Tianwei Yu

Tianwei Yu

In the integrative analyses of omics data, it is often of interest to extract data representation from one data type that best reflect its relations with another data type. This task is traditionally fulfilled by linear methods such as canonical correlation analysis (CCA) and partial least squares (PLS). However, information contained in one data type pertaining to the other data type may be complex and in nonlinear form. Deep learning provides a convenient alternative to extract low-dimensional nonlinear data embedding. In addition, the deep learning setup can naturally incorporate the effects of clinical confounding factors into the integrative analysis. Here we report a deep learning setup, named Autoencoder-based Integrative Multi-omics data Embedding (AIME), to extract data representation for omics data integrative analysis. The method can adjust for confounder variables, achieve informative data embedding, rank features in terms of their contributions, and find pairs of features from the two data types that are related to each other through the data embedding. In simulation studies, the method was highly effective in the extraction of major contributing features between data types. Using a real microRNA-gene expression dataset, and a real DNA methylation-gene expression dataset, we show that AIME excluded the influence of confounders including batch effects, and extracted biologically plausible novel information. The R package based on Keras and the TensorFlow backend is available at https://github.com/tianwei-yu/AIME.

Yunchuan Kong, Tianwei Yu

Gene expression data represents a unique challenge in predictive model building, because of the small number of samples $(n)$ compared to the huge amount of features $(p)$. This "$n<<p$" property has hampered application of deep learning techniques for disease outcome classification. Sparse learning by incorporating external gene network information could be a potential solution to this issue. Still, the problem is very challenging because (1) there are tens of thousands of features and only hundreds of training samples, (2) the scale-free structure of the gene network is unfriendly to the setup of convolutional neural networks. To address these issues and build a robust classification model, we propose the Graph-Embedded Deep Feedforward Networks (GEDFN), to integrate external relational information of features into the deep neural network architecture. The method is able to achieve sparse connection between network layers to prevent overfitting. To validate the method's capability, we conducted both simulation experiments and a real data analysis using a breast cancer RNA-seq dataset from The Cancer Genome Atlas (TCGA). The resulting high classification accuracy and easily interpretable feature selection results suggest the method is a useful addition to the current classification models and feature selection procedures. The method is available at https://github.com/yunchuankong/NetworkNeuralNetwork.

Yunchuan Kong, Tianwei Yu

A unique challenge in predictive model building for omics data has been the small number of samples $(n)$ versus the large amount of features $(p)$. This "$n\ll p$" property brings difficulties for disease outcome classification using deep learning techniques. Sparse learning by incorporating external gene network information such as the graph-embedded deep feedforward network (GEDFN) model has been a solution to this issue. However, such methods require an existing feature graph, and potential mis-specification of the feature graph can be harmful on classification and feature selection. To address this limitation and develop a robust classification model without relying on external knowledge, we propose a \underline{for}est \underline{g}raph-\underline{e}mbedded deep feedforward \underline{net}work (forgeNet) model, to integrate the GEDFN architecture with a forest feature graph extractor, so that the feature graph can be learned in a supervised manner and specifically constructed for a given prediction task. To validate the method's capability, we experimented the forgeNet model with both synthetic and real datasets. The resulting high classification accuracy suggests that the method is a valuable addition to sparse deep learning models for omics data.

Tianwei Yu

We present a method of variable selection for the sparse generalized additive model. The method doesn't assume any specific functional form, and can select from a large number of candidates. It takes the form of incremental forward stagewise regression. Given no functional form is assumed, we devised an approach termed roughening to adjust the residuals in the iterations. In simulations, we show the new method is competitive against popular machine learning approaches. We also demonstrate its performance using some real datasets. The method is available as a part of the nlnet package on CRAN https://cran.r-project.org/package=nlnet.