Rosas Rubio, Juan F.

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    Biological signaling pathways and potential mathematical network representations: Biological discovery through optimization
    (2015) Rosas Rubio, Juan F.; Cabrera Ríos, Mauricio; College of Engineering; Dávila, Saylisse; Seguel, Jaime; Department of Industrial Engineering; Acuña Fernández, Edgar
    Establishing the role that different genes play in the development of cancer is a daunting task. A step towards this end is the detection of genes that are important in the illness from high-throughput biological experiments. Furthermore, it is safe to say that even with a list of potentially important genes it is highly unlikely that these show expression changes independently. A biological signaling pathway is a more plausible underlying mechanism as favored in the literature. This thesis attempts to build a mathematical network problem through the analysis of microarray experiments. A pre-selection of genes is carried out with a multiple criteria optimization framework previously published by our research group [1]. Afterwards, network optimization methods Traveling Salesperson Problem and Minimum Spanning Tree are proposed to identify potential signaling pathways via the most correlated path among the genes of interest. A case study with lung cancer was conducted where our methodology identified 11 potential biomarkers genes and optimal pathway solutions maximizing correlations between them. Additionally a meta-analysis was undertaken for lung cancer obtaining several gene relationships that may play a key role when smoking habits are taken in consideration. Biological evidencing is provided to assess the effectiveness of the proposed methods.