Large Language Models (LLMs) have shown strong promise for mining Electronic Health Records (EHRs) by reasoning over longitudinal clinical information to capture context-rich patient trajectories. However, leveraging LLMs for structured EHRs (e.g., standardized diagnosis and medication codes) presents two key challenges. First, translating time-stamped EHR sequences into plain text can obscure both temporal structure and code identities, weakening the ability to capture code co-occurrence and longitudinal regularities. Second, unlike cohort-trained predictive models that learn a shared, task-aligned representation space across patients, LLMs are often applied in a case-isolated inference setting where each patient is processed independently without leveraging population-level patterns. To address these challenges, we introduce RePrompT, a time-aware LLM framework that integrates structured EHR encoders through prompt tuning, without modifying underlying architectures. Specifically, RePrompT recurrently incorporates latent states from prior visits to preserve longitudinal information, and injects population-level information through trainable prompt tokens derived from a cohort-trained, task-aligned EHR encoder. Experiments on MIMIC-III and MIMIC-IV demonstrate that RePrompT consistently outperforms both EHR-based and LLM-based baselines across multiple clinical prediction tasks.

Learning rich medical concept representations is essential for EHR prediction. Text-attributed knowledge graphs (TKGs) provide a natural foundation by organizing heterogeneous medical relations together with textual semantics. However, most existing encoders process concepts uniformly across patients, despite the fact that a code’s meaning and predictive value depend on patient-specific clinical context and trajectory. Learning patient-personalized concept representations from TKGs introduces two key challenges: (1) deciding how much KG context to incorporate for each observed code, and (2) aligning semantic information with the patient-specific relational structure. We propose REFINE, a KG-aware budgeted LLM graph refinement framework for patient-personalized medical concept encoding. Starting from a global TKG, REFINE constructs patient-specific temporal graphs. A sequential reinforcement learning policy selects a personalized KG expansion budget for each observed code. The resulting patient graph is processed by a heterogeneous GNN to capture relation-aware structural dependencies, while a frozen LLM uses graph-aware soft prompts to semantically refine concept representations. Experiments on MIMIC-III and MIMIC-IV show that REFINE consistently improves diverse EHR backbones, outperforms strong baselines, and demonstrates robust gains across component ablation, KG selection, and data insufficiency.

Unstructured discharge notes in Electronic Health Records (EHRs) often carry signal complementary to structured medical codes, holding patient-specific evidence that standardized cohort-level codes alone cannot capture. However, this evidence in notes is frequently buried in lengthy, noisy text that is not intentionally written with any specific clinical prediction in mind. Summarization is an obvious mitigation, but generic summaries, tuned for fluency rather than the outcome, routinely omit decisive evidence while retaining plausible but uninformative detail. To this end, we propose RASPER, a Reward-Aligned Summarizer for Prediction in EHR, that optimizes note summarization directly against the downstream clinical task. RASPER employs a tunable LLM-based summarizer to extract task-relevant evidence from discharge notes and trains it via reinforcement learning from prediction feedback, using a reward derived from the downstream predictor’s loss. To ground the summarizer, a longitudinal encoder converts structured codes into soft prompts that incorporate each patient’s clinical context into note summarization. By rewarding the quality of the resulting multimodal prediction, RASPER encourages the summarizer to retain patient-specific evidence that complements, rather than duplicates, information captured by structured codes. RASPER consistently outperforms strong baselines on both readmission prediction and medication recommendation across MIMIC-III and MIMIC-IV.

Gene set analysis is a cornerstone of functional genomics, yet it remains labor-intensive and heavily dependent on manual curation and expert biological interpretation. While Large Language Models (LLMs) have emerged as powerful tools for genomic reasoning and annotation, most existing approaches rely on symbolic gene names and fail to capture domain-specific biological structure, particularly protein sequence information that governs molecular activity, interactions, and downstream gene function. In this work, we propose SoftGene, a novel framework for LLM-based gene set annotation that leverages the hierarchical structure of gene sets. First, we use a hierarchical attention-based encoder built on ESM, a protein language model, to represent each gene set using protein-level amino acid sequence information. Second, we construct a hybrid prompting scheme that combines soft prompts derived from gene set embeddings with hard prompts containing auxiliary context generated by an LLM, and feed the resulting prompt into a local LLM for annotation. We evaluate our framework on two benchmark datasets: Gene Ontology (GO) and the Molecular Signatures Database (MSigDB). Our results show that integrating protein-sequence representations with textual context improves gene set annotation overall, while per-domain analyses reveal that the contribution of protein embeddings varies across biological domains.

Longitudinal prediction from electronic health records (EHRs) is limited by the sparsity and irregularity in patient trajectories, and knowledge augmentation with external knowledge graphs (KGs) offers a promising way to alleviate these issues. However, most existing methods perform fixed, context-agnostic topology augmentation by adding the same KG nodes and edges regardless of a patient’s evolving state. We propose ReTA, a Reinforcement learning-based dynamic Topology Augmentation framework that casts KG import as a per-visit, budget-aware policy. ReTA first constructs an offline refined pool of KG-grounded templates, then learns a policy to select one augment action per visit from three options: Soft Import, which enriches node features without modifying graph topology, Hard Import, which grafts a compact KG subgraph onto the visit graph to create message-passing shortcuts, and Skip, which leaves the visit unaugmented when the base encoder is already confident. To stabilize learning, ReTA employs a decoupled encoder that processes semantic and structural signals in separate channels and fuses them via adaptive gating. Experiments on MIMIC-III and MIMIC-IV across diagnosis prediction, mortality, and readmission show that ReTA consistently outperforms strong baselines while remaining efficient, transfers across datasets and knowledge graphs, and yields interpretable augmentation patterns. The robust gains under sparse supervision highlight the advantage of ReTA’s dynamic decision to import knowledge, boosting accuracy while curbing costs.

In electronic health record (EHR) mining, learning high-quality representations of medical concepts (e.g., standardized diagnosis, medication, and procedure codes) is fundamental for downstream clinical prediction. However, robust concept representation learning is hindered by two key challenges: (i) clinically important cross-type dependencies (e.g., diagnosis-medication and medication-procedure relations) are often missing or incomplete in existing ontology resources, limiting the ability to model complex EHR patterns; and (ii) rich clinical semantics are often missing from structured resources, and even when available as text, are difficult to integrate with KG structure for representation learning. To address these challenges, we present MedCo, an LLM-empowered graph learning framework for medical concept representation. MedCo first builds a global knowledge graph (KG) over medical codes by combining statistically reliable associations mined from EHRs with type-constrained LLM prompting to infer semantic relations. It then utilizes LLMs to enrich the KG into a text-attributed graph by generating node descriptions and edge rationales, providing semantic signals for both concepts and their relationships. Finally, MedCo jointly trains a LoRA-tuned LLaMA text encoder with a heterogeneous GNN, fusing text semantics and graph structure into unified concept embeddings. Extensive experiments on MIMIC-III and MIMIC-IV show that MedCo consistently improves prediction performance and serves as an effective plug-in concept encoder for standard EHR pipelines.