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    Estimation of the proteomic cancer co-expression sub networks by using association estimators
    (Public Library Science, 2017) Erdoğan, Cihat; Kurt, Zeyneb; Diri, Banu
    In this study, the association estimators, which have significant influences on the gene network inference methods and used for determining the molecular interactions, were examined within the co-expression network inference concept. By using the proteomic data from five different cancer types, the hub genes/proteins within the disease-associated gene-gene/protein-protein interaction sub networks were identified. Proteomic data from various cancer types is collected from The Cancer Proteome Atlas (TCPA). Correlation and mutual information (MI) based nine association estimators that are commonly used in the literature, were compared in this study. As the gold standard to measure the association estimators' performance, a multi-layer data integration platform on gene-disease associations (DisGeNET) and the Molecular Signatures Database (MSigDB) was used. Fisher's exact test was used to evaluate the performance of the association estimators by comparing the created co-expression networks with the disease-associated pathways. It was observed that the MI based estimators provided more successful results than the Pearson and Spearman correlation approaches, which are used in the estimation of biological networks in the weighted correlation network analysis (WGCNA) package. In correlation-based methods, the best average success rate for five cancer types was 60%, while in MI-based methods the average success ratio was 71% for James-Stein Shrinkage (Shrink) and 64% for Schurmann-Grassberger (SG) association estimator, respectively. Moreover, the hub genes and the inferred sub networks are presented for the consideration of researchers and experimentalists.
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    Investigation of Association Estimators in Network Inference Algorithms on Breast Cancer Proteomic Data
    (IEEE, 2017) Erdoğan, Cihat; Kurt, Zeyneb; Diri, Banu
    In this study, association estimators applied in the network inference methods used to determine disease-related molecular interactions using breast cancer, which is the most common type of cancer in women, proteomic data were examined and hub genes in the gene-gene interaction network related to the disease were identified. Proteomic data of 901 breast cancer patients were generated using reverse phase protein array provided by The Cancer Proteome Atlas (TCPA) as a data set. Correlations and mutual information (MI) based estimators used in the literature were compared in the study, and WGCNA and minet R packages were used. As a result, it is seen that the MI based shrink estimator method has more successful results than the correlation-based adjacency function used in the estimation of biological networks in the WGCNA package. Achievement rates have ranged from 0.67 to 1.00 in the shrink estimation, with adjacency functions ranging from 0.33 to 0.86 for different module counts. In addition, hub genes and inferenced networks of successful results arc presented for the review of biologists.