PIMKL: Pathway Induced Multiple Kernel Learning
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Reliable identification of molecular biomarkers is essential for accurate patient stratification. While state-of-the-art machine learning approaches for sample classification continue to push boundaries in terms of performance, most of these methods are not able to integrate different data types and lack generalization power limiting their application in a clinical setting. Furthermore, many methods behave as black boxes, therefore we have very little understanding about the mechanisms that lead to the prediction provided. While opaqueness concerning machine behaviour might not be a problem in deterministic domains, in health care, providing explanations about the molecular factors and phenotypes that are driving the classification is crucial to build trust in the performance of the predictive system. We propose Pathway Induced Multiple Kernel Learning (PIMKL), a novel methodology to classify samples reliably that can, at the same time, provide a pathway-based molecular fingerprint of the signature that underlies the classification. PIMKL exploits prior knowledge in the form of molecular interaction networks and annotated gene sets, by optimizing a mixture of pathway-induced kernels using a Multiple Kernel Learning algorithm (MKL), an approach that has demonstrated excellent performance in different machine learning applications. After optimizing the combination of kernels for prediction of a specific phenotype, the model provides a stable molecular signature that can be interpreted in the light of the ingested prior knowledge and that can be used in transfer learning tasks.
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