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A Review of Deep Learning Methods for Irregularly Sampled Medical Time Series Data

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 Added by Chenxi Sun
 Publication date 2020
and research's language is English




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Irregularly sampled time series (ISTS) data has irregular temporal intervals between observations and different sampling rates between sequences. ISTS commonly appears in healthcare, economics, and geoscience. Especially in the medical environment, the widely used Electronic Health Records (EHRs) have abundant typical irregularly sampled medical time series (ISMTS) data. Developing deep learning methods on EHRs data is critical for personalized treatment, precise diagnosis and medical management. However, it is challenging to directly use deep learning models for ISMTS data. On the one hand, ISMTS data has the intra-series and inter-series relations. Both the local and global structures should be considered. On the other hand, methods should consider the trade-off between task accuracy and model complexity and remain generality and interpretability. So far, many existing works have tried to solve the above problems and have achieved good results. In this paper, we review these deep learning methods from the perspectives of technology and task. Under the technology-driven perspective, we summarize them into two categories - missing data-based methods and raw data-based methods. Under the task-driven perspective, we also summarize them into two categories - data imputation-oriented and downstream task-oriented. For each of them, we point out their advantages and disadvantages. Moreover, we implement some representative methods and compare them on four medical datasets with two tasks. Finally, we discuss the challenges and opportunities in this area.



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Recurrent neural networks (RNNs) with continuous-time hidden states are a natural fit for modeling irregularly-sampled time series. These models, however, face difficulties when the input data possess long-term dependencies. We prove that similar to standard RNNs, the underlying reason for this issue is the vanishing or exploding of the gradient during training. This phenomenon is expressed by the ordinary differential equation (ODE) representation of the hidden state, regardless of the ODE solvers choice. We provide a solution by designing a new algorithm based on the long short-term memory (LSTM) that separates its memory from its time-continuous state. This way, we encode a continuous-time dynamical flow within the RNN, allowing it to respond to inputs arriving at arbitrary time-lags while ensuring a constant error propagation through the memory path. We call these RNN models ODE-LSTMs. We experimentally show that ODE-LSTMs outperform advanced RNN-based counterparts on non-uniformly sampled data with long-term dependencies. All code and data is available at https://github.com/mlech26l/ode-lstms.
Electronic health record (EHR) data is sparse and irregular as it is recorded at irregular time intervals, and different clinical variables are measured at each observation point. In this work, we propose a multi-view features integration learning from irregular multivariate time series data by self-attention mechanism in an imputation-free manner. Specifically, we devise a novel multi-integration attention module (MIAM) to extract complex information inherent in irregular time series data. In particular, we explicitly learn the relationships among the observed values, missing indicators, and time interval between the consecutive observations, simultaneously. The rationale behind our approach is the use of human knowledge such as what to measure and when to measure in different situations, which are indirectly represented in the data. In addition, we build an attention-based decoder as a missing value imputer that helps empower the representation learning of the inter-relations among multi-view observations for the prediction task, which operates at the training phase only. We validated the effectiveness of our method over the public MIMIC-III and PhysioNet challenge 2012 datasets by comparing with and outperforming the state-of-the-art methods for in-hospital mortality prediction.
249 - Yang Jiao , Kai Yang , Shaoyu Dou 2020
Multivariate time series (MTS) data are becoming increasingly ubiquitous in diverse domains, e.g., IoT systems, health informatics, and 5G networks. To obtain an effective representation of MTS data, it is not only essential to consider unpredictable dynamics and highly variable lengths of these data but also important to address the irregularities in the sampling rates of MTS. Existing parametric approaches rely on manual hyperparameter tuning and may cost a huge amount of labor effort. Therefore, it is desirable to learn the representation automatically and efficiently. To this end, we propose an autonomous representation learning approach for multivariate time series (TimeAutoML) with irregular sampling rates and variable lengths. As opposed to previous works, we first present a representation learning pipeline in which the configuration and hyperparameter optimization are fully automatic and can be tailored for various tasks, e.g., anomaly detection, clustering, etc. Next, a negative sample generation approach and an auxiliary classification task are developed and integrated within TimeAutoML to enhance its representation capability. Extensive empirical studies on real-world datasets demonstrate that the proposed TimeAutoML outperforms competing approaches on various tasks by a large margin. In fact, it achieves the best anomaly detection performance among all comparison algorithms on 78 out of all 85 UCR datasets, acquiring up to 20% performance improvement in terms of AUC score.
Continuous, automated surveillance systems that incorporate machine learning models are becoming increasingly more common in healthcare environments. These models can capture temporally dependent changes across multiple patient variables and can enhance a clinicians situational awareness by providing an early warning alarm of an impending adverse event such as sepsis. However, most commonly used methods, e.g., XGBoost, fail to provide an interpretable mechanism for understanding why a model produced a sepsis alarm at a given time. The black-box nature of many models is a severe limitation as it prevents clinicians from independently corroborating those physiologic features that have contributed to the sepsis alarm. To overcome this limitation, we propose a generalized linear model (GLM) approach to fit a Granger causal graph based on the physiology of several major sepsis-associated derangements (SADs). We adopt a recently developed stochastic monotone variational inequality-based estimator coupled with forwarding feature selection to learn the graph structure from both continuous and discrete-valued as well as regularly and irregularly sampled time series. Most importantly, we develop a non-asymptotic upper bound on the estimation error for any monotone link function in the GLM. We conduct real-data experiments and demonstrate that our proposed method can achieve comparable performance to popular and powerful prediction methods such as XGBoost while simultaneously maintaining a high level of interpretability.
Prediction based on Irregularly Sampled Time Series (ISTS) is of wide concern in the real-world applications. For more accurate prediction, the methods had better grasp more data characteristics. Different from ordinary time series, ISTS is characterised with irregular time intervals of intra-series and different sampling rates of inter-series. However, existing methods have suboptimal predictions due to artificially introducing new dependencies in a time series and biasedly learning relations among time series when modeling these two characteristics. In this work, we propose a novel Time Encoding (TE) mechanism. TE can embed the time information as time vectors in the complex domain. It has the the properties of absolute distance and relative distance under different sampling rates, which helps to represent both two irregularities of ISTS. Meanwhile, we create a new model structure named Time Encoding Echo State Network (TE-ESN). It is the first ESNs-based model that can process ISTS data. Besides, TE-ESN can incorporate long short-term memories and series fusion to grasp horizontal and vertical relations. Experiments on one chaos system and three real-world datasets show that TE-ESN performs better than all baselines and has better reservoir property.

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