Data-Driven Modeling For Decision Support Systems And Treatment Management In Personalized Healthcare

Massive amount of electronic medical records (EMRs) accumulating from patients and populations motivates clinicians and data scientists to collaborate for the advanced analytics to create knowledge that is essential to address the extensive personalized insights needed for patients, clinicians, providers, scientists, and health policy makers. Learning from large and complicated data is using extensively in marketing and commercial enterprises to generate personalized recommendations. Recently the medical research community focuses to take the benefits of big data analytic approaches and moves to personalized (precision) medicine. So, it is a significant period in healthcare and medicine for transferring to a new paradigm. There is a noticeable opportunity to implement a learning health care system and data-driven healthcare to make better medical decisions, better personalized predictions; and more precise discovering of risk factors and their interactions. In this research we focus on data-driven approaches for personalized medicine. We propose a research framework which emphasizes on three main phases: 1) Predictive modeling, 2) Patient subgroup analysis and 3) Treatment recommendation. Our goal is to develop novel methods for each phase and apply them in real-world applications. In the fist phase, we develop a new predictive approach based on feature representation using deep feature learning and word embedding techniques. Our method uses different deep architectures (Stacked autoencoders, Deep belief network and Variational autoencoders) for feature representation in higher-level abstractions to obtain effective and more robust features from EMRs, and then build prediction models on the top of them. Our approach is particularly useful when the unlabeled data is abundant whereas labeled one is scarce. We investigate the performance of representation learning through a supervised approach. We perform our method on different small and large datasets. Finally we provide a comparative study and show that our predictive approach leads to better results in comparison with others. In the second phase, we propose a novel patient subgroup detection method, called Supervised Biclustring (SUBIC) using convex optimization and apply our approach to detect patient subgroups and prioritize risk factors for hypertension (HTN) in a vulnerable demographic subgroup (African-American). Our approach not only finds patient subgroups with guidance of a clinically relevant target variable but also identifies and prioritizes risk factors by pursuing sparsity of the input variables and encouraging similarity among the input variables and between the input and target variables. Finally, in the third phase, we introduce a new survival analysis framework using deep learning and active learning with a novel sampling strategy. First, our approach provides better representation with lower dimensions from clinical features using labeled (time-to-event) and unlabeled (censored) instances and then actively trains the survival model by labeling the censored data using an oracle. As a clinical assistive tool, we propose a simple yet effective treatment recommendation approach based on our survival model. In the experimental study, we apply our approach on SEER-Medicare data related to prostate cancer among African-Americans and white patients. The results indicate that our approach outperforms significantly than baseline models

Bayesian Approaches For Modeling Variation

A core focus of statistics is determining how much of the variation in data may be attributed to the signal of interest, and how much to noise. When the sources of variation are many and complex, a Bayesian approach to data analysis offers a number of advantages. In this thesis, we propose and implement new Bayesian methods for modeling variation in two general settings. The first setting is high-dimensional linear regression where the unknown error variance is also of interest. Here, we show that a commonly used class of conjugate shrinkage priors can lead to underestimation of the error variance. We then extend the Spike-and-Slab Lasso (SSL, Rockova and George, 2018) to the unknown variance case, using an alternative, independent prior framework. This extended procedure outperforms both the fixed variance approach and alternative penalized likelihood methods on both simulated and real data. For the second setting, we move from univariate response data where the predictors are known, to multivariate response data in which potential predictors are unobserved. In this setting, we first consider the problem of biclustering, where a motivating example is to find subsets of genes which have similar expression in a subset of patients. For this task, we propose a new biclustering method called Spike-and-Slab Lasso Biclustering (SSLB). SSLB utilizes the SSL prior to find a doubly-sparse factorization of the data matrix via a fast EM algorithm. Applied to both a microarray dataset and a single-cell RNA-sequencing dataset, SSLB recovers biologically meaningful signal in the data. The second problem we consider in this setting is nonlinear factor analysis. The goal here is to find low-dimensional, unobserved ``factors\u27\u27 which drive the variation in the high-dimensional observed data in a potentially nonlinear fashion. For this purpose, we develop factor analysis BART (faBART), an MCMC algorithm which alternates sampling from the posterior of (a) the factors and (b) a functional approximation to the mapping from the factors to the data. The latter step utilizes Bayesian Additive Regression Trees (BART, Chipman et al., 2010). On a variety of simulation settings, we demonstrate that with only the observed data as the input, faBART is able to recover both the unobserved factors and the nonlinear mapping

Bayesian correlated clustering to integrate multiple datasets

Motivation: The integration of multiple datasets remains a key challenge in systems biology and genomic medicine. Modern high-throughput technologies generate a broad array of different data types, providing distinct – but often complementary – information. We present a Bayesian method for the unsupervised integrative modelling of multiple datasets, which we refer to as MDI (Multiple Dataset Integration). MDI can integrate information from a wide range of different datasets and data types simultaneously (including the ability to model time series data explicitly using Gaussian processes). Each dataset is modelled using a Dirichlet-multinomial allocation (DMA) mixture model, with dependencies between these models captured via parameters that describe the agreement among the datasets. Results: Using a set of 6 artificially constructed time series datasets, we show that MDI is able to integrate a significant number of datasets simultaneously, and that it successfully captures the underlying structural similarity between the datasets. We also analyse a variety of real S. cerevisiae datasets. In the 2-dataset case, we show that MDI’s performance is comparable to the present state of the art. We then move beyond the capabilities of current approaches and integrate gene expression, ChIP-chip and protein-protein interaction data, to identify a set of protein complexes for which genes are co-regulated during the cell cycle. Comparisons to other unsupervised data integration techniques – as well as to non-integrative approaches – demonstrate that MDI is very competitive, while also providing information that would be difficult or impossible to extract using other methods