Naim U. Rashid

David K. Lim, Naim U. Rashid, Junier B. Oliva et al.

Deep Learning (DL) methods have dramatically increased in popularity in recent years. While its initial success was demonstrated in the classification and manipulation of image data, there has been significant growth in the application of DL methods to problems in the biomedical sciences. However, the greater prevalence and complexity of missing data in biomedical datasets present significant challenges for DL methods. Here, we provide a formal treatment of missing data in the context of Variational Autoencoders (VAEs), a popular unsupervised DL architecture commonly utilized for dimension reduction, imputation, and learning latent representations of complex data. We propose a new VAE architecture, NIMIWAE, that is one of the first to flexibly account for both ignorable and non-ignorable patterns of missingness in input features at training time. Following training, samples can be drawn from the approximate posterior distribution of the missing data can be used for multiple imputation, facilitating downstream analyses on high dimensional incomplete datasets. We demonstrate through statistical simulation that our method outperforms existing approaches for unsupervised learning tasks and imputation accuracy. We conclude with a case study of an EHR dataset pertaining to 12,000 ICU patients containing a large number of diagnostic measurements and clinical outcomes, where many features are only partially observed.

Naim U. Rashid, Daniel J. Luckett, Jingxiang Chen et al.

The complexity of human cancer often results in significant heterogeneity in response to treatment. Precision medicine offers potential to improve patient outcomes by leveraging this heterogeneity. Individualized treatment rules (ITRs) formalize precision medicine as maps from the patient covariate space into the space of allowable treatments. The optimal ITR is that which maximizes the mean of a clinical outcome in a population of interest. Patient-derived xenograft (PDX) studies permit the evaluation of multiple treatments within a single tumor and thus are ideally suited for estimating optimal ITRs. PDX data are characterized by correlated outcomes, a high-dimensional feature space, and a large number of treatments. Existing methods for estimating optimal ITRs do not take advantage of the unique structure of PDX data or handle the associated challenges well. In this paper, we explore machine learning methods for estimating optimal ITRs from PDX data. We analyze data from a large PDX study to identify biomarkers that are informative for developing personalized treatment recommendations in multiple cancers. We estimate optimal ITRs using regression-based approaches such as Q-learning and direct search methods such as outcome weighted learning. Finally, we implement a superlearner approach to combine a set of estimated ITRs and show that the resulting ITR performs better than any of the input ITRs, mitigating uncertainty regarding user choice of any particular ITR estimation methodology. Our results indicate that PDX data are a valuable resource for developing individualized treatment strategies in oncology.