Hagit Shatkay

Shixiao Liang, Aaron Higuera, Christina Peters et al.

This work proposes a domain-informed neural network architecture for experimental particle physics, using particle interaction localization with the time-projection chamber (TPC) technology for dark matter research as an example application. A key feature of the signals generated within the TPC is that they allow localization of particle interactions through a process called reconstruction. While multilayer perceptrons (MLPs) have emerged as a leading contender for reconstruction in TPCs, such a black-box approach does not reflect prior knowledge of the underlying scientific processes. This paper looks anew at neural network-based interaction localization and encodes prior detector knowledge, in terms of both signal characteristics and detector geometry, into the feature encoding and the output layers of a multilayer neural network. The resulting Domain-informed Neural Network (DiNN) limits the receptive fields of the neurons in the initial feature encoding layers in order to account for the spatially localized nature of the signals produced within the TPC. This aspect of the DiNN, which has similarities with the emerging area of graph neural networks in that the neurons in the initial layers only connect to a handful of neurons in their succeeding layer, significantly reduces the number of parameters in the network in comparison to an MLP. In addition, in order to account for the detector geometry, the output layers of the network are modified using two geometric transformations to ensure the DiNN produces localizations within the interior of the detector. The end result is a neural network architecture that has 60% fewer parameters than an MLP, but that still achieves similar localization performance and provides a path to future architectural developments with improved performance because of their ability to encode additional domain knowledge into the architecture.

Moumita Bhattacharya, Dai-Yin Lu, Shibani M Kudchadkar et al.

Clinical risk stratification for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HC) employs rules derived from American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines or the HCM Risk-SCD model (C-index of 0.69), which utilize a few clinical variables. We assessed whether data-driven machine learning methods that consider a wider range of variables can effectively identify HC patients with ventricular arrhythmias (VAr) that lead to SCD. We scanned the electronic health records of 711 HC patients for sustained ventricular tachycardia or ventricular fibrillation. Patients with ventricular tachycardia or ventricular fibrillation (n = 61) were tagged as VAr cases and the remaining (n = 650) as non-VAr. The 2-sample t test and information gain criterion were used to identify the most informative clinical variables that distinguish VAr from non-VAr; patient records were reduced to include only these variables. Data imbalance stemming from low number of VAr cases was addressed by applying a combination of over- and under-sampling strategies.We trained and tested multiple classifiers under this sampling approach, showing effective classification. We evaluated 93 clinical variables, of which 22 proved predictive of VAr. The ensemble of logistic regression and naive Bayes classifiers, trained based on these 22 variables and corrected for data imbalance, was most effective in separating VAr from non-VAr cases (sensitivity = 0.73, specificity = 0.76, C-index = 0.83). Our method (HCM-VAr-Risk Model) identified 12 new predictors of VAr, in addition to 10 established SCD predictors. In conclusion, this is the first application of machine learning for identifying HC patients with VAr, using clinical attributes.

Moumita Bhattacharya, Dai-Yin Lu, Ioannis Ventoulis et al.

Hypertrophic cardiomyopathy (HCM) patients have a high incidence of atrial fibrillation (AF) and increased stroke risk, even with low risk of congestive heart failure, hypertension, age, diabetes, previous stroke/transient ischemic attack scores. Hence, there is a need to understand the pathophysiology of AF and stroke in HCM. In this retrospective study, we develop and apply a data-driven, machine learning based method to identify AF cases, and clinical and imaging features associated with AF, using electronic health record data. HCM patients with documented paroxysmal/persistent/permanent AF (n = 191) were considered AF cases, and the remaining patients in sinus rhythm (n = 640) were tagged as No-AF. We evaluated 93 clinical variables and the most informative variables useful for distinguishing AF from No-AF cases were selected based on the 2-sample t test and the information gain criterion. We identified 18 highly informative variables that are positively (n = 11) and negatively (n = 7) correlated with AF in HCM. Next, patient records were represented via these 18 variables. Data imbalance resulting from the relatively low number of AF cases was addressed via a combination of oversampling and under-sampling strategies. We trained and tested multiple classifiers under this sampling approach, showing effective classification. Specifically, an ensemble of logistic regression and naive Bayes classifiers, trained based on the 18 variables and corrected for data imbalance, proved most effective for separating AF from No-AF cases (sensitivity = 0.74, specificity = 0.70, C-index = 0.80). Our model is the first machine learning based method for identification of AF cases in HCM. This model demonstrates good performance, addresses data imbalance, and suggests that AF is associated with a more severe cardiac HCM phenotype.

Moumita Bhattacharya, Claudine Jurkovitz, Hagit Shatkay

Patients associated with multiple co-occurring health conditions often face aggravated complications and less favorable outcomes. Co-occurring conditions are especially prevalent among individuals suffering from kidney disease, an increasingly widespread condition affecting 13% of the general population in the US. This study aims to identify and characterize patterns of co-occurring medical conditions in patients employing a probabilistic framework. Specifically, we apply topic modeling in a non-traditional way to find associations across SNOMEDCT codes assigned and recorded in the EHRs of>13,000 patients diagnosed with kidney disease. Unlike most prior work on topic modeling, we apply the method to codes rather than to natural language. Moreover, we quantitatively evaluate the topics, assessing their tightness and distinctiveness, and also assess the medical validity of our results. Our experiments show that each topic is succinctly characterized by a few highly probable and unique disease codes, indicating that the topics are tight. Furthermore, inter-topic distance between each pair of topics is typically high, illustrating distinctiveness. Last, most coded conditions grouped together within a topic, are indeed reported to co-occur in the medical literature. Notably, our results uncover a few indirect associations among conditions that have hitherto not been reported as correlated in the medical literature.

Moumita Bhattacharya, Claudine Jurkovitz, Hagit Shatkay

Multiple adverse health conditions co-occurring in a patient are typically associated with poor prognosis and increased office or hospital visits. Developing methods to identify patterns of co-occurring conditions can assist in diagnosis. Thus identifying patterns of associations among co-occurring conditions is of growing interest. In this paper, we report preliminary results from a data-driven study, in which we apply a machine learning method, namely, topic modeling, to electronic medical records, aiming to identify patterns of associated conditions. Specifically, we use the well established latent dirichlet allocation, a method based on the idea that documents can be modeled as a mixture of latent topics, where each topic is a distribution over words. In our study, we adapt the LDA model to identify latent topics in patients' EMRs. We evaluate the performance of our method both qualitatively, and show that the obtained topics indeed align well with distinct medical phenomena characterized by co-occurring conditions.

Moumita Bhattacharya, Deborah Ehrenthal, Hagit Shatkay

Obesity is one of the leading health concerns in the United States. Researchers and health care providers are interested in understanding factors affecting obesity and detecting the likelihood of obesity as early as possible. In this paper, we set out to recognize children who have higher risk of obesity by identifying distinct growth patterns in them. This is done by using clustering methods, which group together children who share similar body measurements over a period of time. The measurements characterizing children within the same cluster are plotted as a function of age. We refer to these plots as growthpattern curves. We show that distinct growth-pattern curves are associated with different clusters and thus can be used to separate children into the topmost (heaviest), middle, or bottom-most cluster based on early growth measurements.

Ramanuja Simha, Hagit Shatkay

Knowing the location of a protein within the cell is important for understanding its function, role in biological processes, and potential use as a drug target. Much progress has been made in developing computational methods that predict single locations for proteins, assuming that proteins localize to a single location. However, it has been shown that proteins localize to multiple locations. While a few recent systems have attempted to predict multiple locations of proteins, they typically treat locations as independent or capture inter-dependencies by treating each locations-combination present in the training set as an individual location-class. We present a new method and a preliminary system we have developed that directly incorporates inter-dependencies among locations into the multiple-location-prediction process, using a collection of Bayesian network classifiers. We evaluate our system on a dataset of single- and multi-localized proteins. Our results, obtained by incorporating inter-dependencies are significantly higher than those obtained by classifiers that do not use inter-dependencies. The performance of our system on multi-localized proteins is comparable to a top performing system (YLoc+), without restricting predictions to be based only on location-combinations present in the training set.

Hagit Shatkay

Hidden Markov models (HMMs) and partially observable Markov decision processes (POMDPs) form a useful tool for modeling dynamical systems. They are particularly useful for representing environments such as road networks and office buildings, which are typical for robot navigation and planning. The work presented here is concerned with acquiring such models. We demonstrate how domain-specific information and constraints can be incorporated into the statistical estimation process, greatly improving the learned models in terms of the model quality, the number of iterations required for convergence and robustness to reduction in the amount of available data. We present new initialization heuristics which can be used even when the data suffers from cumulative rotational error, new update rules for the model parameters, as an instance of generalized EM, and a strategy for enforcing complete geometrical consistency in the model. Experimental results demonstrate the effectiveness of our approach for both simulated and real robot data, in traditionally hard-to-learn environments.