k- Strong Inference Algorithm: A Hybrid Information Theory Based Gene Network Inference Algorithm.

Gene networks allow researchers to understand the underlying mechanisms between diseases and genes while reducing the need for wet lab experiments. Numerous gene network inference (GNI) algorithms have been presented in the literature to infer accurate gene networks. We proposed a hybrid GNI algorithm, k-Strong Inference Algorithm (ksia), to infer more reliable and robust gene networks from omics datasets. To increase reliability, ksia integrates Pearson correlation coefficient (PCC) and Spearman rank correlation coefficient (SCC) scores to determine mutual information scores between molecules to increase diversity of relation predictions. To infer a more robust gene network, ksia applies three different elimination steps to remove redundant and spurious relations between genes. The performance of ksia was evaluated on microbe microarrays database in the overlap analysis with other GNI algorithms, namely ARACNE, C3NET, CLR, and MRNET. Ksia inferred less number of relations due to its strict elimination steps. However, ksia generally performed better on Escherichia coli (E.coli) and Saccharomyces cerevisiae (yeast) gene expression datasets due to F- measure and precision values. The integration of association estimator scores and three elimination stages slightly increases the performance of ksia based gene networks. Users can access ksia R package and user manual of package via https://github.com/ozgurcingiz/ksia .

The Performance Comparison of Gene Co-expression Networks of Breast and Prostate Cancer using Different Selection Criteria.

Gene co-expression networks (GCN) present undirected relations between genes to understand molecular structures behind the diseases, including cancer. The utilization of various biological datasets and gene network inference (GNI) algorithms can reveal meaningful gene-gene interactions of GCNs. This study applies three GNI algorithms on mRNA gene expression, RNA-Seq, and miRNA-target genes datasets to infer GCNs of breast and prostate cancers. To evaluate the performance of the GCNs, we utilize overlap analysis via literature data, topological assessment, and Gene Ontology-based biological assessment. The results emphasize how the selection of biological datasets and GNI algorithms affect the performance results on different evaluation criteria. GCNs on microarray gene expression data slightly outperform in overlap analysis. Also, GCNs on RNA-Seq and gene expression datasets follow scale-free topology. The biological assessment results are close to each other on all biological datasets. C3NET algorithm-based GCNs did not contain any biological assessment modules; therefore, it is not optimal for biological assessment. GNI algorithms' selection did not change the overlap analysis and topological assessment results. Our primary objective is to compare the performance results of biological datasets and GNI algorithms based on different evaluation criteria. For this purpose, we developed the GNIAP R package that enables users to select different GNI algorithms to infer GCNs. The GNIAP R package also provides literature-based overlap analysis, and topological and biological analyses on GCNs. Users can access the GNIAP R package via https://github.com/ozgurcingiz/GNIAP .

Two-tier combinatorial structure to integrate various gene co-expression networks of prostate cancer.

Advances in DNA sequencing technologies enable researchers to integrate various biological datasets in order to reveal hidden relations at the molecular level. In this study, we present a two-tiered combinatorial structure (TTCS) to integrate gene co-expression networks (GCNs) that are inferred from microarray gene expression, RNA-Seq and miRNA-target gene data. In the initial phase of TTCS, we derive GCNs by using gene network inference (GNI) algorithms for each dataset. In the first and second integration phases, we use straightforward methods: intersection, union and simple majority voting to combine GCNs. We use overlap, topological and biological analyses in performance evaluation and investigate the integration effects of GCNs separately for all phases. Our results prove that the first integration phase has limited contribution on performance. However, combining the biological datasets in the second phase significantly enhances the overlap and topological performance analyses.