Deep Learning for Proteomics Data for Feature Selection and Classification

Abstract

Todays high-throughput molecular profiling technologies allow to routinely create large datasets providing detailed information about a given biological sample, e.g. about the concentrations of thousands contained proteins. A standard task in the context of precision medicine is to identify a set of biomarkers (e.g. proteins) from these datasets that can be used for disease diagnosis, prognosis or to monitor treatment response. However, finding good biomarker sets is still a challenging task due to the high dimensionality and complexity of the data and the often quite high noise level. In this work, we present an approach to this problem based on Deep Neural Networks (DNN) and a transfer learning strategy using simulation data. To allow interpretation of the results, we compare different approaches to analyze the learned DNN. Based on these interpretation approaches, we describe how to extract biomarker sets. Comparison of our method to a state-of-the-art L1-SVM approach shows that the new approach is able to find better biomarker sets for classification when small sets are desired. Compared to a state-of-the-art 1support vector machine ( 1-SVM) approach, our method achieves better results for the classification task when a small number of features are needed.

An Interpretable Deep Learning Approach for Biomarker Detection in LC-MS Proteomics Data

“…Despite the current successful approaches, most of these studies are empirically driven, and are lacking a justifiable interpretation foundation [26]. Moreover, as machine learning (ML) and DL have been rapidly growing also for realworld applications, a concern has emerged that the high precision accuracy may not be enough in practice [27].…”

“…However, permutation analysis is not computationally feasible for high-throughput LC-MS analysis. Among three other interpretation categories the out-performances of attribution analysis has been demonstrated in [26] on MALDI-TOF MS data. In this study, therefore, one of the methods in attribution category called layer-wise relevance propagation (LRP) [32] is employed for interpretation of the model predictions of LC-MS proteomics.…”