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Bioinformatics Advance Access originally published online on February 21, 2006
Bioinformatics 2006 22(8):967-973; doi:10.1093/bioinformatics/btl042
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© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Assessing semantic similarity measures for the characterization of human regulatory pathways

Xiang Guo 1,*, Rongxiang Liu 2, Craig D. Shriver 3, Hai Hu 1 and Michael N. Liebman 1

1 Windber Research Institute Windber, PA 15963, USA
2 GlaxoSmithKline Pharmaceutical R&D King of Prussia, PA 19420, USA
3 Walter Reed Army Medical Center Washington, DC 20307, USA

*To whom correspondence should be addressed.

Motivation: Pathway modeling requires the integration of multiple data including prior knowledge. In this study, we quantitatively assess the application of Gene Ontology (GO)-derived similarity measures for the characterization of direct and indirect interactions within human regulatory pathways. The characterization would help the integration of prior pathway knowledge for the modeling.

Results: Our analysis indicates information content-based measures outperform graph structure-based measures for stratifying protein interactions. Measures in terms of GO biological process and molecular function annotations can be used alone or together for the validation of protein interactions involved in the pathways. However, GO cellular component-derived measures may not have the ability to separate true positives from noise. Furthermore, we demonstrate that the functional similarity of proteins within known regulatory pathways decays rapidly as the path length between two proteins increases. Several logistic regression models are built to estimate the confidence of both direct and indirect interactions within a pathway, which may be used to score putative pathways inferred from a scaffold of molecular interactions.

Contact: s.guo{at}wriwindber.org

Received on September 20, 2005; revised on January 16, 2006; accepted on February 3, 2006

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