Huan He

Huan He, Owen Queen, Teddy Koker et al. · mit

Unsupervised domain adaptation (UDA) enables the transfer of models trained on source domains to unlabeled target domains. However, transferring complex time series models presents challenges due to the dynamic temporal structure variations across domains. This leads to feature shifts in the time and frequency representations. Additionally, the label distributions of tasks in the source and target domains can differ significantly, posing difficulties in addressing label shifts and recognizing labels unique to the target domain. Effectively transferring complex time series models remains a formidable problem. We present Raincoat, the first model for both closed-set and universal domain adaptation on complex time series. Raincoat addresses feature and label shifts by considering both temporal and frequency features, aligning them across domains, and correcting for misalignments to facilitate the detection of private labels. Additionally, Raincoat improves transferability by identifying label shifts in target domains. Our experiments with 5 datasets and 13 state-of-the-art UDA methods demonstrate that Raincoat can improve transfer learning performance by up to 16.33% and can handle both closed-set and universal domain adaptation.

Brian Ondov, Chia-Hsuan Chang, Weipeng Zhou et al.

High-dimensional biomedical data, such as cell-by-gene matrices, are increasingly generated temporally. However, Manifold Learning algorithms, like t-SNE and UMAP, cannot incorporate time-ordering in their layouts, obfuscating the dynamics of cell types or other classes. As a solution, we present IRIS, a new Manifold Learning algorithm that structures layouts both chronologically and by manifold topology. IRIS can visualize a wide range of dynamic biomedical data, including scRNA-seq, comparative metagenomics, and literature.

Owen Queen, Thomas Hartvigsen, Teddy Koker et al. · mit

Interpreting time series models is uniquely challenging because it requires identifying both the location of time series signals that drive model predictions and their matching to an interpretable temporal pattern. While explainers from other modalities can be applied to time series, their inductive biases do not transfer well to the inherently challenging interpretation of time series. We present TimeX, a time series consistency model for training explainers. TimeX trains an interpretable surrogate to mimic the behavior of a pretrained time series model. It addresses the issue of model faithfulness by introducing model behavior consistency, a novel formulation that preserves relations in the latent space induced by the pretrained model with relations in the latent space induced by TimeX. TimeX provides discrete attribution maps and, unlike existing interpretability methods, it learns a latent space of explanations that can be used in various ways, such as to provide landmarks to visually aggregate similar explanations and easily recognize temporal patterns. We evaluate TimeX on eight synthetic and real-world datasets and compare its performance against state-of-the-art interpretability methods. We also conduct case studies using physiological time series. Quantitative evaluations demonstrate that TimeX achieves the highest or second-highest performance in every metric compared to baselines across all datasets. Through case studies, we show that the novel components of TimeX show potential for training faithful, interpretable models that capture the behavior of pretrained time series models.

Jiali Cheng, George Dasoulas, Huan He et al. · harvard

Graph unlearning, which involves deleting graph elements such as nodes, node labels, and relationships from a trained graph neural network (GNN) model, is crucial for real-world applications where data elements may become irrelevant, inaccurate, or privacy-sensitive. However, existing methods for graph unlearning either deteriorate model weights shared across all nodes or fail to effectively delete edges due to their strong dependence on local graph neighborhoods. To address these limitations, we introduce GNNDelete, a novel model-agnostic layer-wise operator that optimizes two critical properties, namely, Deleted Edge Consistency and Neighborhood Influence, for graph unlearning. Deleted Edge Consistency ensures that the influence of deleted elements is removed from both model weights and neighboring representations, while Neighborhood Influence guarantees that the remaining model knowledge is preserved after deletion. GNNDelete updates representations to delete nodes and edges from the model while retaining the rest of the learned knowledge. We conduct experiments on seven real-world graphs, showing that GNNDelete outperforms existing approaches by up to 38.8% (AUC) on edge, node, and node feature deletion tasks, and 32.2% on distinguishing deleted edges from non-deleted ones. Additionally, GNNDelete is efficient, taking 12.3x less time and 9.3x less space than retraining GNN from scratch on WordNet18.

Huan He, Shifan Zhao, Ziyuan Tang et al.

Nonlinear acceleration methods are powerful techniques to speed up fixed-point iterations. However, many acceleration methods require storing a large number of previous iterates and this can become impractical if computational resources are limited. In this paper, we propose a nonlinear Truncated Generalized Conjugate Residual method (nlTGCR) whose goal is to exploit the symmetry of the Hessian to reduce memory usage. The proposed method can be interpreted as either an inexact Newton or a quasi-Newton method. We show that, with the help of global strategies like residual check techniques, nlTGCR can converge globally for general nonlinear problems and that under mild conditions, nlTGCR is able to achieve superlinear convergence. We further analyze the convergence of nlTGCR in a stochastic setting. Numerical results demonstrate the superiority of nlTGCR when compared with several other competitive baseline approaches on a few problems. Our code will be available in the future.

Huan He, Shifan Zhao, Yuanzhe Xi et al.

Due to patient privacy protection concerns, machine learning research in healthcare has been undeniably slower and limited than in other application domains. High-quality, realistic, synthetic electronic health records (EHRs) can be leveraged to accelerate methodological developments for research purposes while mitigating privacy concerns associated with data sharing. The current state-of-the-art model for synthetic EHR generation is generative adversarial networks, which are notoriously difficult to train and can suffer from mode collapse. Denoising Diffusion Probabilistic Models, a class of generative models inspired by statistical thermodynamics, have recently been shown to generate high-quality synthetic samples in certain domains. It is unknown whether these can generalize to generation of large-scale, high-dimensional EHRs. In this paper, we present a novel generative model based on diffusion models that is the first successful application on electronic health records. Our model proposes a mechanism to perform class-conditional sampling to preserve label information. We also introduce a new sampling strategy to accelerate the inference speed. We empirically show that our model outperforms existing state-of-the-art synthetic EHR generation methods.

Yingchun Guo, Huan He, Ye Zhu et al.

Domain generalization person re-identification (DG Re-ID) aims to directly deploy a model trained on the source domain to the unseen target domain with good generalization, which is a challenging problem and has practical value in a real-world deployment. In the existing DG Re-ID methods, invariant operations are effective in extracting domain generalization features, and Instance Normalization (IN) or Batch Normalization (BN) is used to alleviate the bias to unseen domains. Due to domain-specific information being used to capture discriminability of the individual source domain, the generalized ability for unseen domains is unsatisfactory. To address this problem, an Attention-aware Multi-operation Strategery (AMS) for DG Re-ID is proposed to extract more generalized features. We investigate invariant operations and construct a multi-operation module based on IN and group whitening (GW) to extract domain-invariant feature representations. Furthermore, we analyze different domain-invariant characteristics, and apply spatial attention to the IN operation and channel attention to the GW operation to enhance the domain-invariant features. The proposed AMS module can be used as a plug-and-play module to incorporate into existing network architectures. Extensive experimental results show that AMS can effectively enhance the model's generalization ability to unseen domains and significantly improves the recognition performance in DG Re-ID on three protocols with ten datasets.

Difeng Cai, Yuliang Ji, Huan He et al.

Nonlinear monotone transformations are used extensively in normalizing flows to construct invertible triangular mappings from simple distributions to complex ones. In existing literature, monotonicity is usually enforced by restricting function classes or model parameters and the inverse transformation is often approximated by root-finding algorithms as a closed-form inverse is unavailable. In this paper, we introduce a new integral-based approach termed "Atomic Unrestricted Time Machine (AUTM)", equipped with unrestricted integrands and easy-to-compute explicit inverse. AUTM offers a versatile and efficient way to the design of normalizing flows with explicit inverse and unrestricted function classes or parameters. Theoretically, we present a constructive proof that AUTM is universal: all monotonic normalizing flows can be viewed as limits of AUTM flows. We provide a concrete example to show how to approximate any given monotonic normalizing flow using AUTM flows with guaranteed convergence. The result implies that AUTM can be used to transform an existing flow into a new one equipped with explicit inverse and unrestricted parameters. The performance of the new approach is evaluated on high dimensional density estimation, variational inference and image generation. Experiments demonstrate superior speed and memory efficiency of AUTM.

Ru Huang, Kai Chang, Huan He et al.

We propose a data-driven and machine-learning-based approach to compute non-Galerkin coarse-grid operators in algebraic multigrid (AMG) methods, addressing the well-known issue of increasing operator complexity. Guided by the AMG theory on spectrally equivalent coarse-grid operators, we have developed novel ML algorithms that utilize neural networks (NNs) combined with smooth test vectors from multigrid eigenvalue problems. The proposed method demonstrates promise in reducing the complexity of coarse-grid operators while maintaining overall AMG convergence for solving parametric partial differential equation (PDE) problems. Numerical experiments on anisotropic rotated Laplacian and linear elasticity problems are provided to showcase the performance and compare with existing methods for computing non-Galerkin coarse-grid operators.

Lingfei Qian, Mauro Giuffre, Yan Wang et al.

Clinical decision-making increasingly relies on timely and context-aware access to patient information within Electronic Health Records (EHRs), yet most existing natural language question-answering (QA) systems are evaluated solely on benchmark datasets, limiting their practical relevance. To overcome this limitation, we introduce EHRNavigator, a multi-agent framework that harnesses AI agents to perform patient-level question answering across heterogeneous and multimodal EHR data. We assessed its performance using both public benchmark and institutional datasets under realistic hospital conditions characterized by diverse schemas, temporal reasoning demands, and multimodal evidence integration. Through quantitative evaluation and clinician-validated chart review, EHRNavigator demonstrated strong generalization, achieving 86% accuracy on real-world cases while maintaining clinically acceptable response times. Overall, these findings confirm that EHRNavigator effectively bridges the gap between benchmark evaluation and clinical deployment, offering a robust, adaptive, and efficient solution for real-world EHR question answering.

Qianqian Xie, Qingyu Chen, Aokun Chen et al.

Recent advancements in large language models (LLMs) like ChatGPT and LLaMA show promise in medical applications, yet challenges remain in medical language comprehension. This study presents Me-LLaMA, a new medical LLM family based on open-source LLaMA models, optimized for medical text analysis and diagnosis by leveraging large-scale, domain-specific datasets. The Me-LLaMA family, including foundation models Me-LLaMA 13/70B and their chat-enhanced versions, was developed through continued pre-training and instruction tuning with 129B tokens and 214K samples from biomedical and clinical sources. Training the 70B models required over 100,000 A100 GPU hours. Me-LLaMA's performance was evaluated across six medical text analysis tasks using 12 benchmark datasets and complex clinical case diagnosis, with automatic and human evaluations. Results indicate Me-LLaMA outperforms LLaMA and other open-source medical LLMs in zero-shot and supervised settings. Task-specific tuning further boosts performance, surpassing ChatGPT on 7 of 8 datasets and GPT-4 on 5 of 8. For complex clinical cases, Me-LLaMA achieves performance comparable to ChatGPT and GPT-4. This work underscores the importance of domain-specific data in developing medical LLMs and addresses the high computational costs involved in training, highlighting a balance between pre-training and fine-tuning strategies. Me-LLaMA models are now accessible under user agreements, providing a valuable resource for advancing medical AI.

Xueqing Peng, Zhuohan Xie, Yupeng Cao et al.

As AI agents improve, the central question is no longer whether they can solve isolated well-defined financial tasks, but whether they can reliably carry out financial professional work. Existing financial benchmarks offer only a partial view of this ability, as they primarily evaluate static competencies such as question answering, retrieval, summarization, and classification. We introduce Herculean, the first skilled benchmark for agentic financial intelligence spanning four representative workflows, including Trading, Hedging, Market Insights, and Auditing. Each workflow is instantiated as a standardized MCP-based skill environment with its own tools, interaction dynamics, constraints, and success criteria, enabling consistent end-to-end assessment of heterogeneous agent systems. Across frontier agents, we find agents perform relatively well on Trading and Market Insights, but struggle substantially on Hedging and Auditing, where long-horizon coordination, state consistency, and structured verification are critical. Overall, our results point to a key gap in current agents in turning financial reasoning into dependable workflow execution in high-stakes financial workflows.

Qingyu Chen, Yan Hu, Xueqing Peng et al.

The rapid growth of biomedical literature poses challenges for manual knowledge curation and synthesis. Biomedical Natural Language Processing (BioNLP) automates the process. While Large Language Models (LLMs) have shown promise in general domains, their effectiveness in BioNLP tasks remains unclear due to limited benchmarks and practical guidelines. We perform a systematic evaluation of four LLMs, GPT and LLaMA representatives on 12 BioNLP benchmarks across six applications. We compare their zero-shot, few-shot, and fine-tuning performance with traditional fine-tuning of BERT or BART models. We examine inconsistencies, missing information, hallucinations, and perform cost analysis. Here we show that traditional fine-tuning outperforms zero or few shot LLMs in most tasks. However, closed-source LLMs like GPT-4 excel in reasoning-related tasks such as medical question answering. Open source LLMs still require fine-tuning to close performance gaps. We find issues like missing information and hallucinations in LLM outputs. These results offer practical insights for applying LLMs in BioNLP.

Fan Ma, Yuntian Liu, Xiang Lan et al.

Evidence derived from large-scale real-world data (RWD) is increasingly informing regulatory evaluation and healthcare decision-making. Administrative claims provide population-scale, longitudinal records of healthcare utilization, expenditure, and detailed coding of diagnoses, procedures, and medications, yet their potential as a substrate for healthcare foundation models remains largely unexplored. Here we present ReClaim, a generative transformer trained from scratch on 43.8 billion medical events from more than 200 million enrollees in the MarketScan claims data spanning 2008-2022. ReClaim models longitudinal trajectories across diagnoses, procedures, medications, and expenditure, and was scaled to 140 million, 700 million, and 1.7 billion parameters. Across over 1,000 disease-onset prediction tasks, ReClaim achieved a mean AUC of 75.6%, substantially outperforming disease-specific LightGBM (66.3%) and the transformer-based Delphi model (69.4%), with the largest gains for rare diseases. These advantages held across retrospective and prospective evaluations and in external validation on two independent datasets. Performance improved monotonically with scale, and post-training added 13.8 percentage points over pre-training alone. Beyond disease prediction, ReClaim captured financial outcomes and improved real-world evidence (RWE) analyses: for healthcare expenditure forecasting it increased explained variance from 0.28 to 0.37 relative to LightGBM, and in a target trial emulation it reduced systematic bias by 72% on average relative to Delphi. Together, these results establish administrative claims as a scalable substrate for healthcare foundation models and show that learned representations generalize across time periods and data sources, supporting disease surveillance, expenditure forecasting, and RWE generation.

Weihai Lu, Zhejun Zhao, Yanshu Li et al.

Multimodal Stance Detection (MSD) is crucial for understanding public discourse, yet effectively fusing text and image, especially with conflicting signals, remains challenging. Existing methods often face difficulties with contextual grounding, cross-modal interpretation ambiguity, and single-pass reasoning fragility. To address these, we propose Retrieval-Augmented Multi-modal Multi-agent Stance Detection (MM-StanceDet), a novel multi-agent framework integrating Retrieval Augmentation for contextual grounding, specialized Multimodal Analysis agents for nuanced interpretation, a Reasoning-Enhanced Debate stage for exploring perspectives, and Self-Reflection for robust adjudication. Extensive experiments on five datasets demonstrate MM-StanceDet significantly outperforms state-of-the-art baselines, validating the efficacy of its multi-agent architecture and structured reasoning stages in addressing complex multimodal stance challenges.

Xueqing Peng, Lingfei Qian, Yan Wang et al.

Real-world financial analysis involves information across multiple languages and modalities, from reports and news to scanned filings and meeting recordings. Yet most existing evaluations of LLMs in finance remain text-only, monolingual, and largely saturated by current models. To bridge these gaps, we present MultiFinBen, the first expert-annotated multilingual (five languages) and multimodal (text, vision, audio) benchmark for evaluating LLMs in realistic financial contexts. MultiFinBen introduces two new task families: multilingual financial reasoning, which tests cross-lingual evidence integration from filings and news, and financial OCR, which extracts structured text from scanned documents containing tables and charts. Rather than aggregating all available datasets, we apply a structured, difficulty-aware selection based on advanced model performance, ensuring balanced challenge and removing redundant tasks. Evaluating 21 leading LLMs shows that even frontier multimodal models like GPT-4o achieve only 46.01% overall, stronger on vision and audio but dropping sharply in multilingual settings. These findings expose persistent limitations in multilingual, multimodal, and expert-level financial reasoning. All datasets, evaluation scripts, and leaderboards are publicly released.

Rongbin Li, Wenbo Chen, Zhao Li et al.

Single-cell RNA sequencing has transformed our ability to identify diverse cell types and their transcriptomic signatures. However, annotating these signatures-especially those involving poorly characterized genes-remains a major challenge. Traditional methods, such as Gene Set Enrichment Analysis (GSEA), depend on well-curated annotations and often perform poorly in these contexts. Large Language Models (LLMs) offer a promising alternative but struggle to represent complex biological knowledge within structured ontologies. To address this, we present BRAINCELL-AID (BRAINCELL-AID: https://biodataai.uth.edu/BRAINCELL-AID), a novel multi-agent AI system that integrates free-text descriptions with ontology labels to enable more accurate and robust gene set annotation. By incorporating retrieval-augmented generation (RAG), we developed a robust agentic workflow that refines predictions using relevant PubMed literature, reducing hallucinations and enhancing interpretability. Using this workflow, we achieved correct annotations for 77% of mouse gene sets among their top predictions. Applying this approach, we annotated 5,322 brain cell clusters from the comprehensive mouse brain cell atlas generated by the BRAIN Initiative Cell Census Network, enabling novel insights into brain cell function by identifying region-specific gene co-expression patterns and inferring functional roles of gene ensembles. BRAINCELL-AID also identifies Basal Ganglia-related cell types with neurologically meaningful descriptions. Hence, we create a valuable resource to support community-driven cell type annotation.

Lingfei Qian, Xueqing Peng, Yan Wang et al.

Although Large Language Model (LLM)-based agents are increasingly used in financial trading, it remains unclear whether they can reason and adapt in live markets, as most studies test models instead of agents, cover limited periods and assets, and rely on unverified data. To address these gaps, we introduce Agent Market Arena (AMA), the first lifelong, real-time benchmark for evaluating LLM-based trading agents across multiple markets. AMA integrates verified trading data, expert-checked news, and diverse agent architectures within a unified trading framework, enabling fair and continuous comparison under real conditions. It implements four agents, including InvestorAgent as a single-agent baseline, TradeAgent and HedgeFundAgent with different risk styles, and DeepFundAgent with memory-based reasoning, and evaluates them across GPT-4o, GPT-4.1, Claude-3.5-haiku, Claude-sonnet-4, and Gemini-2.0-flash. Live experiments on both cryptocurrency and stock markets demonstrate that agent frameworks display markedly distinct behavioral patterns, spanning from aggressive risk-taking to conservative decision-making, whereas model backbones contribute less to outcome variation. AMA thus establishes a foundation for rigorous, reproducible, and continuously evolving evaluation of financial reasoning and trading intelligence in LLM-based agents.

Lu Li, Tianyu Zhang, Zhiqi Bu et al.

Model merging has emerged as an effective approach to combine multiple single-task models into a multitask model. This process typically involves computing a weighted average of the model parameters without any additional training. Existing model-merging methods focus on enhancing average task accuracy. However, interference and conflicts between the objectives of different tasks can lead to trade-offs during the merging process. In real-world applications, a set of solutions with various trade-offs can be more informative, helping practitioners make decisions based on diverse preferences. In this paper, we introduce a novel and low-compute algorithm, Model Merging with Amortized Pareto Front (MAP). MAP efficiently identifies a Pareto set of scaling coefficients for merging multiple models, reflecting the trade-offs involved. It amortizes the substantial computational cost of evaluations needed to estimate the Pareto front by using quadratic approximation surrogate models derived from a pre-selected set of scaling coefficients. Experimental results on vision and natural language processing tasks demonstrate that MAP can accurately identify the Pareto front, providing practitioners with flexible solutions to balance competing task objectives. We also introduce Bayesian MAP for scenarios with a relatively low number of tasks and Nested MAP for situations with a high number of tasks, further reducing the computational cost of evaluation.

Sungrim Moon, Huan He, Hongfang Liu et al.

Background: Extractive question-answering (EQA) is a useful natural language processing (NLP) application for answering patient-specific questions by locating answers in their clinical notes. Realistic clinical EQA can have multiple answers to a single question and multiple focus points in one question, which are lacking in the existing datasets for development of artificial intelligence solutions. Objective: Create a dataset for developing and evaluating clinical EQA systems that can handle natural multi-answer and multi-focus questions. Methods: We leveraged the annotated relations from the 2018 National NLP Clinical Challenges (n2c2) corpus to generate an EQA dataset. Specifically, the 1-to-N, M-to-1, and M-to-N drug-reason relations were included to form the multi-answer and multi-focus QA entries, which represent more complex and natural challenges in addition to the basic one-drug-one-reason cases. A baseline solution was developed and tested on the dataset. Results: The derived RxWhyQA dataset contains 96,939 QA entries. Among the answerable questions, 25% require multiple answers, and 2% ask about multiple drugs within one question. There are frequent cues observed around the answers in the text, and 90% of the drug and reason terms occur within the same or an adjacent sentence. The baseline EQA solution achieved a best f1-measure of 0.72 on the entire dataset, and on specific subsets, it was: 0.93 on the unanswerable questions, 0.48 on single-drug questions versus 0.60 on multi-drug questions, 0.54 on the single-answer questions versus 0.43 on multi-answer questions. Discussion: The RxWhyQA dataset can be used to train and evaluate systems that need to handle multi-answer and multi-focus questions. Specifically, multi-answer EQA appears to be challenging and therefore warrants more investment in research.

Sijia Liu, Andrew Wen, Liwei Wang et al.

While we pay attention to the latest advances in clinical natural language processing (NLP), we can notice some resistance in the clinical and translational research community to adopt NLP models due to limited transparency, interpretability, and usability. In this study, we proposed an open natural language processing development framework. We evaluated it through the implementation of NLP algorithms for the National COVID Cohort Collaborative (N3C). Based on the interests in information extraction from COVID-19 related clinical notes, our work includes 1) an open data annotation process using COVID-19 signs and symptoms as the use case, 2) a community-driven ruleset composing platform, and 3) a synthetic text data generation workflow to generate texts for information extraction tasks without involving human subjects. The corpora were derived from texts from three different institutions (Mayo Clinic, University of Kentucky, University of Minnesota). The gold standard annotations were tested with a single institution's (Mayo) ruleset. This resulted in performances of 0.876, 0.706, and 0.694 in F-scores for Mayo, Minnesota, and Kentucky test datasets, respectively. The study as a consortium effort of the N3C NLP subgroup demonstrates the feasibility of creating a federated NLP algorithm development and benchmarking platform to enhance multi-institution clinical NLP study and adoption. Although we use COVID-19 as a use case in this effort, our framework is general enough to be applied to other domains of interest in clinical NLP.

Huan He, Shifan Zhao, Yuanzhe Xi et al.

Many modern machine learning algorithms such as generative adversarial networks (GANs) and adversarial training can be formulated as minimax optimization. Gradient descent ascent (GDA) is the most commonly used algorithm due to its simplicity. However, GDA can converge to non-optimal minimax points. We propose a new minimax optimization framework, GDA-AM, that views the GDAdynamics as a fixed-point iteration and solves it using Anderson Mixing to con-verge to the local minimax. It addresses the diverging issue of simultaneous GDAand accelerates the convergence of alternating GDA. We show theoretically that the algorithm can achieve global convergence for bilinear problems under mild conditions. We also empirically show that GDA-AMsolves a variety of minimax problems and improves GAN training on several datasets

Lei Wang, Shihui Zhang, Huan He et al.

With the widespread use of touch-screen devices, it is more and more convenient for people to draw sketches on screen. This results in the demand for automatically understanding the sketches. Thus, the sketch recognition task becomes more significant than before. To accomplish this task, it is necessary to solve the critical issue of improving the distinction of the sketch features. To this end, we have made efforts in three aspects. First, a novel multi-scale residual block is designed. Compared with the conventional basic residual block, it can better perceive multi-scale information and reduce the number of parameters during training. Second, a hierarchical residual structure is built by stacking multi-scale residual blocks in a specific way. In contrast with the single-level residual structure, the learned features from this structure are more sufficient. Last but not least, the compact triplet-center loss is proposed specifically for the sketch recognition task. It can solve the problem that the triplet-center loss does not fully consider too large intra-class space and too small inter-class space in sketch field. By studying the above modules, a hierarchical residual network as a whole is proposed for sketch recognition and evaluated on Tu-Berlin benchmark thoroughly. The experimental results show that the proposed network outperforms most of baseline methods and it is excellent among non-sequential models at present.

Sunyang Fu, David Chen, Huan He et al.

Background Concept extraction, a subdomain of natural language processing (NLP) with a focus on extracting concepts of interest, has been adopted to computationally extract clinical information from text for a wide range of applications ranging from clinical decision support to care quality improvement. Objectives In this literature review, we provide a methodology review of clinical concept extraction, aiming to catalog development processes, available methods and tools, and specific considerations when developing clinical concept extraction applications. Methods Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a literature search was conducted for retrieving EHR-based information extraction articles written in English and published from January 2009 through June 2019 from Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Scopus, Web of Science, and the ACM Digital Library. Results A total of 6,686 publications were retrieved. After title and abstract screening, 228 publications were selected. The methods used for developing clinical concept extraction applications were discussed in this review.