Biomedical Mathematics Group

A multi-agent reinforcement learning framework for exploring dominant strategies in iterated and evolutionary games - Fanpeng Song
2026-03-27 10:00 - 11:30 (Asia/Seoul) | B232 Seminar Room, IBS, 55 Expo-ro Yuseong-gu, Daejeon, Daejeon, 34126, Korea, Republic of
In this talk, we discuss the paper “A multi-agent reinforcement learning framework for exploring dominant strategies in iterated and evolutionary games” by Qi Su et al., Nat. Comm., 2026.
Abstract
Exploring dominant strategies in iterated games holds theoretical and practical significance across diverse domains. Previous studies, through mathematical analysis of limited cases, have unveiled classic strategies such as tit-for-tat, generous-tit-for-tat, win-stay-lose-shift, and zero-determinant strategies. While these strategies offer valuable insights into human decision-making, they represent only a small subset of possible strategies, constrained by limited mathematical and computational tools available to explore larger strategy spaces. To bridge this gap, we propose an approach using multi-agent reinforcement learning to delve into complex decision-making processes that go beyond human intuition. Our approach has led to the discovery of a strategy that we call memory-two bilateral reciprocity strategy. Memory-two bilateral reciprocity strategy consistently outperforms a wide range of strategies in pairwise interactions while achieving high payoffs. When introduced into an evolving population with diverse strategies, memory-two bilateral reciprocity strategy demonstrates dominance and fosters higher levels of cooperation and social welfare in both homogeneous and heterogeneous structures, as well as across various game types. This high performance is verified by simulations and mathematical analysis. Our work highlights the potential of multi-agent reinforcement learning in uncovering dominant strategies in iterated and evolutionary games.

Stochastics in medicine: Delaying menopause and missing drug doses - Sean Lawley
2026-04-03 11:00 - 12:00 | B232 Seminar Room, IBS, 55 Expo-ro Yuseong-gu, Daejeon, Daejeon, 34126, Korea, Republic of
Stochastic modeling and analysis can help answer pressing medical questions. In this talk, I will attempt to justify this claim by describing recent work on two problems in medicine. The first problem concerns ovarian tissue cryopreservation, which is a proven tool to preserve ovarian follicles prior to gonadotoxic treatments. Can this procedure be applied to healthy women to delay or eliminate menopause? How can it be optimized? The second problem concerns medication nonadherence. What should you do if you miss a dose of medication? How can physicians design dosing regimens that are robust to missed/late doses? I will describe (a) how stochastics theory offers insights into these questions and (b) the mathematical questions that emerge from this investigation.

Zoom : 997 8258 4700 (pw : [REDACTED]

A Data-Driven Computational Framework for Identifiability and Nonlinear Dynamics Discovery in Complex Systems - Wenrui Hao
2026-04-10 11:00 - 12:00 | B232 Seminar Room, IBS, 55 Expo-ro Yuseong-gu, Daejeon, Daejeon, 34126, Korea, Republic of
Data-driven modeling is essential for deciphering complex biological systems, yet its utility is often constrained by two fundamental hurdles: the inability to guarantee parameter identifiability and the high computational cost of learning nonlinear dynamics. This talk introduces a unified computational framework designed to overcome these challenges, bridging theoretical rigor with scalable machine learning.

The first component of the framework establishes a computational foundation for practical identifiability. By leveraging the Fisher Information Matrix and its theoretical links to coordinate identifiability, we propose an efficient method for identifiability assessment. We further introduce regularization-based strategies to manage non-identifiable parameters, thereby enhancing model reliability and facilitating robust uncertainty quantification.

To address the discovery of nonlinear dynamics, we present the Laplacian Eigenfunction-Based Neural Operator (LE-NO). This operator learning framework is specifically engineered for modeling reaction–diffusion equations. By projecting nonlinear operators onto Laplacian eigenfunctions, LE-NO achieves superior computational efficiency and generalization across varying boundary conditions, effectively bypassing the limitations of large-scale architectures and data scarcity.

Finally, we demonstrate the framework’s utility in the context of Alzheimer’s disease modeling. We show that this integrated approach ensures reliable parameter inference while capturing the intricate nonlinear dynamics of disease progression, providing a critical step toward the development of high-fidelity digital twins for neurodegenerative pathology.

Zoom : 997 8258 4700 (pw : [REDACTED]

Discovering network dynamics with neural symbolic regression - Olive Cawiding
2026-04-17 10:00 - 12:00 | B232 Seminar Room, IBS, 55 Expo-ro Yuseong-gu, Daejeon, Daejeon, 34126, Korea, Republic of
In this tallk, we discuss the paper “Discovering network dynamics with neural symbolic regression” by Zihan Yu et al., Nature Com. Science, 2026.
Abstract
Network dynamics are fundamental to analyzing the properties of high-dimensional complex systems and understanding their behavior. Despite the accumulation of observational data across many domains, mathematical models exist in only a few areas with clear underlying principles. Here we show that a neural symbolic regression approach can bridge this gap by automatically deriving formulas from data. Our method reduces searches on high-dimensional networks to equivalent one-dimensional systems and uses pretrained neural networks to guide accurate formula discovery. Applied to ten benchmark systems, it recovers the correct forms and parameters of underlying dynamics. In two empirical natural systems, it corrects existing models of gene regulation and microbial communities, reducing prediction error by 59.98% and 55.94%, respectively. In epidemic transmission across human mobility networks of various scales, it discovers dynamics that exhibit the same power-law distribution of node correlations across scales and reveal country-level differences in intervention effects. These results demonstrate that machine-driven discovery of network dynamics can enhance understandings of complex systems and advance the development of complexity science.

Foundation Models for Wearable Movement Data in Mental Health Research - Aqsa Awan
2026-04-24 10:00 - 12:00 | B232 Seminar Room, IBS, 55 Expo-ro Yuseong-gu, Daejeon, Daejeon, 34126, Korea, Republic of
In this tallk, we discuss the paper “Foundation Models for Wearable Movement Data in Mental Health Research” by Franklin Y. Ruan et al., arXiv, 2025.
Abstract
Pretrained foundation models and transformer architectures have driven the success of large language models (LLMs) and other modern AI breakthroughs. However, similar advancements in health data modeling remain limited due to the need for innovative adaptations. Wearable movement data offers a valuable avenue for exploration, as it’s a core feature in nearly all commercial smartwatches, well established in clinical and mental health research, and the sequential nature of the data shares similarities to language. We introduce the Pretrained Actigraphy Transformer (PAT), the first open source foundation model designed for time-series wearable movement data. Leveraging transformer-based architectures and novel techniques, such as patch embeddings, and pretraining on data from 29,307 participants in a national U.S. sample, PAT achieves state-of-the-art performance in several mental health prediction tasks. PAT is also lightweight and easily interpretable, making it a robust tool for mental health research.

Data-driven discovery of biological oscillator models - Lendert Gelens
2026-05-06 16:00 - 17:00 | B232 Seminar Room, IBS, 55 Expo-ro Yuseong-gu, Daejeon, Daejeon, 34126, Korea, Republic of
Oscillatory dynamics are a found everywhere in living systems, underlying processes such as metabolic regulation, cell division, and embryonic development. Identifying the mechanisms that generate these rhythms is challenging due to nonlinear interactions, multiple time scales, and limited access to all relevant variables. Data-driven approaches offer a promising route to infer dynamical models directly from time-series data. In this talk, I will discuss our work on data-driven discovery of models for (bio)chemical oscillators. In particular, I will present CLINE, a neural-network–based framework that infers key geometric features of phase space, such as nullclines, from oscillatory data and uses this information to construct low-dimensional dynamical models.

Zoom : 997 8258 4700 (pw : [REDACTED]

Impact of daylight saving time on physical activity patterns - Myna Lim
2026-05-08 10:00 - 12:00 | B232 Seminar Room, IBS, 55 Expo-ro Yuseong-gu, Daejeon, Daejeon, 34126, Korea, Republic of
In this talk, we discuss the paper “Impact of daylight saving time on physical activity patterns” by Hayoung Jeong et al., Nature Health, 2026.
Abstract
Daylight saving time (DST) remains contentious: some policymakers highlight behavioural benefits, while others emphasize health risks. Here we estimated the behavioural and physiological impacts of DST using longitudinal Fitbit measures from the National Institutes of Health All of Us Research Program. Avoiding strict modelling assumptions, we used a natural difference-in-differences design with Arizona (no DST) as a control against neighbouring Mountain Time states (observing DST). Contrary to common belief, DST transitions produced no net change in total daily steps. Instead, activity was reallocated to other times of day: fall transitions increased morning steps by 202 (confidence interval = [78, 326], P = 0.001) while reducing evening steps by 180 (confidence interval = [−263, −97], P < 0.001); spring transitions showed the opposite. Importantly, these treatment effects varied by demographics and across data-driven activity phenotypes (‘morning walker’, ‘neutral walker’ and ‘evening walker’). These disparities suggest that structural factors (for example, rigid work schedules, perceived safety) may constrain the capacity to flexibly adapt to time shifts for some populations. Physiologically, resting heart rate showed subtle intraday shifts mirroring behavioural changes, although differences were clinically insignificant. Our study provides a large-scale causal analysis of DST’s influence using continuous wearables data, illustrating how observational data can generate real-world evidence to inform health-relevant policies.

High-order Michaelis-Menten equations allow inference of hidden kinetic parameters in enzyme catalysis - Hyeong Jun Jang
2026-05-15 10:00 - 12:00 | B232 Seminar Room, IBS, 55 Expo-ro Yuseong-gu, Daejeon, Daejeon, 34126, Korea, Republic of
In this talk, we discuss the paper “High-order Michaelis-Menten equations allow inference of hidden kinetic parameters in enzyme catalysis” by Divya Singh et al., Nat. Comm., 2025.
Abstract
Single-molecule measurements provide a platform for investigating the dynamical properties of enzymatic reactions. To this end, the single-molecule Michaelis-Menten equation was instrumental as it asserts that the first moment of the enzymatic turnover time depends linearly on the reciprocal of the substrate concentration. This, in turn, provides robust and convenient means to determine the maximal turnover rate and the Michaelis-Menten constant. Yet, the information provided by these parameters is incomplete and does not allow access to key observables such as the lifetime of the enzyme-substrate complex, the rate of substrate-enzyme binding, and the probability of successful product formation. Here we show that these quantities and others can be inferred via a set of high-order Michaelis-Menten equations that we derive. These equations capture universal linear relations between the reciprocal of the substrate concentration and distinguished combinations of turnover time moments, essentially generalizing the Michaelis-Menten equation to moments of any order. We demonstrate how key observables such as the lifetime of the enzyme-substrate complex, the rate of substrate-enzyme binding, and the probability of successful product formation, can all be inferred using these high-order Michaelis-Menten equations. We test our inference procedure to show that it is robust, producing accurate results with only several thousand turnover events per substrate concentration.

Heejung Shim - Modelling spatial transcriptomics: from flexible cell-type deconvolution to multi-scale spatial factor analysis
2026-05-18 12:30 - 13:30 | B232 Seminar Room, IBS, 55 Expo-ro Yuseong-gu, Daejeon, Daejeon, 34126, Korea, Republic of
Abstract:
Spatial transcriptomics enables the study of gene expression within its spatial context, but introduces key statistical challenges, including mixed cellular composition and complex spatial structure. In this talk, I present two complementary modelling approaches.First, I introduce FlexiDeconv, a cell-type deconvolution method based on a modified Latent Dirichlet Allocation framework. A key feature of this method is its flexible use of reference information, allowing the model to balance prior information from scRNA-seq with signals from observed spatial data, and to adapt when the reference is incomplete or mismatched, a common challenge in practice.I then present WaviFM, a wavelet-based Bayesian sparse factor model that captures spatial gene expression patterns across multiple spatial scales, enabling the detection of both fine and broad spatial patterns. In addition, WaviFM can incorporate gene-set information to guide factor inference, while allowing for uncertainty and potential errors in these annotations.Together, these methods illustrate how flexible modelling of prior information and multi-scale modelling of spatial structure can improve our ability to extract biologically meaningful signals from spatial transcriptomics data.

Mathematics of diffusive signaling - Alan Lindsay
2026-05-22 11:00 - 12:00 | B232 Seminar Room, IBS, 55 Expo-ro Yuseong-gu, Daejeon, Daejeon, 34126, Korea, Republic of
Diffusive transport is one of the most fundamental mechanisms by which information, mass, and chemical signals propagate in physical and biological systems. In many settings—ranging from cellular signaling to chemical sensing—communication is mediated by particles undergoing random motion and interacting with small, spatially localized targets. This talk explores the mathematical structures underlying diffusive signaling, emphasizing how geometry, stochasticity, and multiscale effects shape signal detection and reliability. Using tools from stochastic processes, partial differential equations, and asymptotic analysis, I will describe how seemingly microscopic features can exert a dominant influence on macroscopic signaling outcomes, and highlight recent progress on quantifying signal strength, timing, and variability in complex geometries.

Zoom : 997 8258 4700 (pw : [REDACTED]

Causal Generalist Medical AI - Hongtu Zhu
2026-05-27 16:00 - 17:00 | ZOOM ID: 997 8258 4700 (Biomedical Mathematics Online Colloquium), (pw: [REDACTED]
The rapid evolution of flexible and reusable artificial intelligence (AI) models is transforming medical science. This short course introduces Causal Generalist Medical AI (Causal GMAI)—a paradigm that integrates causal inference with generalist AI models to enhance interpretability, robustness, and generalizability in medical decision-making. Causal GMAI employs self-supervised, semi-supervised, and supervised learning on diverse multimodal datasets—including imaging, electronic health records, clinical trials, laboratory results, genomics, knowledge graphs, and medical text—to perform a wide range of tasks with minimal task-specific supervision. By embedding causal reasoning, these models go beyond prediction to infer underlying causal relationships, improving diagnostic accuracy, treatment recommendations, and personalized medicine. The course covers key technical components such as causal discovery, counterfactual reasoning, and domain adaptation, alongside real-world applications. We will also explore challenges in regulation, validation, and dataset curation to ensure clinical reliability and ethical deployment. Designed for researchers, clinicians, data scientists, and AI practitioners, this course provides a foundation for advancing the next generation of trustworthy and interpretable medical AI.

Zoom : 997 8258 4700 (pw : [REDACTED]

Circadian rhythm profiles derived from accelerometer measures of the sleep-wake cycle in two cohort studies - Chitaranjan Mahapatra
2026-05-29 10:00 - 12:00 | B232 Seminar Room, IBS, 55 Expo-ro Yuseong-gu, Daejeon, Daejeon, 34126, Korea, Republic of
In this talk, we discuss the paper “Circadian rhythm profiles derived from accelerometer measures of the sleep-wake cycle in two cohort studies” by Sam vidil et al., Nature Communications, 2025.
Abstract:
Accelerometers allow objective measures of dimensions (rest-activity rhythm (RAR), daytime activity, sleep, and chronotype) of the bio-behavioural manifestation of circadian rhythm (CR) using multiple metrics in large-scale studies. These dimensions are rarely examined together due to methodological challenges of using correlated data. To address this challenge, we propose a two-step approach consisting of data reduction of CR metrics using principal component analyses, followed by k-means clustering to identify groups of individuals with a similar profile using data from the Whitehall II (N = 3,991, mean age=69.4years) and UK Biobank (N = 54,995, mean age=67.5years) cohort studies. Our analyses identified nine CR clusters: two presented extreme (most robust/poorest) RAR and (highest/lowest) daytime activity, two robust RAR with opposite sleep profiles (longer and efficient/shorter and fragmented), one high-intensity physical activity, and four poor RAR (one characterised by late chronotype, two by low activity but opposite sleep profiles, and one by restless (agitated) sleep). The participants in these nine clusters differed on sociodemographic, behavioural and health-related factors. Findings were similar in these two independent cohort studies, highlighting the validity of our approach. Most previous studies have used only the RAR dimension of circadian rhythm, and here we show that this might be an oversimplification as demonstrated by nine clusters characterised by combinations of RAR, daytime activity, sleep, and chronotype. Our innovative approach demonstrates feasibility of using all dimensions to study the impact of circadian rhythm dysregulation on health.

Bridging known and unknown dynamics by transformer-based machine-learning inference from sparse observations - Gyuyoung Hwang
2026-06-05 10:00 - 12:00 | B232 Seminar Room, IBS, 55 Expo-ro Yuseong-gu, Daejeon, Daejeon, 34126, Korea, Republic of
In this talk, we discuss the paper “Bridging known and unknown dynamics by transformer-based machine-learning inference from sparse observations” by Zheng-Meng Zhai et al., Nature Communications, 2025.
Abstract:
In applications, an anticipated issue is where the system of interest has never been encountered before and sparse observations can be made only once. Can the dynamics be faithfully reconstructed? We address this challenge by developing a hybrid transformer and reservoir-computing scheme. The transformer is trained without using data from the target system, but with essentially unlimited synthetic data from known chaotic systems. The trained transformer is then tested with the sparse data from the target system, and its output is further fed into a reservoir computer for predicting its long-term dynamics or the attractor. The proposed hybrid machine-learning framework is tested using various prototypical nonlinear systems, demonstrating that the dynamics can be faithfully reconstructed from reasonably sparse data. The framework provides a paradigm of reconstructing complex and nonlinear dynamics in the situation where training data do not exist and the observations are random and sparse.

Insulin resistance prediction from wearables and routine blood biomarkers - Dongju Lim
2026-06-12 10:00 - 12:00 | B232 Seminar Room, IBS, 55 Expo-ro Yuseong-gu, Daejeon, Daejeon, 34126, Korea, Republic of
In this talk, we discuss the paper “Insulin resistance prediction from wearables and routine blood biomarkers” by Ahmed A. Metwally et al., Nature, 2026.

Abstract:
Insulin resistance (IR), a primary precursor to type 2 diabetes, is characterized by impaired insulin action in tissues1. However, diagnostic methods remain expensive and inaccessible, which hinders early intervention2,3. Here we present the WEAR-ME study, a large, remotely conducted study of IR (n = 1,165 participants; median body mass index (BMI) = 28 kg m−2, median age = 45 years, median haemoglobin A1c (HbA1c) = 5.4%) that uses time-series data from wearable devices and routine blood biomarkers to train deep neural networks against a ground-truth measure of IR (homeostatic model assessment of IR; HOMA-IR). Using a HOMA-IR cut-off of 2.9, our multimodal model achieved robust performance (area under the receiver operating characteristic curve (AUROC) = 0.80, sensitivity = 76%, specificity = 84%) with data from wearable devices, together with demographic and routine blood biomarker data. To enhance the use of time-series data from wearables, we fine-tuned a wearable foundation model (WFM) pretrained on 40 million hours of sensor data. In an independent validation cohort (n = 72), a model integrating WFM-derived representations with demographic data surpassed a demographics-only baseline (AUROC = 0.75 versus 0.66). Moreover, adding WFM-derived representations to a model with demographics, fasting glucose and a lipid panel substantially improved performance, compared with an identical model without data from wearables (AUROC = 0.88 versus 0.76). We integrate IR prediction into a large language model to contextualize the results and facilitate personalized recommendations. This work establishes a scalable, accessible framework for the early detection of metabolic risk, which could enable timely lifestyle interventions to prevent progression to type 2 diabetes.
