Longitudinal patient data has the potential to improve clinical risk stratification models for disease. However, chronic diseases that progress slowly over time are often heterogeneous in their clinical presentation. Patients may progress through disease stages at varying rates. This leads to pathophysiological misalignment over time, making it difficult to consistently compare patients in a clinically meaningful way. Furthermore, patients present clinically for the first time at different stages of disease. This eliminates the possibility of simply aligning patients based on their initial presentation. Finally, patient data may be sampled at different rates due to differences in schedules or missed visits. To address these challenges, we propose a robust measure of patient similarity based on subsequence alignment. Compared to global alignment techniques that do not account for pathophysiological misalignment, focusing on the most relevant subsequences allows for an accurate measure of similarity between patients. We demonstrate the utility of our approach in settings where longitudinal data, while useful, are limited and lack a clear temporal alignment for comparison. Applied to the task of stratifying patients for risk of progression to probable Alzheimer's Disease, our approach outperforms models that use only snapshot data (AUROC of 0.839 vs. 0.812) and models that use global alignment techniques (AUROC of 0.822). Our results support the hypothesis that patients' trajectories are useful for quantifying inter-patient similarities and that using subsequence matching and can help account for heterogeneity and misalignment in longitudinal data.
Time-series classification is a well-studied area of research. For an in-depth review of sequence classification, we refer the reader to @cite_15 . Briefly, most time-series classification approaches focus on either (a) defining a measure of dis similarity between raw signals or (b) on extracting features such as motifs shapelets statistical summaries from the data @cite_8 @cite_17 @cite_20 @cite_9 @cite_10 @cite_26 . We focus on the first setting, in which we consider the entirety of the signal. We believe this is particularly important in settings where there is a paucity of data available. Such settings are common important in the healthcare domain, where collecting patient data is often expensive and labor intensive. In addition, we limit our analysis to interpretable models. While others have proposed time-series classification techniques using a deep learning framework @cite_13 @cite_27 @cite_1 , such approaches do not apply to a setting like ours in which the number of training points is relatively small and the time series relatively short, and yield predictions that are hard to interpret limiting their utility.
@cite_13 @cite_26 @cite_8 @cite_9 @cite_1 @cite_27 @cite_15 @cite_10 @cite_20 @cite_17
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Electrocardiographic measures can facilitate the identification of patients at risk of death after acute coronary syndromes. This study evaluates a new risk metric, morphologic variability (MV), which measures beat-to-beat variability in the shape of the entire heart beat signal. This metric is analogous to heart rate variability (HRV) approaches, which focus on beat-to-beat changes in the heart rate. MV was calculated using a dynamic time-warping technique in 764 patients from the DISPERSE2 (TIMI 33) trial for whom 24-hour continuous electrocardiograph was recorded within 48 hours of non-ST-elevation acute coronary syndrome. The patients were evaluated during a 90-day follow-up for the end point of death. Patients with high MV showed an increased risk of death during follow-up (hazard ratio 8.46; p Several important time series data mining problems reduce to the core task of finding approximately repeated subsequences in a longer time series. In an earlier work, we formalized the idea of approximately repeated subsequences by introducing the notion of time series motifs. Two limitations of this work were the poor scalability of the motif discovery algorithm, and the inability to discover motifs in the presence of noise.Here we address these limitations by introducing a novel algorithm inspired by recent advances in the problem of pattern discovery in biosequences. Our algorithm is probabilistic in nature, but as we show empirically and theoretically, it can find time series motifs with very high probability even in the presence of noise or "don't care" symbols. Not only is the algorithm fast, but it is an anytime algorithm, producing likely candidate motifs almost immediately, and gradually improving the quality of results over time. We demonstrate a simple strategy to cope with missing data in sequential inputs, addressing the task of multilabel classification of diagnoses given clinical time series. Collected from the pediatric intensive care unit (PICU) at Children's Hospital Los Angeles, our data consists of multivariate time series of observations. The measurements are irregularly spaced, leading to missingness patterns in temporally discretized sequences. While these artifacts are typically handled by imputation, we achieve superior predictive performance by treating the artifacts as features. Unlike linear models, recurrent neural networks can realize this improvement using only simple binary indicators of missingness. For linear models, we show an alternative strategy to capture this signal. Training models on missingness patterns only, we show that for some diseases, what tests are run can be as predictive as the results themselves. We present and evaluate the capacity of a deep neural network to learn robust features from EEG to automatically detect seizures. This is a challenging problem because seizure manifestations on EEG are extremely variable both inter- and intra-patient. By simultaneously capturing spectral, temporal and spatial information our recurrent convolutional neural network learns a general spatially invariant representation of a seizure. The proposed approach exceeds significantly previous results obtained on cross-patient classifiers both in terms of sensitivity and false positive rate. Furthermore, our model proves to be robust to missing channel and variable electrode montage. ICU mortality risk prediction may help clinicians take effective interventions to improve patient outcome. Existing machine learning approaches often face challenges in integrating a comprehensive panel of physiologic variables and presenting to clinicians interpretable models. We aim to improve both accuracy and interpretability of prediction models by introducing Subgraph Augmented Non-negative Matrix Factorization (SANMF) on ICU physiologic time series. SANMF converts time series into a graph representation and applies frequent subgraph mining to automatically extract temporal trends. We then apply non-negative matrix factorization to group trends in a way that approximates patient pathophysiologic states. Trend groups are then used as features in training a logistic regression model for mortality risk prediction, and are also ranked according to their contribution to mortality risk. We evaluated SANMF against four empirical models on the task of predicting mortality or survival 30 days after discharge from ICU using the observed physiologic measurements between 12 and 24 hours after admission. SANMF outperforms all comparison models, and in particular, demonstrates an improvement in AUC (0.848 vs. 0.827, p<0.002) compared to a state-of-the-art machine learning method that uses manual feature engineering. Feature analysis was performed to illuminate insights and benefits of subgraph groups in mortality risk prediction. The last decade has witnessed a tremendous growths of interests in applications that deal with querying and mining of time series data. Numerous representation methods for dimensionality reduction and similarity measures geared towards time series have been introduced. Each individual work introducing a particular method has made specific claims and, aside from the occasional theoretical justifications, provided quantitative experimental observations. However, for the most part, the comparative aspects of these experiments were too narrowly focused on demonstrating the benefits of the proposed methods over some of the previously introduced ones. In order to provide a comprehensive validation, we conducted an extensive set of time series experiments re-implementing 8 different representation methods and 9 similarity measures and their variants, and testing their effectiveness on 38 time series data sets from a wide variety of application domains. In this paper, we give an overview of these different techniques and present our comparative experimental findings regarding their effectiveness. Our experiments have provided both a unified validation of some of the existing achievements, and in some cases, suggested that certain claims in the literature may be unduly optimistic.