reconstruction of a globally predictive gene regulatory model from public data: a model that can drive rational experiment design and reveal new regulatory mechanisms underlying responses to novel environments. Specifically, using ∼ 1500 publically available genome-wide transcriptome data sets from Saccharomyces cerevisiae, we have reconstructed an environment and gene regulatory influence network that accurately predicts regulatory mechanisms and gene expression changes on exposure of cells to completely novel environments. Focusing on transcriptional networks that induce peroxisomes biogenesis, the model-guided experiments allow us to expand a core regulatory network to include novel transcriptional influences and linkage across signaling and transcription. Thus, the approach and model provides a multi-scalar picture of gene dynamics and are powerful resources for exploiting extant data to rationally guide experimentation. The techniques outlined here are generally applicable to any biological system, which is especially important when experimental systems are challenging and samples are difficult and expensive to obtain-a common problem in laboratory animal and human studies.

PMID:
24185701
PMCID:
PMC3919619
DOI:
10.1093/nar/gkt938
[Indexed for MEDLINE]
Free PMC Article

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