Deep Mining from Omics Data.

Since the advent of high-throughput omics technologies, various molecular data such as genes, transcripts, proteins, and metabolites have been made widely available to researchers. This has afforded clinicians, bioinformaticians, statisticians, and data scientists the opportunity to apply their innovations in feature mining and predictive modeling to a rich data resource to develop a wide range of generalizable prediction models. What has become apparent over the last 10 years is that researchers have adopted deep neural networks (or "deep nets") as their preferred paradigm of choice for complex data modeling due to the superiority of performance over more traditional statistical machine learning approaches, such as support vector machines. A key stumbling block, however, is that deep nets inherently lack transparency and are considered to be a "black box" approach. This naturally makes it very difficult for clinicians and other stakeholders to trust their deep learning models even though the model predictions appear to be highly accurate. In this chapter, we therefore provide a detailed summary of the deep net architectures typically used in omics research, together with a comprehensive summary of the notable "deep feature mining" techniques researchers have applied to open up this black box and provide some insights into the salient input features and why these models behave as they do. We group these techniques into the following three categories: (a) hidden layer visualization and interpretation; (b) input feature importance and impact evaluation; and (c) output layer gradient analysis. While we find that omics researchers have made some considerable gains in opening up the black box through interpretation of the hidden layer weights and node activations to identify salient input features, we highlight other approaches for omics researchers, such as employing deconvolutional network-based approaches and development of bespoke attribute impact measures to enable researchers to better understand the relationships between the input data and hidden layer representations formed and thus the output behavior of their deep nets.