Using mechanistic Bayesian networks to identify downstream targets of the sonic hedgehog pathway.
BACKGROUND
The topology of a biological pathway provides clues as to how a pathway operates, but rationally using this topology information with observed gene expression data remains a challenge.


RESULTS
We introduce a new general-purpose analytic method called Mechanistic Bayesian Networks (MBNs) that allows for the integration of gene expression data and known constraints within a signal or regulatory pathway to predict new downstream pathway targets. The MBN framework is implemented in an open-source Bayesian network learning package, the Python Environment for Bayesian Learning (PEBL). We demonstrate how MBNs can be used by modeling the early steps of the sonic hedgehog pathway using gene expression data from different developmental stages and genetic backgrounds in mouse. Using the MBN approach we are able to automatically identify many of the known downstream targets of the hedgehog pathway such as Gas1 and Gli1, along with a short list of likely targets such as Mig12.


CONCLUSIONS
The MBN approach shown here can easily be extended to other pathways and data types to yield a more mechanistic framework for learning genetic regulatory models.
Shah
Abhik
A
Bioinformatics Program, University of Michigan, Ann Arbor, MI 48109, USA. shahad@umich.edu
Tenzen
Toyoaki
T
McMahon
Andrew P
AP
Woolf
Peter J
PJ
D001499:Bayes Theorem; D019295:Computational Biology / Q000379:methods*; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D053823:Hedgehog Proteins / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D015398:Signal Transduction
D053823:Hedgehog Proteins