RAM-EHR: Retrieval Augmentation Meets Clinical Predictions on Electronic Health Records

We present RAM-EHR, a Retrieval AugMentation pipeline to improve clinical predictions on Electronic Health Records (EHRs). RAM-EHR first collects multiple knowledge sources, converts them into text format, and uses dense retrieval to obtain information related to medical concepts. This strategy addresses the difficulties associated with complex names for the concepts. RAM-EHR then augments the local EHR predictive model co-trained with consistency regularization to capture complementary information from patient visits and summarized knowledge. Experiments on two EHR datasets show the efficacy of RAM-EHR over previous knowledge-enhanced baselines (3.4% gain in AUROC and 7.2% gain in AUPR), emphasizing the effectiveness of the summarized knowledge from RAM-EHR for clinical prediction tasks. The code will be published at \url{https://github.com/ritaranx/RAM-EHR}.

EHRAgent: Code Empowers Large Language Models for Complex Tabular Reasoning on Electronic Health Records

Large language models (LLMs) have demonstrated exceptional capabilities in planning and tool utilization as autonomous agents, but few have been developed for medical problem-solving. We propose EHRAgent1, an LLM agent empowered with a code interface, to autonomously generate and execute code for complex clinical tasks within electronic health records (EHRs). First, we formulate an EHR question-answering task into a tool-use planning process, efficiently decomposing a complicated task into a sequence of manageable actions. By integrating interactive coding and execution feedback, EHRAgent learns from error messages and improves the originally generated code through iterations. Furthermore, we enhance the LLM agent by incorporating long-term memory, which allows EHRAgent to effectively select and build upon the most relevant successful cases from past experiences. Experiments on two real-world EHR datasets show that EHRAgent outperforms the strongest LLM agent baseline by 36.48% and 12.41%, respectively. EHRAgent leverages the emerging few-shot learning capabilities of LLMs, enabling autonomous code generation and execution to tackle complex clinical tasks with minimal demonstrations.

Explainable Artificial Intelligence Methods in Combating Pandemics: A Systematic Review

Despite the myriad peer-reviewed papers demonstrating novel Artificial Intelligence (AI)-based solutions to COVID-19 challenges during the pandemic, few have made significant clinical impact. The impact of artificial intelligence during the COVID-19 pandemic was greatly limited by lack of model transparency. This systematic review examines the use of Explainable Artificial Intelligence (XAI) during the pandemic and how its use could overcome barriers to real-world success. We find that successful use of XAI can improve model performance, instill trust in the end-user, and provide the value needed to affect user decision-making. We introduce the reader to common XAI techniques, their utility, and specific examples of their application. Evaluation of XAI results is also discussed as an important step to maximize the value of AI-based clinical decision support systems. We illustrate the classical, modern, and potential future trends of XAI to elucidate the evolution of novel XAI techniques. Finally, we provide a checklist of suggestions during the experimental design process supported by recent publications. Common challenges during the implementation of AI solutions are also addressed with specific examples of potential solutions. We hope this review may serve as a guide to improve the clinical impact of future AI-based solutions.

Public Health Informatics: Proposing Causal Sequence of Death Using Neural Machine Translation

Each year there are nearly 57 million deaths around the world, with over 2.7 million in the United States. Timely, accurate and complete death reporting is critical in public health, as institutions and government agencies rely on death reports to analyze vital statistics and to formulate responses to communicable diseases. Inaccurate death reporting may result in potential misdirection of public health policies. Determining the causes of death is, nevertheless, challenging even for experienced physicians. To facilitate physicians in accurately reporting causes of death, we present an advanced AI approach to determine a chronically ordered sequence of clinical conditions that lead to death, based on decedent's last hospital admission discharge record. The sequence of clinical codes on the death report is named as causal chain of death, coded in the tenth revision of International Statistical Classification of Diseases (ICD-10); the priority-ordered clinical conditions on the discharge record are coded in ICD-9. We identify three challenges in proposing the causal chain of death: two versions of coding system in clinical codes, medical domain knowledge conflict, and data interoperability. To overcome the first challenge in this sequence-to-sequence problem, we apply neural machine translation models to generate target sequence. We evaluate the quality of generated sequences with the BLEU (BiLingual Evaluation Understudy) score and achieve 16.44 out of 100. To address the second challenge, we incorporate expert-verified medical domain knowledge as constraint in generating output sequence to exclude infeasible causal chains. Lastly, we demonstrate the usability of our work in a Fast Healthcare Interoperability Resources (FHIR) interface to address the third challenge.

DeepDeath: Learning to Predict the Underlying Cause of Death with Big Data

Multiple cause-of-death data provides a valuable source of information that can be used to enhance health standards by predicting health related trajectories in societies with large populations. These data are often available in large quantities across U.S. states and require Big Data techniques to uncover complex hidden patterns. We design two different classes of models suitable for large-scale analysis of mortality data, a Hadoop-based ensemble of random forests trained over N-grams, and the DeepDeath, a deep classifier based on the recurrent neural network (RNN). We apply both classes to the mortality data provided by the National Center for Health Statistics and show that while both perform significantly better than the random classifier, the deep model that utilizes long short-term memory networks (LSTMs), surpasses the N-gram based models and is capable of learning the temporal aspect of the data without a need for building ad-hoc, expert-driven features.

MotifMark: Finding Regulatory Motifs in DNA Sequences

The interaction between proteins and DNA is a key driving force in a significant number of biological processes such as transcriptional regulation, repair, recombination, splicing, and DNA modification. The identification of DNA-binding sites and the specificity of target proteins in binding to these regions are two important steps in understanding the mechanisms of these biological activities. A number of high-throughput technologies have recently emerged that try to quantify the affinity between proteins and DNA motifs. Despite their success, these technologies have their own limitations and fall short in precise characterization of motifs, and as a result, require further downstream analysis to extract useful and interpretable information from a haystack of noisy and inaccurate data. Here we propose MotifMark, a new algorithm based on graph theory and machine learning, that can find binding sites on candidate probes and rank their specificity in regard to the underlying transcription factor. We developed a pipeline to analyze experimental data derived from compact universal protein binding microarrays and benchmarked it against two of the most accurate motif search methods. Our results indicate that MotifMark can be a viable alternative technique for prediction of motif from protein binding microarrays and possibly other related high-throughput techniques.

DeeperBind: Enhancing Prediction of Sequence Specificities of DNA Binding Proteins

Transcription factors (TFs) are macromolecules that bind to \textit{cis}-regulatory specific sub-regions of DNA promoters and initiate transcription. Finding the exact location of these binding sites (aka motifs) is important in a variety of domains such as drug design and development. To address this need, several \textit{in vivo} and \textit{in vitro} techniques have been developed so far that try to characterize and predict the binding specificity of a protein to different DNA loci. The major problem with these techniques is that they are not accurate enough in prediction of the binding affinity and characterization of the corresponding motifs. As a result, downstream analysis is required to uncover the locations where proteins of interest bind. Here, we propose DeeperBind, a long short term recurrent convolutional network for prediction of protein binding specificities with respect to DNA probes. DeeperBind can model the positional dynamics of probe sequences and hence reckons with the contributions made by individual sub-regions in DNA sequences, in an effective way. Moreover, it can be trained and tested on datasets containing varying-length sequences. We apply our pipeline to the datasets derived from protein binding microarrays (PBMs), an in-vitro high-throughput technology for quantification of protein-DNA binding preferences, and present promising results. To the best of our knowledge, this is the most accurate pipeline that can predict binding specificities of DNA sequences from the data produced by high-throughput technologies through utilization of the power of deep learning for feature generation and positional dynamics modeling.

A Multi-Modal Graph-Based Semi-Supervised Pipeline for Predicting Cancer Survival

Cancer survival prediction is an active area of research that can help prevent unnecessary therapies and improve patient's quality of life. Gene expression profiling is being widely used in cancer studies to discover informative biomarkers that aid predict different clinical endpoint prediction. We use multiple modalities of data derived from RNA deep-sequencing (RNA-seq) to predict survival of cancer patients. Despite the wealth of information available in expression profiles of cancer tumors, fulfilling the aforementioned objective remains a big challenge, for the most part, due to the paucity of data samples compared to the high dimension of the expression profiles. As such, analysis of transcriptomic data modalities calls for state-of-the-art big-data analytics techniques that can maximally use all the available data to discover the relevant information hidden within a significant amount of noise. In this paper, we propose a pipeline that predicts cancer patients' survival by exploiting the structure of the input (manifold learning) and by leveraging the unlabeled samples using Laplacian support vector machines, a graph-based semi supervised learning (GSSL) paradigm. We show that under certain circumstances, no single modality per se will result in the best accuracy and by fusing different models together via a stacked generalization strategy, we may boost the accuracy synergistically. We apply our approach to two cancer datasets and present promising results. We maintain that a similar pipeline can be used for predictive tasks where labeled samples are expensive to acquire.

A Semi-Supervised Method for Predicting Cancer Survival Using Incomplete Clinical Data

Prediction of survival for cancer patients is an open area of research. However, many of these studies focus on datasets with a large number of patients. We present a novel method that is specifically designed to address the challenge of data scarcity, which is often the case for cancer datasets. Our method is able to use unlabeled data to improve classification by adopting a semi-supervised training approach to learn an ensemble classifier. The results of applying our method to three cancer datasets show the promise of semi-supervised learning for prediction of cancer survival.