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A Supervised Methodology for Analyzing Dysregulation in Splicing Machinery: An Application in Cancer Diagnosis

Deregulated splicing factors have shown to be associated with the development of several types of cancer and, therefore, the determination of such alterations can help the development of tumor-specific molecular targets for early prognosis and therapy. Determining the relevant splicing factors, however, is not a straightforward task mainly due to the heterogeneity of tumors and the variability across samples. In this work, a methodology based on supervised machine learning methods is proposed, allowing the determination of subsets of relevant factors that best discriminate samples. The methodology comprises three main phases: first, a ranking of splicing factors is determined by means of applying feature weighting algorithms; second, the best subset of factors that allows the induction of an accurate classifier is detected; then the confidence over the induced classifier is assessed by means of explaining the individual predictions. Finally, the utility and benefit of the proposed methodology are illustrated by means of analyzing a small dataset of neuroendocrine lung carcinoids, and the results showed that there exist small subsets of deregulated factors which can effectively distinguish between tumor samples and their respective adjacent non-tumor tissues.