LATTE: Label-efficient Incident Phenotyping from Longitudinal Electronic Health Records

Electronic health record (EHR) data are increasingly used to support real-world evidence (RWE) studies. Yet its ability to generate reliable RWE is limited by the lack of readily available precise information on the timing of clinical events such as the onset time of heart failure. We propose a LAbel-efficienT incidenT phEnotyping (LATTE) algorithm to accurately annotate the timing of clinical events from longitudinal EHR data. By leveraging the pre-trained semantic embedding vectors from large-scale EHR data as prior knowledge, LATTE selects predictive EHR features in a concept re-weighting module by mining their relationship to the target event and compresses their information into longitudinal visit embeddings through a visit attention learning network. LATTE employs a recurrent neural network to capture the sequential dependency between the target event and visit embeddings before/after it. To improve label efficiency, LATTE constructs highly informative longitudinal silver-standard labels from large-scale unlabeled patients to perform unsupervised pre-training and semi-supervised joint training. Finally, LATTE enhances cross-site portability via contrastive representation learning. LATTE is evaluated on three analyses: the onset of type-2 diabetes, heart failure, and the onset and relapses of multiple sclerosis. We use various evaluation metrics present in the literature including the $ABC_{gain}$, the proportion of reduction in the area between the observed event indicator and the predicted cumulative incidences in reference to the prediction per incident prevalence. LATTE consistently achieves substantial improvement over benchmark methods such as SAMGEP and RETAIN in all settings.

Unsupervised Ensemble Learning via Ising Model Approximation with Application to Phenotyping Prediction

Unsupervised ensemble learning has long been an interesting yet challenging problem that comes to prominence in recent years with the increasing demand of crowdsourcing in various applications. In this paper, we propose a novel method-- unsupervised ensemble learning via Ising model approximation (unElisa) that combines a pruning step with a predicting step. We focus on the binary case and use an Ising model to characterize interactions between the ensemble and the underlying true classifier. The presence of an edge between an observed classifier and the true classifier indicates a direct dependence whereas the absence indicates the corresponding one provides no additional information and shall be eliminated. This observation leads to the pruning step where the key is to recover the neighborhood of the true classifier. We show that it can be recovered successfully with exponentially decaying error in the high-dimensional setting by performing nodewise $\ell_1$-regularized logistic regression. The pruned ensemble allows us to get a consistent estimate of the Bayes classifier for predicting. We also propose an augmented version of majority voting by reversing all labels given by a subgroup of the pruned ensemble. We demonstrate the efficacy of our method through extensive numerical experiments and through the application to EHR-based phenotyping prediction on Rheumatoid Arthritis (RA) using data from Partners Healthcare System.