Time-Series Embedded Feature Selection Using Deep Learning: Data Mining Electronic Health Records for Novel Biomarkers

As health information technologies continue to advance, routine collection and digitisation of patient health records in the form of electronic health records present as an ideal opportunity for data-mining and exploratory analysis of biomarkers and risk factors indicative of a potentially diverse domain of patient outcomes. Patient records have continually become more widely available through various initiatives enabling open access whilst maintaining critical patient privacy. In spite of such progress, health records remain not widely adopted within the current clinical statistical analysis domain due to challenging issues derived from such “big data”.Deep learning based temporal modelling approaches present an ideal solution to health record challenges through automated self-optimisation of representation learning, able to man-ageably compose the high-dimensional domain of patient records into data representations able to model complex data associations. Such representations can serve to condense and reduce dimensionality to emphasise feature sparsity and importance through novel embedded feature selection approaches. Accordingly, application towards patient records enable complex mod-elling and analysis of the full domain of clinical features to select biomarkers of predictive relevance.Firstly, we propose a novel entropy regularised neural network ensemble able to highlight risk factors associated with hospitalisation risk of individuals with dementia. The application of which, was able to reduce a large domain of unique medical events to a small set of relevant risk factors able to maintain hospitalisation discrimination.Following on, we continue our work on ensemble architecture approaches with a novel cas-cading LSTM ensembles to predict severe sepsis onset within critical patients in an ICU critical care centre. We demonstrate state-of-the-art performance capabilities able to outperform that of current related literature.Finally, we propose a novel embedded feature selection application dubbed 1D convolu-tion feature selection using sparsity regularisation. Said methodology was evaluated on both domains of dementia and sepsis prediction objectives to highlight model capability and generalisability. We further report a selection of potential biomarkers for the aforementioned case study objectives highlighting clinical relevance and potential novelty value for future clinical analysis.Accordingly, we demonstrate the effective capability of embedded feature selection ap-proaches through the application of temporal based deep learning architectures in the discovery of effective biomarkers across a variety of challenging clinical applications

Rescue therapy for vasospasm following aneurysmal subarachnoid hemorrhage:a propensity score-matched analysis with machine learning

OBJECTIVE Rescue therapies have been recommended for patients with angiographic vasospasm (aVSP) and delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH). However, there is little evidence from randomized clinical trials that these therapies are safe and effective. The primary aim of this study was to apply game theory-based methods in explainable machine learning (ML) and propensity score matching to determine if rescue therapy was associated with better 3-month outcomes following post-SAH aVSP and DCI. The authors also sought to use these explainable ML methods to identify patient populations that were more likely to receive rescue therapy and factors associated with better outcomes after rescue therapy. METHODS Data for patients with aVSP or DCI after SAH were obtained from 8 clinical trials and 1 observational study in the Subarachnoid Hemorrhage International Trialists repository. Gradient boosting ML models were constructed for each patient to predict the probability of receiving rescue therapy and the 3-month Glasgow Outcome Scale (GOS) score. Favorable outcome was defined as a 3-month GOS score of 4 or 5. Shapley Additive Explanation (SNAP) values were calculated for each patient-derived model to quantify feature importance and interaction effects. Variables with high S HAP importance in predicting rescue therapy administration were used in a propensity score-matched analysis of rescue therapy and 3-month GOS scores. RESULTS The authors identified 1532 patients with aVSP or DCI. Predictive, explainable ML models revealed that aneurysm characteristics and neurological complications, but not admission neurological scores, carried the highest relative importance rankings in predicting whether rescue therapy was administered. Younger age and absence of cerebral ischemia/ infarction were invariably linked to better rescue outcomes, whereas the other important predictors of outcome varied by rescue type (interventional or noninterventional). In a propensity score-matched analysis guided by SHAP-based variable selection, rescue therapy was associated with higher odds of 3-month GOS scores of 4-5 (OR 1.63, 95% CI 1.22-2.17). CONCLUSIONS Rescue therapy may increase the odds of good outcome in patients with aVSP or DCI after SAH. Given the strong association between cerebral ischemia/infarction and poor outcome, trials focusing on preventative or therapeutic interventions in these patients may be most able to demonstrate improvements in clinical outcomes. Insights developed from these models may be helpful for improving patient selection and trial design

Analyzing Granger causality in climate data with time series classification methods

Attribution studies in climate science aim for scientifically ascertaining the influence of climatic variations on natural or anthropogenic factors. Many of those studies adopt the concept of Granger causality to infer statistical cause-effect relationships, while utilizing traditional autoregressive models. In this article, we investigate the potential of state-of-the-art time series classification techniques to enhance causal inference in climate science. We conduct a comparative experimental study of different types of algorithms on a large test suite that comprises a unique collection of datasets from the area of climate-vegetation dynamics. The results indicate that specialized time series classification methods are able to improve existing inference procedures. Substantial differences are observed among the methods that were tested

Machine Learning Models for High-dimensional Biomedical Data

abstract: The recent technological advances enable the collection of various complex, heterogeneous and high-dimensional data in biomedical domains. The increasing availability of the high-dimensional biomedical data creates the needs of new machine learning models for effective data analysis and knowledge discovery. This dissertation introduces several unsupervised and supervised methods to help understand the data, discover the patterns and improve the decision making. All the proposed methods can generalize to other industrial fields. The first topic of this dissertation focuses on the data clustering. Data clustering is often the first step for analyzing a dataset without the label information. Clustering high-dimensional data with mixed categorical and numeric attributes remains a challenging, yet important task. A clustering algorithm based on tree ensembles, CRAFTER, is proposed to tackle this task in a scalable manner. The second part of this dissertation aims to develop data representation methods for genome sequencing data, a special type of high-dimensional data in the biomedical domain. The proposed data representation method, Bag-of-Segments, can summarize the key characteristics of the genome sequence into a small number of features with good interpretability. The third part of this dissertation introduces an end-to-end deep neural network model, GCRNN, for time series classification with emphasis on both the accuracy and the interpretation. GCRNN contains a convolutional network component to extract high-level features, and a recurrent network component to enhance the modeling of the temporal characteristics. A feed-forward fully connected network with the sparse group lasso regularization is used to generate the final classification and provide good interpretability. The last topic centers around the dimensionality reduction methods for time series data. A good dimensionality reduction method is important for the storage, decision making and pattern visualization for time series data. The CRNN autoencoder is proposed to not only achieve low reconstruction error, but also generate discriminative features. A variational version of this autoencoder has great potential for applications such as anomaly detection and process control.Dissertation/ThesisDoctoral Dissertation Industrial Engineering 201

Artificial intelligence for clinical decision support for monitoring patients in cardiovascular ICUs: a systematic review

Background: Artificial intelligence (AI) and machine learning (ML) models continue to evolve the clinical decision support systems (CDSS). However, challenges arise when it comes to the integration of AI/ML into clinical scenarios. In this systematic review, we followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA), the population, intervention, comparator, outcome, and study design (PICOS), and the medical AI life cycle guidelines to investigate studies and tools which address AI/ML-based approaches towards clinical decision support (CDS) for monitoring cardiovascular patients in intensive care units (ICUs). We further discuss recent advances, pitfalls, and future perspectives towards effective integration of AI into routine practices as were identified and elaborated over an extensive selection process for state-of-the-art manuscripts. Methods: Studies with available English full text from PubMed and Google Scholar in the period from January 2018 to August 2022 were considered. The manuscripts were fetched through a combination of the search keywords including AI, ML, reinforcement learning (RL), deep learning, clinical decision support, and cardiovascular critical care and patients monitoring. The manuscripts were analyzed and filtered based on qualitative and quantitative criteria such as target population, proper study design, cross-validation, and risk of bias. Results: More than 100 queries over two medical search engines and subjective literature research were developed which identified 89 studies. After extensive assessments of the studies both technically and medically, 21 studies were selected for the final qualitative assessment. Discussion: Clinical time series and electronic health records (EHR) data were the most common input modalities, while methods such as gradient boosting, recurrent neural networks (RNNs) and RL were mostly used for the analysis. Seventy-five percent of the selected papers lacked validation against external datasets highlighting the generalizability issue. Also, interpretability of the AI decisions was identified as a central issue towards effective integration of AI in healthcare

Interval Temporal Random Forests with an Application to COVID-19 Diagnosis

Symbolic learning is the logic-based approach to machine learning. The mission of symbolic learning is to provide algorithms and methodologies to extract logical information from data and express it in an interpretable way. In the context of temporal data, interval temporal logic has been recently proposed as a suitable tool for symbolic learning, specifically via the design of an interval temporal logic decision tree extraction algorithm. Building on it, we study here its natural generalization to interval temporal random forests, mimicking the corresponding schema at the propositional level. Interval temporal random forests turn out to be a very performing multivariate time series classification method, which, despite the introduction of a functional component, are still logically interpretable to some extent. We apply this method to the problem of diagnosing COVID-19 based on the time series that emerge from cough and breath recording of positive versus negative subjects. Our experiment show that our models achieve very high accuracies and sensitivities, often superior to those achieved by classical methods on the same data. Although other recent approaches to the same problem (based on different and more numerous data) show even better statistical results, our solution is the first logic-based, interpretable, and explainable one

Methods for generating and evaluating synthetic longitudinal patient data: a systematic review

The proliferation of data in recent years has led to the advancement and utilization of various statistical and deep learning techniques, thus expediting research and development activities. However, not all industries have benefited equally from the surge in data availability, partly due to legal restrictions on data usage and privacy regulations, such as in medicine. To address this issue, various statistical disclosure and privacy-preserving methods have been proposed, including the use of synthetic data generation. Synthetic data are generated based on some existing data, with the aim of replicating them as closely as possible and acting as a proxy for real sensitive data. This paper presents a systematic review of methods for generating and evaluating synthetic longitudinal patient data, a prevalent data type in medicine. The review adheres to the PRISMA guidelines and covers literature from five databases until the end of 2022. The paper describes 17 methods, ranging from traditional simulation techniques to modern deep learning methods. The collected information includes, but is not limited to, method type, source code availability, and approaches used to assess resemblance, utility, and privacy. Furthermore, the paper discusses practical guidelines and key considerations for developing synthetic longitudinal data generation methods

Learning from Multi-Class Imbalanced Big Data with Apache Spark

With data becoming a new form of currency, its analysis has become a top priority in both academia and industry, furthering advancements in high-performance computing and machine learning. However, these large, real-world datasets come with additional complications such as noise and class overlap. Problems are magnified when with multi-class data is presented, especially since many of the popular algorithms were originally designed for binary data. Another challenge arises when the number of examples are not evenly distributed across all classes in a dataset. This often causes classifiers to favor the majority class over the minority classes, leading to undesirable results as learning from the rare cases may be the primary goal. Many of the classic machine learning algorithms were not designed for multi-class, imbalanced data or parallelism, and so their effectiveness has been hindered. This dissertation addresses some of these challenges with in-depth experimentation using novel implementations of machine learning algorithms using Apache Spark, a distributed computing framework based on the MapReduce model designed to handle very large datasets. Experimentation showed that many of the traditional classifier algorithms do not translate well to a distributed computing environment, indicating the need for a new generation of algorithms targeting modern high-performance computing. A collection of popular oversampling methods, originally designed for small binary class datasets, have been implemented using Apache Spark for the first time to improve parallelism and add multi-class support. An extensive study on how instance level difficulty affects the learning from large datasets was also performed

Text Classification

There is an abundance of text data in this world but most of it is raw. We need to extract information from this data to make use of it. One way to extract this information from raw text is to apply informative labels drawn from a pre-defined fixed set i.e. Text Classification. In this thesis, we focus on the general problem of text classification, and work towards solving challenges associated to binary/multi-class/multi-label classification. More specifically, we deal with the problem of (i) Zero-shot labels during testing; (ii) Active learning for text screening; (iii) Multi-label classification under low supervision; (iv) Structured label space; (v) Classifying pairs of words in raw text i.e. Relation Extraction. For (i), we use a zero-shot classification model that utilizes independently learned semantic embeddings. Regarding (ii), we propose a novel active learning algorithm that reduces problem of bias in naive active learning algorithms. For (iii), we propose neural candidate-selector architecture that starts from a set of high-recall candidate labels to obtain high-precision predictions. In the case of (iv), we proposed an attention based neural tree decoder that recursively decodes an abstract into the ontology tree. For (v), we propose using second-order relations that are derived by explicitly connecting pairs of words via context token(s) for improved relation extraction. We use a wide variety of both traditional and deep machine learning tools. More specifically, we used traditional machine learning models like multi-valued linear regression and logistic regression for (i, ii), deep convolutional neural networks for (iii), recurrent neural networks for (iv) and transformer networks for (v)