Augmented Risk Prediction for the Onset of Alzheimer's Disease from Electronic Health Records with Large Language Models

Alzheimer's disease (AD) is the fifth-leading cause of death among Americans aged 65 and older. Screening and early detection of AD and related dementias (ADRD) are critical for timely intervention and for identifying clinical trial participants. The widespread adoption of electronic health records (EHRs) offers an important resource for developing ADRD screening tools such as machine learning based predictive models. Recent advancements in large language models (LLMs) demonstrate their unprecedented capability of encoding knowledge and performing reasoning, which offers them strong potential for enhancing risk prediction. This paper proposes a novel pipeline that augments risk prediction by leveraging the few-shot inference power of LLMs to make predictions on cases where traditional supervised learning methods (SLs) may not excel. Specifically, we develop a collaborative pipeline that combines SLs and LLMs via a confidence-driven decision-making mechanism, leveraging the strengths of SLs in clear-cut cases and LLMs in more complex scenarios. We evaluate this pipeline using a real-world EHR data warehouse from Oregon Health \& Science University (OHSU) Hospital, encompassing EHRs from over 2.5 million patients and more than 20 million patient encounters. Our results show that our proposed approach effectively combines the power of SLs and LLMs, offering significant improvements in predictive performance. This advancement holds promise for revolutionizing ADRD screening and early detection practices, with potential implications for better strategies of patient management and thus improving healthcare.

Joint Analysis of Single-Cell Data across Cohorts with Missing Modalities

Joint analysis of multi-omic single-cell data across cohorts has significantly enhanced the comprehensive analysis of cellular processes. However, most of the existing approaches for this purpose require access to samples with complete modality availability, which is impractical in many real-world scenarios. In this paper, we propose (Single-Cell Cross-Cohort Cross-Category) integration, a novel framework that learns unified cell representations under domain shift without requiring full-modality reference samples. Our generative approach learns rich cross-modal and cross-domain relationships that enable imputation of these missing modalities. Through experiments on real-world multi-omic datasets, we demonstrate that offers a robust solution to single-cell tasks such as cell type clustering, cell type classification, and feature imputation.

Local Discovery by Partitioning: Polynomial-Time Causal Discovery Around Exposure-Outcome Pairs

This work addresses the problem of automated covariate selection under limited prior knowledge. Given an exposure-outcome pair {X,Y} and a variable set Z of unknown causal structure, the Local Discovery by Partitioning (LDP) algorithm partitions Z into subsets defined by their relation to {X,Y}. We enumerate eight exhaustive and mutually exclusive partitions of any arbitrary Z and leverage this taxonomy to differentiate confounders from other variable types. LDP is motivated by valid adjustment set identification, but avoids the pretreatment assumption commonly made by automated covariate selection methods. We provide theoretical guarantees that LDP returns a valid adjustment set for any Z that meets sufficient graphical conditions. Under stronger conditions, we prove that partition labels are asymptotically correct. Total independence tests is worst-case quadratic in |Z|, with sub-quadratic runtimes observed empirically. We numerically validate our theoretical guarantees on synthetic and semi-synthetic graphs. Adjustment sets from LDP yield less biased and more precise average treatment effect estimates than baselines, with LDP outperforming on confounder recall, test count, and runtime for valid adjustment set discovery.

Bipartite Ranking Fairness through a Model Agnostic Ordering Adjustment

Algorithmic fairness has been a serious concern and received lots of interest in machine learning community. In this paper, we focus on the bipartite ranking scenario, where the instances come from either the positive or negative class and the goal is to learn a ranking function that ranks positive instances higher than negative ones. While there could be a trade-off between fairness and performance, we propose a model agnostic post-processing framework xOrder for achieving fairness in bipartite ranking and maintaining the algorithm classification performance. In particular, we optimize a weighted sum of the utility as identifying an optimal warping path across different protected groups and solve it through a dynamic programming process. xOrder is compatible with various classification models and ranking fairness metrics, including supervised and unsupervised fairness metrics. In addition to binary groups, xOrder can be applied to multiple protected groups. We evaluate our proposed algorithm on four benchmark data sets and two real-world patient electronic health record repositories. xOrder consistently achieves a better balance between the algorithm utility and ranking fairness on a variety of datasets with different metrics. From the visualization of the calibrated ranking scores, xOrder mitigates the score distribution shifts of different groups compared with baselines. Moreover, additional analytical results verify that xOrder achieves a robust performance when faced with fewer samples and a bigger difference between training and testing ranking score distributions.

InfoDiffusion: Representation Learning Using Information Maximizing Diffusion Models

While diffusion models excel at generating high-quality samples, their latent variables typically lack semantic meaning and are not suitable for representation learning. Here, we propose InfoDiffusion, an algorithm that augments diffusion models with low-dimensional latent variables that capture high-level factors of variation in the data. InfoDiffusion relies on a learning objective regularized with the mutual information between observed and hidden variables, which improves latent space quality and prevents the latents from being ignored by expressive diffusion-based decoders. Empirically, we find that InfoDiffusion learns disentangled and human-interpretable latent representations that are competitive with state-of-the-art generative and contrastive methods, while retaining the high sample quality of diffusion models. Our method enables manipulating the attributes of generated images and has the potential to assist tasks that require exploring a learned latent space to generate quality samples, e.g., generative design.

Patchwork Learning: A Paradigm Towards Integrative Analysis across Diverse Biomedical Data Sources

Machine learning (ML) in healthcare presents numerous opportunities for enhancing patient care, population health, and healthcare providers' workflows. However, the real-world clinical and cost benefits remain limited due to challenges in data privacy, heterogeneous data sources, and the inability to fully leverage multiple data modalities. In this perspective paper, we introduce "patchwork learning" (PL), a novel paradigm that addresses these limitations by integrating information from disparate datasets composed of different data modalities (e.g., clinical free-text, medical images, omics) and distributed across separate and secure sites. PL allows the simultaneous utilization of complementary data sources while preserving data privacy, enabling the development of more holistic and generalizable ML models. We present the concept of patchwork learning and its current implementations in healthcare, exploring the potential opportunities and applicable data sources for addressing various healthcare challenges. PL leverages bridging modalities or overlapping feature spaces across sites to facilitate information sharing and impute missing data, thereby addressing related prediction tasks. We discuss the challenges associated with PL, many of which are shared by federated and multimodal learning, and provide recommendations for future research in this field. By offering a more comprehensive approach to healthcare data integration, patchwork learning has the potential to revolutionize the clinical applicability of ML models. This paradigm promises to strike a balance between personalization and generalizability, ultimately enhancing patient experiences, improving population health, and optimizing healthcare providers' workflows.

Correcting the User Feedback-Loop Bias for Recommendation Systems

Selection bias is prevalent in the data for training and evaluating recommendation systems with explicit feedback. For example, users tend to rate items they like. However, when rating an item concerning a specific user, most of the recommendation algorithms tend to rely too much on his/her rating (feedback) history. This introduces implicit bias on the recommendation system, which is referred to as user feedback-loop bias in this paper. We propose a systematic and dynamic way to correct such bias and to obtain more diverse and objective recommendations by utilizing temporal rating information. Specifically, our method includes a deep-learning component to learn each user's dynamic rating history embedding for the estimation of the probability distribution of the items that the user rates sequentially. These estimated dynamic exposure probabilities are then used as propensity scores to train an inverse-propensity-scoring (IPS) rating predictor. We empirically validated the existence of such user feedback-loop bias in real world recommendation systems and compared the performance of our method with the baseline models that are either without de-biasing or with propensity scores estimated by other methods. The results show the superiority of our approach.

Learning to Collaborate

In this paper, we focus on effective learning over a collaborative research network involving multiple clients. Each client has its own sample population which may not be shared with other clients due to privacy concerns. The goal is to learn a model for each client, which behaves better than the one learned from its own data, through secure collaborations with other clients in the network. Due to the discrepancies of the sample distributions across different clients, it is not necessarily that collaborating with everyone will lead to the best local models. We propose a learning to collaborate framework, where each client can choose to collaborate with certain members in the network to achieve a "collaboration equilibrium", where smaller collaboration coalitions are formed within the network so that each client can obtain the model with the best utility. We propose the concept of benefit graph which describes how each client can benefit from collaborating with other clients and develop a Pareto optimization approach to obtain it. Finally the collaboration coalitions can be derived from it based on graph operations. Our framework provides a new way of setting up collaborations in a research network. Experiments on both synthetic and real world data sets are provided to demonstrate the effectiveness of our method.

Fair and Consistent Federated Learning

Federated learning (FL) has gain growing interests for its capability of learning from distributed data sources collectively without the need of accessing the raw data samples across different sources. So far FL research has mostly focused on improving the performance, how the algorithmic disparity will be impacted for the model learned from FL and the impact of algorithmic disparity on the utility inconsistency are largely unexplored. In this paper, we propose an FL framework to jointly consider performance consistency and algorithmic fairness across different local clients (data sources). We derive our framework from a constrained multi-objective optimization perspective, in which we learn a model satisfying fairness constraints on all clients with consistent performance. Specifically, we treat the algorithm prediction loss at each local client as an objective and maximize the worst-performing client with fairness constraints through optimizing a surrogate maximum function with all objectives involved. A gradient-based procedure is employed to achieve the Pareto optimality of this optimization problem. Theoretical analysis is provided to prove that our method can converge to a Pareto solution that achieves the min-max performance with fairness constraints on all clients. Comprehensive experiments on synthetic and real-world datasets demonstrate the superiority that our approach over baselines and its effectiveness in achieving both fairness and consistency across all local clients.

Explaining Algorithmic Fairness Through Fairness-Aware Causal Path Decomposition

Algorithmic fairness has aroused considerable interests in data mining and machine learning communities recently. So far the existing research has been mostly focusing on the development of quantitative metrics to measure algorithm disparities across different protected groups, and approaches for adjusting the algorithm output to reduce such disparities. In this paper, we propose to study the problem of identification of the source of model disparities. Unlike existing interpretation methods which typically learn feature importance, we consider the causal relationships among feature variables and propose a novel framework to decompose the disparity into the sum of contributions from fairness-aware causal paths, which are paths linking the sensitive attribute and the final predictions, on the graph. We also consider the scenario when the directions on certain edges within those paths cannot be determined. Our framework is also model agnostic and applicable to a variety of quantitative disparity measures. Empirical evaluations on both synthetic and real-world data sets are provided to show that our method can provide precise and comprehensive explanations to the model disparities.