Incorporating topological information for predicting robust cancer subnetwork markers in human protein-protein interaction network

Autor: Navadon Khunlertgit, Byung-Jun Yoon
Rok vydání: 2016
Předmět:
0301 basic medicine
Computer science
Breast Neoplasms
Machine learning
computer.software_genre
Biochemistry
Topological information
Biological pathway
03 medical and health sciences
0302 clinical medicine
Discriminative model
Structural Biology
Protein Interaction Mapping
Gene expression
Message passing algorithm
Cluster Analysis
Humans
Protein Interaction Maps
Cluster analysis
Molecular Biology
Subnetwork
Translational bioinformatics
Subnetwork marker identification
Protein-protein interaction network
business.industry
Gene Expression Profiling
Applied Mathematics
Computational Biology
Cancer classification
Prognosis
Expression (mathematics)
3. Good health
Computer Science Applications
Gene Expression Regulation
Neoplastic

Identification (information)
Proceedings
030104 developmental biology
030220 oncology & carcinogenesis
Affinity propagation
Female
Artificial intelligence
DNA microarray
business
computer
Algorithms
Zdroj: BMC Bioinformatics
ISSN: 1471-2105
DOI: 10.1186/s12859-016-1224-1
Popis: Background Discovering robust markers for cancer prognosis based on gene expression data is an important yet challenging problem in translational bioinformatics. By integrating additional information in biological pathways or a protein-protein interaction (PPI) network, we can find better biomarkers that lead to more accurate and reproducible prognostic predictions. In fact, recent studies have shown that, “modular markers,” that integrate multiple genes with potential interactions can improve disease classification and also provide better understanding of the disease mechanisms. Results In this work, we propose a novel algorithm for finding robust and effective subnetwork markers that can accurately predict cancer prognosis. To simultaneously discover multiple synergistic subnetwork markers in a human PPI network, we build on our previous work that uses affinity propagation, an efficient clustering algorithm based on a message-passing scheme. Using affinity propagation, we identify potential subnetwork markers that consist of discriminative genes that display coherent expression patterns and whose protein products are closely located on the PPI network. Furthermore, we incorporate the topological information from the PPI network to evaluate the potential of a given set of proteins to be involved in a functional module. Primarily, we adopt widely made assumptions that densely connected subnetworks may likely be potential functional modules and that proteins that are not directly connected but interact with similar sets of other proteins may share similar functionalities. Conclusions Incorporating topological attributes based on these assumptions can enhance the prediction of potential subnetwork markers. We evaluate the performance of the proposed subnetwork marker identification method by performing classification experiments using multiple independent breast cancer gene expression datasets and PPI networks. We show that our method leads to the discovery of robust subnetwork markers that can improve cancer classification. Electronic supplementary material The online version of this article (doi:10.1186/s12859-016-1224-1) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE