Objective: Computational phenotyping is a central informatics activity with resulting cohorts supporting a wide variety of applications. However, it is time-intensive because of manual data review, limited automation, and difficulties in adapting algorithms across sources. Since LLMs have demonstrated promising capabilities for text classification, comprehension, and generation, we posit they will perform well at repetitive manual review tasks traditionally performed by human experts. To support next-generation computational phenotyping methods, we developed SHREC, a framework for comprehensive integration of LLMs into end-to-end phenotyping pipelines. Materials and Methods: We applied and tested the ability of three lightweight LLMs (Gemma2 27 billion, Mistral Small 24 billion, and Phi-4 14 billion) to classify concepts and phenotype patients using previously developed phenotypes for ARF respiratory support therapies. Results: All models performed well on concept classification, with the best model (Mistral) achieving an AUROC of 0.896 across all relevant concepts. For phenotyping, models demonstrated near-perfect specificity for all phenotypes, and the top-performing model (Mistral) reached an average AUROC of 0.853 for single-therapy phenotypes, despite lower performance on multi-therapy phenotypes. Discussion: There are several advantages of LLMs that support their application to computational phenotyping, such as their ability to adapt to new tasks with prompt engineering alone and their ability to incorporate raw EHR data. Future steps to advance next-generation phenotyping methods include determining optimal strategies for integrating biomedical data, exploring how LLMs reason, and advancing generative model methods. Conclusion: Current lightweight LLMs can feasibly assist researchers with resource-intensive phenotyping tasks such as manual data review.
Phenotyping is the process of distinguishing groups of patients to identify different types of disease progression. A recent trend employs low-rank matrix and tensor factorization methods for their capability of dealing with multi-modal, heterogeneous, and missing data. Symptom quantification is crucial for understanding patient experiences in inflammatory bowel disease, especially in conditions such as ulcerative colitis (UC). However, patient-reported symptoms are typically noisy, subjective, and significantly more sparse than other data types. For this reason, they are usually not included in phenotyping and other machine learning methods. This paper explores the application of computational phenotyping to leverage Patient-Reported Outcomes (PROs) using a novel supervised coupled matrix-tensor factorization (SCMTF) method, which integrates temporal PROs and temporal labs with static features to predict medication persistence in ulcerative colitis. This is the first tensor-based method that is both supervised and coupled, it is the first application to the UC domain, and the first application to PROs. We use a deep learning framework that makes the model flexible and easy to train. The proposed method allows us to handle the large amount of missing data in the PROs. The best model predicts changes in medication 8 and 20 months in the future with AUCs of 0.853 and 0.803 on the test set respectively. We derive interpretable phenotypes consisting of static features and temporal features (including their temporal patterns). We show that low-rank matrix and tensor based phenotyping can be successfully applied to the UC domain and to highly missing PRO data. We identify phenotypes useful to predict medication persistence - these phenotypes include several symptom variables, showing that PROs contain relevant infromation that is usually discarded.
Computational phenotyping is essential for biomedical research but often requires significant time and resources, especially since traditional methods typically involve extensive manual data review. While machine learning and natural language processing advancements have helped, further improvements are needed. Few studies have explored using Large Language Models (LLMs) for these tasks despite known advantages of LLMs for text-based tasks. To facilitate further research in this area, we developed an evaluation framework, Evaluation of PHEnotyping for Observational Health Data (PHEONA), that outlines context-specific considerations. We applied and demonstrated PHEONA on concept classification, a specific task within a broader phenotyping process for Acute Respiratory Failure (ARF) respiratory support therapies. From the sample concepts tested, we achieved high classification accuracy, suggesting the potential for LLM-based methods to improve computational phenotyping processes.
Computational phenotyping allows for unsupervised discovery of subgroups of patients as well as corresponding co-occurring medical conditions from electronic health records (EHR). Typically, EHR data contains demographic information, diagnoses and laboratory results. Discovering (novel) phenotypes has the potential to be of prognostic and therapeutic value. Providing medical practitioners with transparent and interpretable results is an important requirement and an essential part for advancing precision medicine. Low-rank data approximation methods such as matrix (e.g., non-negative matrix factorization) and tensor decompositions (e.g., CANDECOMP/PARAFAC) have demonstrated that they can provide such transparent and interpretable insights. Recent developments have adapted low-rank data approximation methods by incorporating different constraints and regularizations that facilitate interpretability further. In addition, they offer solutions for common challenges within EHR data such as high dimensionality, data sparsity and incompleteness. Especially extracting temporal phenotypes from longitudinal EHR has received much attention in recent years. In this paper, we provide a comprehensive review of low-rank approximation-based approaches for computational phenotyping. The existing literature is categorized into temporal vs. static phenotyping approaches based on matrix vs. tensor decompositions. Furthermore, we outline different approaches for the validation of phenotypes, i.e., the assessment of clinical significance.
Tensor factorization has been proved as an efficient unsupervised learning approach for health data analysis, especially for computational phenotyping, where the high-dimensional Electronic Health Records (EHRs) with patients' history of medical procedures, medications, diagnosis, lab tests, etc., are converted to meaningful and interpretable medical concepts. Federated tensor factorization distributes the tensor computation to multiple workers under the coordination of a central server, which enables jointly learning the phenotypes across multiple hospitals while preserving the privacy of the patient information. However, existing federated tensor factorization algorithms encounter the single-point-failure issue with the involvement of the central server, which is not only easily exposed to external attacks but also limits the number of clients sharing information with the server under restricted uplink bandwidth. In this paper, we propose CiderTF, a communication-efficient decentralized generalized tensor factorization, which reduces the uplink communication cost by leveraging a four-level communication reduction strategy designed for a generalized tensor factorization, which has the flexibility of modeling different tensor distribution with multiple kinds of loss functions. Experiments on two real-world EHR datasets demonstrate that CiderTF achieves comparable convergence with a communication reduction up to 99.99%.
Non-negative tensor factorization has been shown a practical solution to automatically discover phenotypes from the electronic health records (EHR) with minimal human supervision. Such methods generally require an input tensor describing the inter-modal interactions to be pre-established; however, the correspondence between different modalities (e.g., correspondence between medications and diagnoses) can often be missing in practice. Although heuristic methods can be applied to estimate them, they inevitably introduce errors, and leads to sub-optimal phenotype quality. This is particularly important for patients with complex health conditions (e.g., in critical care) as multiple diagnoses and medications are simultaneously present in the records. To alleviate this problem and discover phenotypes from EHR with unobserved inter-modal correspondence, we propose the collective hidden interaction tensor factorization (cHITF) to infer the correspondence between multiple modalities jointly with the phenotype discovery. We assume that the observed matrix for each modality is marginalization of the unobserved inter-modal correspondence, which are reconstructed by maximizing the likelihood of the observed matrices. Extensive experiments conducted on the real-world MIMIC-III dataset demonstrate that cHITF effectively infers clinically meaningful inter-modal correspondence, discovers phenotypes that are more clinically relevant and diverse, and achieves better predictive performance compared with a number of state-of-the-art computational phenotyping models.
Images captured in a hazy environment usually suffer from bad visibility and missing information. Over many years, learning-based and handcrafted prior-based dehazing algorithms have been rigorously developed. However, both algorithms exhibit some weaknesses in terms of haze removal performance. Therefore, in this work, we have proposed the patch-map-based hybrid learning DehazeNet, which integrates these two strategies by using a hybrid learning technique involving the patch map and a bi-attentive generative adversarial network. In this method, the reasons limiting the performance of the dark channel prior (DCP) have been analyzed. A new feature called the patch map has been defined for selecting the patch size adaptively. Using this map, the limitations of the DCP (e.g., color distortion and failure to recover images involving white scenes) can be addressed efficiently. In addition, to further enhance the performance of the method for haze removal, a patch-map-based DCP has been embedded into the network, and this module has been trained with the atmospheric light generator, patch map selection module, and refined module simultaneously. A combination of traditional and learning-based methods can efficiently improve the haze removal performance of the network. Experimental results show that the proposed method can achieve better reconstruction results compared to other state-of-the-art haze removal algorithms.
Tensor factorization has been demonstrated as an efficient approach for computational phenotyping, where massive electronic health records (EHRs) are converted to concise and meaningful clinical concepts. While distributing the tensor factorization tasks to local sites can avoid direct data sharing, it still requires the exchange of intermediary results which could reveal sensitive patient information. Therefore, the challenge is how to jointly decompose the tensor under rigorous and principled privacy constraints, while still support the model's interpretability. We propose DPFact, a privacy-preserving collaborative tensor factorization method for computational phenotyping using EHR. It embeds advanced privacy-preserving mechanisms with collaborative learning. Hospitals can keep their EHR database private but also collaboratively learn meaningful clinical concepts by sharing differentially private intermediary results. Moreover, DPFact solves the heterogeneous patient population using a structured sparsity term. In our framework, each hospital decomposes its local tensors, and sends the updated intermediary results with output perturbation every several iterations to a semi-trusted server which generates the phenotypes. The evaluation on both real-world and synthetic datasets demonstrated that under strict privacy constraints, our method is more accurate and communication-efficient than state-of-the-art baseline methods.
This paper presents a Lisp architecture for a portable NLP system, termed LAPNLP, for processing clinical notes. LAPNLP integrates multiple standard, customized and in-house developed NLP tools. Our system facilitates portability across different institutions and data systems by incorporating an enriched Common Data Model (CDM) to standardize necessary data elements. It utilizes UMLS to perform domain adaptation when integrating generic domain NLP tools. It also features stand-off annotations that are specified by positional reference to the original document. We built an interval tree based search engine to efficiently query and retrieve the stand-off annotations by specifying positional requirements. We also developed a utility to convert an inline annotation format to stand-off annotations to enable the reuse of clinical text datasets with inline annotations. We experimented with our system on several NLP facilitated tasks including computational phenotyping for lymphoma patients and semantic relation extraction for clinical notes. These experiments showcased the broader applicability and utility of LAPNLP.
It has been recently shown that sparse, nonnegative tensor factorization of multi-modal electronic health record data is a promising approach to high-throughput computational phenotyping. However, such approaches typically do not leverage available domain knowledge while extracting the phenotypes; hence, some of the suggested phenotypes may not map well to clinical concepts or may be very similar to other suggested phenotypes. To address these issues, we present a novel, automatic approach called PIVETed-Granite that mines existing biomedical literature (PubMed) to obtain cannot-link constraints that are then used as side-information during a tensor-factorization based computational phenotyping process. The resulting improvements are clearly observed in experiments using a large dataset from VUMC to identify phenotypes for hypertensive patients.
Exponential growth in Electronic Healthcare Records (EHR) has resulted in new opportunities and urgent needs for discovery of meaningful data-driven representations and patterns of diseases in Computational Phenotyping research. Deep Learning models have shown superior performance for robust prediction in computational phenotyping tasks, but suffer from the issue of model interpretability which is crucial for clinicians involved in decision-making. In this paper, we introduce a novel knowledge-distillation approach called Interpretable Mimic Learning, to learn interpretable phenotype features for making robust prediction while mimicking the performance of deep learning models. Our framework uses Gradient Boosting Trees to learn interpretable features from deep learning models such as Stacked Denoising Autoencoder and Long Short-Term Memory. Exhaustive experiments on a real-world clinical time-series dataset show that our method obtains similar or better performance than the deep learning models, and it provides interpretable phenotypes for clinical decision making.
With large volumes of health care data comes the research area of computational phenotyping, making use of techniques such as machine learning to describe illnesses and other clinical concepts from the data itself. The "traditional" approach of using supervised learning relies on a domain expert, and has two main limitations: requiring skilled humans to supply correct labels limits its scalability and accuracy, and relying on existing clinical descriptions limits the sorts of patterns that can be found. For instance, it may fail to acknowledge that a disease treated as a single condition may really have several subtypes with different phenotypes, as seems to be the case with asthma and heart disease. Some recent papers cite successes instead using unsupervised learning. This shows great potential for finding patterns in Electronic Health Records that would otherwise be hidden and that can lead to greater understanding of conditions and treatments. This work implements a method derived strongly from Lasko et al., but implements it in Apache Spark and Python and generalizes it to laboratory time-series data in MIMIC-III. It is released as an open-source tool for exploration, analysis, and visualization, available at https://github.com/Hodapp87/mimic3_phenotyping
Health care is one of the most exciting frontiers in data mining and machine learning. Successful adoption of electronic health records (EHRs) created an explosion in digital clinical data available for analysis, but progress in machine learning for healthcare research has been difficult to measure because of the absence of publicly available benchmark data sets. To address this problem, we propose four clinical prediction benchmarks using data derived from the publicly available Medical Information Mart for Intensive Care (MIMIC-III) database. These tasks cover a range of clinical problems including modeling risk of mortality, forecasting length of stay, detecting physiologic decline, and phenotype classification. We propose strong linear and neural baselines for all four tasks and evaluate the effect of deep supervision, multitask training and data-specific architectural modifications on the performance of neural models.
Tensor factorization models offer an effective approach to convert massive electronic health records into meaningful clinical concepts (phenotypes) for data analysis. These models need a large amount of diverse samples to avoid population bias. An open challenge is how to derive phenotypes jointly across multiple hospitals, in which direct patient-level data sharing is not possible (e.g., due to institutional policies). In this paper, we developed a novel solution to enable federated tensor factorization for computational phenotyping without sharing patient-level data. We developed secure data harmonization and federated computation procedures based on alternating direction method of multipliers (ADMM). Using this method, the multiple hospitals iteratively update tensors and transfer secure summarized information to a central server, and the server aggregates the information to generate phenotypes. We demonstrated with real medical datasets that our method resembles the centralized training model (based on combined datasets) in terms of accuracy and phenotypes discovery while respecting privacy.
This article reviews recent advances in applying natural language processing (NLP) to Electronic Health Records (EHRs) for computational phenotyping. NLP-based computational phenotyping has numerous applications including diagnosis categorization, novel phenotype discovery, clinical trial screening, pharmacogenomics, drug-drug interaction (DDI) and adverse drug event (ADE) detection, as well as genome-wide and phenome-wide association studies. Significant progress has been made in algorithm development and resource construction for computational phenotyping. Among the surveyed methods, well-designed keyword search and rule-based systems often achieve good performance. However, the construction of keyword and rule lists requires significant manual effort, which is difficult to scale. Supervised machine learning models have been favored because they are capable of acquiring both classification patterns and structures from data. Recently, deep learning and unsupervised learning have received growing attention, with the former favored for its performance and the latter for its ability to find novel phenotypes. Integrating heterogeneous data sources have become increasingly important and have shown promise in improving model performance. Often better performance is achieved by combining multiple modalities of information. Despite these many advances, challenges and opportunities remain for NLP-based computational phenotyping, including better model interpretability and generalizability, and proper characterization of feature relations in clinical narratives
Accurately identifying distant recurrences in breast cancer from the Electronic Health Records (EHR) is important for both clinical care and secondary analysis. Although multiple applications have been developed for computational phenotyping in breast cancer, distant recurrence identification still relies heavily on manual chart review. In this study, we aim to develop a model that identifies distant recurrences in breast cancer using clinical narratives and structured data from EHR. We apply MetaMap to extract features from clinical narratives and also retrieve structured clinical data from EHR. Using these features, we train a support vector machine model to identify distant recurrences in breast cancer patients. We train the model using 1,396 double-annotated subjects and validate the model using 599 double-annotated subjects. In addition, we validate the model on a set of 4,904 single-annotated subjects as a generalization test. We obtained a high area under curve (AUC) score of 0.92 (SD=0.01) in the cross-validation using the training dataset, then obtained AUC scores of 0.95 and 0.93 in the held-out test and generalization test using 599 and 4,904 samples respectively. Our model can accurately and efficiently identify distant recurrences in breast cancer by combining features extracted from unstructured clinical narratives and structured clinical data.