Title: Seed-weighted random walk ranking for cancer biomarker prioritisation: a case study in leukaemia

Authors: Tianxiao Huan; Xiaogang Wu; Zengliang Bai; Jake Y. Chen

Addresses: Life Science School, Shandong University, Shandong, JN 250100 China ' School of Informatics, Indiana University, Indianapolis, IN 46202 USA; Center for Systems Biology and Personalized Medicine, Indianapolis, IN 46202 USA ' Life Science School, Shandong University, Shandong, JN 250100 China ' School of Informatics, Indiana University, Indianapolis, IN 46202 USA; Center for Systems Biology and Personalized Medicine, Indianapolis, IN 46202 USA

Abstract: A central focus of clinical proteomics for cancer is to identify protein biomarkers with diagnostic and therapeutic application potential. Network-based analyses have been used in computational disease-related gene prioritisation for several years. The Random Walk Ranking (RWR) algorithm has been successfully applied to prioritising disease-related gene candidates by exploiting global network topology in a Protein-Protein Interaction (PPI) network. Increasing the specificity and sensitivity of biomarkers may require consideration of similar or closely-related disease phenotypes and molecular pathological mechanisms shared across different disease phenotypes. In this paper, we propose a method called Seed-Weighted Random Walk Ranking (SW-RWR) for prioritizing cancer biomarker candidates. This method uses the information of cancer phenotype association to assign to each gene a disease-specific, weighted value to guide the RWR algorithm in a global human PPI network. In a case study of prioritizing leukaemia biomarkers, SW-RWR outperformed a typical local network-based analysis in coverage and also showed better accuracy and sensitivity than the original RWR method (global network-based analysis). Our results suggest that the tight correlation among different cancer phenotypes could play an important role in cancer biomarker discovery.

Keywords: cancer biomarkers; PPI; protein-protein interaction; disease association networks; random walk ranking; leukaemia biomarkers; bioinformatics; biomarker prioritisation; clinical proteomics; protein biomarkers; cancer phenotypes; biomarker discovery.

DOI: 10.1504/IJDMB.2014.059064

International Journal of Data Mining and Bioinformatics, 2014 Vol.9 No.2, pp.135 - 148

Received: 17 Feb 2012
Accepted: 02 Mar 2012
Published online: 21 Oct 2014 *

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