Sepsis is an important cause of mortality, especially in intensive care unit (ICU) patients. Developing novel methods to identify early mortality is critical for improving survival outcomes in sepsis patients. Using the MIMIC-III database, we integrated demographic data, physiological measurements and clinical notes. We built and applied several machine learning models to predict the risk of hospital mortality and 30-day mortality in sepsis patients. From the clinical notes, we generated clinically meaningful word representations and embeddings. Supervised learning classifiers and a deep learning architecture were used to construct prediction models. The configurations that utilized both structured and unstructured clinical features yielded competitive F-measure of 0.512. Our results showed that the approaches integrating both structured and unstructured clinical features can be effectively applied to assist clinicians in identifying the risk of mortality in sepsis patients upon admission to the ICU.
Delirium is a common acute onset brain dysfunction in the emergency setting and is associated with higher mortality. It is difficult to detect and monitor since its presentations and risk factors can be different depending on the underlying medical condition of patients. In our study, we aimed to identify subtypes within the delirium population and build subgroup-specific predictive models to detect delirium using Medical Information Mart for Intensive Care IV (MIMIC-IV) data. We showed that clusters exist within the delirium population. Differences in feature importance were also observed for subgroup-specific predictive models. Our work could recalibrate existing delirium prediction models for each delirium subgroup and improve the precision of delirium detection and monitoring for ICU or emergency department patients who had highly heterogeneous medical conditions.
Federated learning is a distributed machine learning paradigm where multiple data owners (clients) collaboratively train one machine learning model while keeping data on their own devices. The heterogeneity of client datasets is one of the most important challenges of federated learning algorithms. Studies have found performance reduction with standard federated algorithms, such as FedAvg, on non-IID data. Many existing works on handling non-IID data adopt the same aggregation framework as FedAvg and focus on improving model updates either on the server side or on clients. In this work, we tackle this challenge in a different view by introducing redistribution rounds that delay the aggregation. We perform experiments on multiple tasks and show that the proposed framework significantly improves the performance on non-IID data.
We develop a regularization method which finds flat minima during the training of deep neural networks and other machine learning models. These minima generalize better than sharp minima, allowing models to better generalize to real word test data, which may be distributed differently from the training data. Specifically, we propose a method of regularized optimization to reduce the spectral radius of the Hessian of the loss function. Additionally, we derive algorithms to efficiently perform this optimization on neural networks and prove convergence results for these algorithms. Furthermore, we demonstrate that our algorithm works effectively on multiple real world applications in multiple domains including healthcare. In order to show our models generalize well, we introduce different methods of testing generalizability.
Genetic pathways usually encode molecular mechanisms that can inform targeted interventions. It is often challenging for existing machine learning approaches to jointly model genetic pathways (higher-order features) and variants (atomic features), and present to clinicians interpretable models. In order to build more accurate and better interpretable machine learning models for genetic medicine, we introduce Pathway Augmented Nonnegative Tensor factorization for HighER-order feature learning (PANTHER). PANTHER selects informative genetic pathways that directly encode molecular mechanisms. We apply genetically motivated constrained tensor factorization to group pathways in a way that reflects molecular mechanism interactions. We then train a softmax classifier for disease types using the identified pathway groups. We evaluated PANTHER against multiple state-of-the-art constrained tensor/matrix factorization models, as well as group guided and Bayesian hierarchical models. PANTHER outperforms all state-of-the-art comparison models significantly (p<0.05). Our experiments on large scale Next Generation Sequencing (NGS) and whole-genome genotyping datasets also demonstrated wide applicability of PANTHER. We performed feature analysis in predicting disease types, which suggested insights and benefits of the identified pathway groups.
Graph Neural Network (GNN) aggregates the neighborhood of each node into the node embedding and shows its powerful capability for graph representation learning. However, most existing GNN variants aggregate the neighborhood information in a fixed non-injective fashion, which may map different graphs or nodes to the same embedding, reducing the model expressiveness. We present a theoretical framework to design a continuous injective set function for neighborhood aggregation in GNN. Using the framework, we propose expressive GNN that aggregates the neighborhood of each node with a continuous injective set function, so that a GNN layer maps similar nodes with similar neighborhoods to similar embeddings, different nodes to different embeddings and the equivalent nodes or isomorphic graphs to the same embeddings. Moreover, the proposed expressive GNN can naturally learn expressive representations for graphs with continuous node attributes. We validate the proposed expressive GNN (ExpGNN) for graph classification on multiple benchmark datasets including simple graphs and attributed graphs. The experimental results demonstrate that our model achieves state-of-the-art performances on most of the benchmarks.
Joint image-text embedding extracted from medical images and associated contextual reports is the bedrock for most biomedical vision-and-language (V+L) tasks, including medical visual question answering, clinical image-text retrieval, clinical report auto-generation. In this study, we adopt four pre-trained V+L models: LXMERT, VisualBERT, UNIER and PixelBERT to learn multimodal representation from MIMIC-CXR radiographs and associated reports. The extrinsic evaluation on OpenI dataset shows that in comparison to the pioneering CNN-RNN model, the joint embedding learned by pre-trained V+L models demonstrate performance improvement in the thoracic findings classification task. We conduct an ablation study to analyze the contribution of certain model components and validate the advantage of joint embedding over text-only embedding. We also visualize attention maps to illustrate the attention mechanism of V+L models.
In inference, open-set classification is to either classify a sample into a known class from training or reject it as an unknown class. Existing deep open-set classifiers train explicit closed-set classifiers, in some cases disjointly utilizing reconstruction, which we find dilutes the latent representation's ability to distinguish unknown classes. In contrast, we train our model to cooperatively learn reconstruction and perform class-based clustering in the latent space. With this, our Gaussian mixture variational autoencoder (GMVAE) achieves more accurate and robust open-set classification results, with an average F1 improvement of 29.5%, through extensive experiments aided by analytical results.
Distributed representations of medical concepts have been used to support downstream clinical tasks recently. Electronic Health Records (EHR) capture different aspects of patients' hospital encounters and serve as a rich source for augmenting clinical decision making by learning robust medical concept embeddings. However, the same medical concept can be recorded in different modalities (e.g., clinical notes, lab results)-with each capturing salient information unique to that modality-and a holistic representation calls for relevant feature ensemble from all information sources. We hypothesize that representations learned from heterogeneous data types would lead to performance enhancement on various clinical informatics and predictive modeling tasks. To this end, our proposed approach makes use of meta-embeddings, embeddings aggregated from learned embeddings. Firstly, modality-specific embeddings for each medical concept is learned with graph autoencoders. The ensemble of all the embeddings is then modeled as a meta-embedding learning problem to incorporate their correlating and complementary information through a joint reconstruction. Empirical results of our model on both quantitative and qualitative clinical evaluations have shown improvements over state-of-the-art embedding models, thus validating our hypothesis.
Our research focuses on studying and developing methods for reducing the dimensionality of large datasets, common in biomedical applications. A major problem when learning information about patients based on genetic sequencing data is that there are often more feature variables (genetic data) than observations (patients). This makes direct supervised learning difficult. One way of reducing the feature space is to use latent Dirichlet allocation in order to group genetic variants in an unsupervised manner. Latent Dirichlet allocation is a common model in natural language processing, which describes a document as a mixture of topics, each with a probability of generating certain words. This can be generalized as a Bayesian tensor decomposition to account for multiple feature variables. While we made some progress improving and modifying these methods, our significant contributions are with hierarchical topic modeling. We developed distinct methods of incorporating hierarchical topic modeling, based on nested Chinese restaurant processes and Pachinko Allocation Machine, into Bayesian tensor decompositions. We apply these models to predict whether or not patients have autism spectrum disorder based on genetic sequencing data. We examine a dataset from National Database for Autism Research consisting of paired siblings -- one with autism, and the other without -- and counts of their genetic variants. Additionally, we linked the genes with their Reactome biological pathways. We combine this information into a tensor of patients, counts of their genetic variants, and the membership of these genes in pathways. Once we decompose this tensor, we use logistic regression on the reduced features in order to predict if patients have autism. We also perform a similar analysis of a dataset of patients with one of four common types of cancer (breast, lung, prostate, and colorectal).