title: Network Biomarkers Constructed from Gene Expression and Protein-Protein Interaction Data for Accurate Prediction of Leukemia.
abstract: Leukemia is a leading cause of cancer deaths in the developed countries. Great efforts have been undertaken in search of diagnostic biomarkers of leukemia. However, leukemia is highly complex and heterogeneous, involving interaction among multiple molecular components. Individual molecules are not necessarily sensitive diagnostic indicators. Network biomarkers are considered to outperform individual molecules in disease characterization. We applied an integrative approach that identifies active network modules as putative biomarkers for leukemia diagnosis. We first reconstructed the leukemia-specific PPI network using protein-protein interactions from the Protein Interaction Network Analysis (PINA) and protein annotations from GeneGo. The network was further integrated with gene expression profiles to identify active modules with leukemia relevance. Finally, the candidate network-based biomarker was evaluated for the diagnosing performance. A network of 97 genes and 400 interactions was identified for accurate diagnosis of leukemia. Functional enrichment analysis revealed that the network biomarkers were enriched in pathways in cancer. The network biomarkers could discriminate leukemia samples from the normal controls more effectively than the known biomarkers. The network biomarkers provide a useful tool to diagnose leukemia and also aids in further understanding the molecular basis of leukemia.
authors.affiliation: Center for Systems Biology, Soochow University, Suzhou, 215006, China.
authors.forename: Xuye
authors.initials: X
authors.lastname: Yuan
authors.affiliation: School of Chemistry and Biological Engineering, Suzhou University of Science and Technology, Suzhou, 215011, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Center for Systems Biology, Soochow University, Suzhou, 215006, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Center for Systems Biology, Soochow University, Suzhou, 215006, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pediatrics, The First People's Hospital of Lianyungang, Lianyungang, 222002, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Xu
authors.affiliation: Key Laboratory of Systems Biology, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Luonan
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Hematology, The Third Hospital Affiliated to Nantong University, No. 585 North Xingyuan Road, Wuxi, Jiangsu214041, China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Hua
authors.affiliation: Center for Systems Biology, Soochow University, Suzhou, 215006, China.
authors.forename: Bairong
authors.initials: B
authors.lastname: Shen
keywords: integrative analysis; leukemia.; network biomarker