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1. GP-VAE: Deep Probabilistic Time Series Imputation

   Fortuin, V. (August 2020, International Conference on Artificial Intelligence and Statistics)

   Multivariate time series with missing values are common in areas such as healthcare and finance, and have grown in number and complexity over the years. This raises the question whether deep learning methodologies can outperform classical data imputation methods in this domain. However, naïve applications of deep learning fall short in giving reliable confidence estimates and lack interpretability. We propose a new deep sequential latent variable model for dimensionality reduction and data imputation. Our modeling assumption is simple and interpretable: the high dimensional time series has a lower-dimensional representation which evolves smoothly in time according to a Gaussian process. The nonlinear dimensionality reduction in the presence of missing data is achieved using a VAE approach with a novel structured variational approximation. We demonstrate that our approach outperforms several classical and deep learning-based data imputation methods on high-dimensional data from the domains of computer vision and healthcare, while additionally improving the smoothness of the imputations and providing interpretable uncertainty estimates. 

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2. Sparse Convolutional Denoising Autoencoders for Genotype Imputation

   https://doi.org/10.3390/genes10090652  

   Chen, Junjie; Shi, Xinghua (September 2019, Genes)

   Genotype imputation, where missing genotypes can be computationally imputed, is an essential tool in genomic analysis ranging from genome wide associations to phenotype prediction. Traditional genotype imputation methods are typically based on haplotype-clustering algorithms, hidden Markov models (HMMs), and statistical inference. Deep learning-based methods have been recently reported to suitably address the missing data problems in various fields. To explore the performance of deep learning for genotype imputation, in this study, we propose a deep model called a sparse convolutional denoising autoencoder (SCDA) to impute missing genotypes. We constructed the SCDA model using a convolutional layer that can extract various correlation or linkage patterns in the genotype data and applying a sparse weight matrix resulted from the L1 regularization to handle high dimensional data. We comprehensively evaluated the performance of the SCDA model in different scenarios for genotype imputation on the yeast and human genotype data, respectively. Our results showed that SCDA has strong robustness and significantly outperforms popular reference-free imputation methods. This study thus points to another novel application of deep learning models for missing data imputation in genomic studies. 

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3. Unsupervised Imputation of Non-Ignorably Missing Data Using Importance-Weighted Autoencoders

   https://doi.org/10.1080/19466315.2024.2368787  

   Lim, David K; Rashid, Naim U; Oliva, Junier B; Ibrahim, Joseph G (July 2024, Statistics in Biopharmaceutical Research)

   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 used 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. 

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4. Temporal Concept Tracing: Making Deep Learning PredictionsInterpretable and Actionable for ICU Acute Kidney InjuryPrevention

   https://doi.org/10.1609/aaaiss.v7i1.36917  

   Badhon, S_M_Saiful Islam; Bozdag, Serdar; Adibuzzaman, Mohammad; Cleveland, Ana D; Ding, Junhua; Hossain, KSM Tozammel (November 2025, Proceedings of the AAAI Symposium Series)

   Deep learning models have demonstrated impressive accuracy in predicting acute kidney injury (AKI), a condition affecting up to 20% of ICU patients, yet their black-box nature prevents clinical adoption in high-stakes critical care settings. While existing interpretability methods like SHAP, LIME, and attention mechanisms can identify important features, they fail to capture the temporal dynamics essential for clinical decision-making, and are unable to communicate when specific risk factors become critical in a patient's trajectory. This limitation is particularly problematic in the ICU, where the timing of interventions can significantly impact patient outcomes. We present a novel interpretable framework that brings temporal awareness to deep learning predictions for AKI. Our approach introduces three key innovations: (1) a latent convolutional concept bottleneck that learns clinically meaningful patterns from ICU time-series without requiring manual concept annotation, leveraging Conv1D layers to capture localized temporal patterns like sudden physiological changes; (2) Temporal Concept Tracing (TCT), a gradient-based method that identifies not only which risk factors matter but precisely when they become critical addressing the fundamental question of temporal relevance missing from current XAI techniques; and (3) integration with MedAlpaca to generate structured, time-aware clinical explanations that translate model insights into actionable bedside guidance. We evaluate our framework on MIMIC-IV data, demonstrating that our approach performs better than existing explainability frameworks, Occlusion and LIME, in terms of the comprehensiveness score, sufficiency score, and processing time. The proposed method also better captures risk factors inflection points for patients timelines compared to conventional concept bottleneck methods, including dense layer and attention mechanism. This work represents the first comprehensive solution for interpretable temporal deep learning in critical care that addresses both the what and when of clinical risk factors. By making AKI predictions transparent and temporally contextualized, our framework bridges the gap between model accuracy and clinical utility, offering a path toward trustworthy AI deployment in time-sensitive healthcare settings. 

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5. Self-Supervised Transformer for Sparse and Irregularly Sampled Multivariate Clinical Time-Series

   https://doi.org/10.1145/3516367  

   Tipirneni, Sindhu; Reddy, Chandan_K (July 2022, ACM Transactions on Knowledge Discovery from Data)

   Multivariate time-series data are frequently observed in critical care settings and are typically characterized by sparsity (missing information) and irregular time intervals. Existing approaches for learning representations in this domain handle these challenges by either aggregation or imputation of values, which in-turn suppresses the fine-grained information and adds undesirable noise/overhead into the machine learning model. To tackle this problem, we propose aSelf-supervisedTransformer forTime-Series (STraTS) model, which overcomes these pitfalls by treating time-series as a set of observation triplets instead of using the standard dense matrix representation. It employs a novel Continuous Value Embedding technique to encode continuous time and variable values without the need for discretization. It is composed of a Transformer component with multi-head attention layers, which enable it to learn contextual triplet embeddings while avoiding the problems of recurrence and vanishing gradients that occur in recurrent architectures. In addition, to tackle the problem of limited availability of labeled data (which is typically observed in many healthcare applications), STraTS utilizes self-supervision by leveraging unlabeled data to learn better representations by using time-series forecasting as an auxiliary proxy task. Experiments on real-world multivariate clinical time-series benchmark datasets demonstrate that STraTS has better prediction performance than state-of-the-art methods for mortality prediction, especially when labeled data is limited. Finally, we also present an interpretable version of STraTS, which can identify important measurements in the time-series data. Our data preprocessing and model implementation codes are available athttps://github.com/sindhura97/STraTS. 

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