Leveraging existing biological knowledge in the identification of candidate genes for facial dysmorphology.
BACKGROUND
In response to the frequently overwhelming output of high-throughput microarray experiments, we propose a methodology to facilitate interpretation of biological data in the context of existing knowledge. Through the probabilistic integration of explicit and implicit data sources a functional interaction network can be constructed. Each edge connecting two proteins is weighted by a confidence value capturing the strength and reliability of support for that interaction given the combined data sources. The resulting network is examined in conjunction with expression data to identify groups of genes with significant temporal or tissue specific patterns. In contrast to unstructured gene lists, these networks often represent coherent functional groupings.


RESULTS
By linking from shared functional categorizations to primary biological resources we apply this method to craniofacial microarray data, generating biologically testable hypotheses and identifying candidate genes for craniofacial development.


CONCLUSIONS
The novel methodology presented here illustrates how the effective integration of pre-existing biological knowledge and high-throughput experimental data drives biological discovery and hypothesis generation.
Tipney
Hannah J
HJ
Computational Pharmacology Department, University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA. hannah.tipney@uchsc.edu
Leach
Sonia M
SM
Feng
Weiguo
W
Spritz
Richard
R
Williams
Trevor
T
Hunter
Lawrence
L
D000465:Algorithms; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000378:metabolism; D030541:Databases, Genetic; D020869:Gene Expression Profiling / Q000379:methods; D053263:Gene Regulatory Networks; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010363:Pattern Recognition, Automated