Assessing semantic similarity measures for the characterization of human regulatory pathways

Xiang Guo*, Rongxiang Liu, Craig D. Shriver, Hai Hu, Michael N. Liebman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

154 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)967-973
Number of pages7
JournalBioinformatics
Volume22
Issue number8
DOIs
StatePublished - Apr 2006
Externally publishedYes

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