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Mihaela van der Schaar

Publications and source records attributed to Mihaela van der Schaar.

At least 19 recordsLinked to original sources
arXiv2026

APOD: reasoning-guided agentic population ordinary differential equation discovery for pharmacological digital twins

Establishing ordinary differential equations (ODEs) describing population data is a fundamental part of mathematical modeling in pharmacology, crucial to developing digital twins. However, doing so from sparse, noisy data is a slow, expert-driven task. Existing automated methods either search a restricted model space or ignore population inter-individual variability. Here we introduce APOD (Agentic Population ODE Discovery), a language-model agent that iteratively reasons over biological knowledge and fit diagnostics in an open-ended search space to discover a population digital twin (PDT), i.e., a shared ODE system with between-subject variability. On synthetic pharmacokinetic and tumor-dynamics benchmarks, APOD recovered ground-truth structures in 94-100\% of runs, 12-fold faster in median than an established library-based search. On real cohorts it converged to valid structures, and proposed a PDT of radioligand-therapy-induced platelet dynamics that predicts thrombocytopenia from first-cycle data and simulates alternative dosing schedules that lower the predicted risk of toxicity.

q-bio.QM↗
arXiv2026

TimeTok: Granularity-Controllable Time-Series Generation via Hierarchical Tokenization

Time-series data are inherently multiscale, spanning diverse temporal granularities from coarse trends to fine-scale dynamics. However, existing time-series generative models provide limited control over the temporal granularity of both inputs and outputs, restricting their ability to condition on user-provided coarse sketches and generate samples at a desired target granularity. To address this, we introduce TimeTok, a unified framework for Granularity-Controllable Time-Series Generation (GC-TSG), which generates time series at any target granularity from any coarser input (e.g., rough sketches) or without conditioning. At the core of TimeTok is a hierarchical tokenization strategy that maps time series into an ordered sequence of tokens, from coarse to fine temporal granularity. Our autoregressive generation process operates across these granularity levels, producing token blocks that are decoded back into continuous time series. This design naturally enables GC-TSG within a single framework, where controlling the number of token blocks provides explicit control over output detail. Experiments show that TimeTok excels at GC-TSG tasks while achieving state-of-the-art performance in standard generation. Furthermore, we showcase TimeTok's potential as a foundational tokenizer by training on multiple datasets with heterogeneous temporal granularities, verifying strong transferability that consistently outperforms models trained on individual datasets. To our knowledge, this is the first unified framework that covers the full generative spectrum for time series, offering a valuable foundation for models that benefit from diverse temporal granularities.

cs.AI↗
arXiv2026

Recursive Scaling in Masked Diffusion Models

Masked diffusion models (MDMs) generate sequences by iteratively refining a partially masked state and committing tokens in parallel. We introduce recursion in MDMs and propose new Recursive Masked Diffusion Models (R-MDMs), which apply a shared denoising transformer $L$ times within each denoising step, adding recursive depth as an additional compute axis without increasing parameter count. Across structured generation tasks, recursive depth improves quality at fixed parameter budget, matches substantially larger non-recursive models at matched FLOPs, and can reduce the number of denoising steps needed to reach a target quality. We interpret these gains with a dependence--fidelity decomposition of parallel decoding error: recursion refines model marginals at a fixed masked state, whereas denoising steps change that state by committing tokens. Building on this analysis, we propose to treat decoding as a two-axis decision (how many loops to run and which tokens to commit) and show that entropy-guided adaptive rules improve the quality--compute frontier over fixed schedules, transferring across various tasks on Sudoku, Countdown, RNA, and executable math generation. Together, these results establish recursive depth as a practical, complementary test-time scaling mechanism for MDMs.

cs.LG↗
arXiv2026

On-Policy or Off-Policy Learning? A Systematic Study of Distillation Dynamics

On-policy learning has been argued to reduce catastrophic forgetting, produce sparser parameter updates, and improve generalisation. However, existing comparisons between supervised fine-tuning and reinforcement learning vary many factors simultaneously, making the contribution of rollout policy difficult to isolate. We study the effect of rollout policy in a controlled strong-to-weak distillation setting, by independently varying rollout policy, token-level KL direction, and learning rate across the Llama3 and Qwen2.5 model families and reasoning tasks spanning scientific, medical, and arithmetic domains. Our analysis reveals a nuanced picture of distillation dynamics in which rollout policy does not necessarily play a central role. Instead, token-level KL direction more clearly shapes task performance and output coverage, while learning rate governs forgetting and update sparsity. Analysis of KL gradients and experiments along a continuous student-teacher rollout-policy spectrum explain this pattern: forward KL is remarkably robust to rollout policy, with its performance stable and strong despite changes to the rollout policy, whereas reverse KL is substantially more sensitive and favours student-generated rollouts. On-policy data nevertheless improves generalisation to harder variants of the Countdown arithmetic task under both KL directions, although this advantage does not reliably persist after subsequent RLVR. Our broader conclusions remain robust to removing gradient clipping, using sampled KL estimators, and training on tasks requiring longer reasoning chains. Overall, our results challenge the view that on-policy rollouts are inherently preferable and show that their value depends critically on the objective, evaluation setting, and optimisation hyperparameters.

cs.LG↗
arXiv2026

Learning Continuous Patient Trajectories from Electronic Health Records

Electronic health records provide irregular observations of latent patient states that evolve continuously over time. Recent autoregressive models condition on clinical histories to forecast future events as sequences of discrete observations. Conversely, multi-marginal flow matching provides a continuous-time formulation, but using multiple observations to supervise training paths does not itself give the learned dynamics access to preceding patient history. We introduce EHRFlow, a multi-marginal flow-matching framework that conditions on encoded patient history, thereby allowing future dynamics to depend on the patient's prior clinical trajectory. Our proposed framework accommodates irregular observation times and supports forecasting at arbitrary horizons. Across controlled synthetic benchmarks, EHRFlow improves clinical-code forecasting and latent-state recovery. On real-world clinical datasets comprising more than one million patients, including an independent external validation cohort, EHRFlow improves horizon-averaged top-5 clinical-code accuracy over autoregressive and history-independent flow-matching baselines. Finally, in a controlled counterfactual simulation, conditional guidance approximates the known effect of an antihypertensive intervention without training a task-specific outcome model.

cs.LG↗
arXiv2026

SeqMaestro: From nucleotide sequences to biological hypotheses through interpretable machine learning

Nucleotide sequence analysis is central to problems spanning regulatory genomics, evolutionary biology, and phenotype prediction. Classical bioinformatics methods extract interpretable sequence properties such as motifs and k-mer composition, but their flexibility is limited. In contrast, modern deep learning models can learn powerful predictive representations directly from raw sequences, yet their internal representations and decision mechanisms are difficult to inspect. Interpretable machine learning methods (e.g., sparse linear models and decision trees) provide human-understandable representations of predictive relationships but are not designed to operate directly on nucleotide sequences. Here, we introduce SeqMaestro, a machine learning framework that proposes biological hypotheses from nucleotide sequences using interpretable models. Our solution is centered around a two-layer interface that connects nucleotide sequences with the broader ecosystem of interpretable machine learning. SeqMaestro uses this interface to fit diverse combinations of interpretable models, feature representations, and extraction strategies, leveraging variability across transparent models to identify robust biological signals and richer predictive relationships than feature importance alone can provide. The system also supports data transformation and cleaning, model fitting, hyperparameter tuning, reliability analysis, and synthesis of results into a contextualized written report. By providing these capabilities through a no-code workflow, SeqMaestro is designed to make interpretable sequence analysis accessible to researchers without requiring extensive programming or machine learning expertise. SeqMaestro thereby provides an accessible route from nucleotide sequences to biological hypotheses.

cs.LG↗
arXiv2026

Timely Clinical Diagnosis through Active Test Selection

There is growing interest in using machine learning (ML) to support clinical diagnosis, but most approaches rely on static, fully observed datasets and fail to reflect the sequential, resource-aware reasoning clinicians use in practice. Diagnosis remains complex and error prone, especially in high-pressure or resource-limited settings, underscoring the need for frameworks that help clinicians make timely and cost-effective decisions. We propose ACTMED (Adaptive Clinical Test selection via Model-based Experimental Design), a diagnostic framework that integrates Bayesian Experimental Design (BED) with large language models (LLMs) to better emulate real-world diagnostic reasoning. At each step, ACTMED selects the test expected to yield the greatest reduction in diagnostic uncertainty for a given patient. LLMs act as flexible simulators, generating plausible patient state distributions and supporting belief updates without requiring structured, task-specific training data. Clinicians can remain in the loop; reviewing test suggestions, interpreting intermediate outputs, and applying clinical judgment throughout. We evaluate ACTMED on real-world datasets and show it can optimize test selection to improve diagnostic accuracy, interpretability, and resource use. This represents a step toward transparent, adaptive, and clinician-aligned diagnostic systems that generalize across settings with reduced reliance on domain-specific data.

cs.AI↗
arXiv2026

Skill Neologisms: Towards Skill-based Continual Learning

Modern LLMs show mastery over an ever-growing range of skills, as well as the ability to compose them flexibly. However, extending model capabilities to new skills in a scalable manner is an open problem: fine-tuning and parameter-efficient variants risk catastrophic forgetting, while context-based approaches have limited expressiveness and are constrained by the model's effective context. We explore skill neologisms--soft tokens integrated in the model's vocabulary and optimized to improve capabilities over a specific skill--as a way to selectively acquire new skills without weight updates. We first observe that pretrained LLMs already exhibit tokens associated with procedural knowledge. We then show on a controlled synthetic task that skill neologisms can be learned to improve model capabilities on specific skills while being composable with out-of-distribution skills, and that independently trained skill neologisms can be composed zero-shot. Finally, we validate zero-shot composition of independently learned skill neologisms on the more realistic natural language setting of the Skill-Mix benchmark. These results suggest that skill neologisms may provide a scalable path towards skill-based continual learning.

cs.LG↗
arXiv2026

Automatic Construction of Clinical Scoring Systems with LLM Agents

Modern clinical practice relies on evidence-based guidelines implemented as compact scoring systems composed of a small number of interpretable decision rules. While machine-learning models achieve strong performance, many fail to translate into routine clinical use due to misalignment with workflow constraints such as memorability, auditability, and bedside execution. We argue that this gap arises not from insufficient predictive power, but from optimizing over model classes that are incompatible with guideline deployment. Deployable guidelines often take the form of unit-weighted clinical checklists, formed by thresholding the sum of binary rules, but learning such scores requires searching an exponentially large discrete space of possible rule sets. We introduce AgentScore, which performs semantically guided optimization in this space by using LLMs to propose candidate rules and a deterministic, data-grounded verification-and-selection loop to enforce statistical validity and deployability constraints. Across eight clinical prediction tasks, AgentScore outperforms existing score-generation methods and achieves AUROC comparable to more flexible interpretable models despite operating under stronger structural constraints. On two additional externally validated tasks, AgentScore achieves higher discrimination than established guideline-based scores.

cs.LG↗
arXiv2026

Knowledge-Informed Kernel State Reconstruction from Heterogeneous Partial Observations

Real-world scientific systems are rarely observed through complete, regularly sampled state trajectories. Instead, measurements are often partial, noisy, and heterogeneous, providing fragmented views of latent dynamical states. We introduce MAAT (Model Aware Approximation of Trajectories), a framework for knowledge-informed Kernel State Reconstruction in partially observed dynamical systems. MAAT formulates reconstruction in a reproducing kernel Hilbert space and incorporates heterogeneous observation operators together with semantic and structural priors, including non-negativity, conservation constraints, and domain-specific measurement models. This yields smooth, physically consistent state estimates with analytic time derivatives, providing a principled interface between fragmented measurements and downstream mechanistic discovery methods such as symbolic regression. Across nine scientific benchmarks, multiple noise regimes, and a real-world COVID-19 dataset, MAAT substantially reduces trajectory and derivative reconstruction error relative to strong baselines.

cs.LG↗
arXiv2026

When AI Agents Compete for Jobs: Strategic Capabilities and Economic Dynamics of AI Labour Markets

Emerging agentic marketplaces provide the economic infrastructure for matching and coordinating the large amounts of AI agents used in agentic swarms. Unlike human workers, AI agents can operate on multiple jobs simultaneously, acquire skills rapidly, and labor without wage floors. These differences introduce a new segment of $\textbf{AI labor markets}$, where AI agents interact with each other at a much higher frequency than human markets. Yet we lack frameworks to understand how such markets behave in light of economic forces that shape labor markets, such as adverse selection and reputation dynamics. To explore this, we introduce $\texttt{AI-Work}$, a tractable, simulated gig economy where Large Language Model (LLM) agents compete for jobs, develop skills, and adapt their strategies under uncertainty and competitive pressure. Our experiments examine three domains of capabilities that successful agents possess: $\textbf{metacognition}$ (accurate self-assessment of skills), $\textbf{competitive awareness}$ (modeling rivals and market dynamics), and $\textbf{long-horizon strategic planning}$. Agents with these capabilities consistently achieve higher profits, market share, and stronger adaptation than competing agents. Through $\texttt{AI-Work}$, we hope to provide a foundation to explore the microeconomic properties of AI-only labor markets, and a conceptual framework to study the strategic reasoning capabilities of participating AI agents.

cs.MA↗
arXiv2026

OncoSynth: Synthetic data generation for treatment effect estimation in oncology

In oncology, access to patient-level data is often restricted. Synthetic data provides an alternative for analyzing treatment effectiveness, but existing methods for synthetic data generation fail to preserve the causal relationships between covariates, treatments, and outcomes, thereby leading to biased estimates of treatment effects. Here, we introduce OncoSynth, a generative, causally-aware machine learning framework designed to produce synthetic cohorts that enable accurate estimation of population- and patient-level treatment effects. OncoSynth uses a diffusion-based sequential approach to model how covariates influence treatment assignment and how treatment affects survival. We evaluate OncoSynth using large lung (N = 37,128) and breast cancer (N = 17,046) cohorts. Our results show that OncoSynth generates high-fidelity synthetic patient cohorts that preserve real-world patient, treatment, and outcome distributions. Notably, OncoSynth improves treatment effect estimation over existing approaches, by reducing population-level treatment effect error by up to 66%, and patient-level treatment effect error by up to 58%. Thereby, OncoSynth supports reliable evidence generation for precision oncology in settings where data sharing is restricted.

cs.LG↗
arXiv2026

$\text{DT}^2$: Decision-Targeted Digital Twins

A digital twin (DT) is a virtual model of a real-world system that can assist decision-making by simulating scenarios induced by different policies. However, typical machine learning-based DTs do not optimise for this use case. We prove that, when model capacity is limited, training DTs to minimise one-step transition errors can produce suboptimal models for ranking sets of policies according to a reward function. We further show that this holds empirically, even with expressive model classes. To address this, we introduce $\text{DT}^2$, a decision-targeted DT training paradigm. Firstly, $\text{DT}^2$ uses fitted Q-evaluation to estimate values of candidate policies from offline data. A DT is then trained to generate rollouts that preserve pairwise policy rankings derived from these proxy ground-truth values with an architecture-agnostic loss function. We empirically demonstrate the efficacy of our method across a range of settings and architectures. $\text{DT}^2$ consistently improves policy ranking and reduces decision regret during policy selection relative to conventional DT training, both for policies used during training and for unseen policies, while maintaining a good level of raw simulation fidelity.

cs.LG↗
arXiv2026

Position: The ML Community Must Build an AI-Augmented Peer-Review Ecosystem

Peer review, the bedrock of scientific advancement in machine learning (ML), is strained by a crisis of scale. Exponential growth in manuscript submissions to premier ML venues such as NeurIPS, ICML, and ICLR is outpacing the finite capacity of qualified reviewers, leading to concerns about review quality, consistency, and reviewer fatigue. This position paper argues that AI-assisted peer review must become an urgent research and infrastructure priority. We advocate for a comprehensive AI-augmented ecosystem, leveraging Large Language Models (LLMs) not as replacements for human judgment, but as sophisticated collaborators for authors, reviewers, and Area Chairs (ACs). We propose specific roles for AI in enhancing factual verification, guiding reviewer performance, assisting authors in quality improvement, and supporting ACs in decision-making. Crucially, we contend that the development of such systems hinges on access to more granular, structured, and ethically-sourced peer review process data. We outline a research agenda, including illustrative experiments, to develop and validate these AI assistants, and discuss significant technical and ethical challenges. We call upon the ML community to proactively build this AI-assisted future, ensuring the continued integrity and scalability of scientific validation, while maintaining high standards of peer review.

cs.AI↗
arXiv2026

Fact-Augmented Lookahead Planning for LLM Agents

Large Language Models (LLMs) are increasingly capable, but LLM agents still struggle to plan effectively in interactive, partially observable, long-horizon environments when search is unguided or recent history is insufficient. We introduce LWM-Planner, a fact-augmented lookahead planning framework that improves agent behavior purely through in-context learning. After each episode, the agent extracts task-critical atomic facts from its trajectories, validates candidates with a lightweight predictive-consistency filter (and optionally compresses them), and uses the resulting fact set to condition action proposal, single-step latent world-model simulation, and state-value estimation. Planning then proceeds via recursive, depth-limited lookahead over candidate trajectories conditioned on the accumulated facts and recent history, enabling online improvement without parameter updates. We provide abstraction-style motivation: treating facts as reducing state aliasing (proxy $ε_{\mathrm{sim}}$) and fact-conditioned simulation as lowering one-step error (proxy $δ_{\mathrm{model}}$), without claiming formal guarantees. Empirically, on text FrozenLake variants, CrafterMini, and ALFWorld, the approach improves cumulative return over ReAct/Reflexion and search-only baselines, suggesting that additional test-time search is most useful when grounded by compact, experience-derived facts.

cs.LG↗
arXiv2026

Nonparametric LLM Evaluation from Preference Data

Evaluating the performance of large language models (LLMs) from human preference data is crucial for obtaining LLM leaderboards. However, many existing approaches either rely on restrictive parametric assumptions or lack valid uncertainty quantification when flexible machine learning methods are used. In this paper, we propose a nonparametric statistical framework, called DMLRank, for comparing and ranking LLMs from preference data using debiased machine learning (DML). For this, we introduce generalized average ranking scores (GARS), which generalize commonly used ranking models, including the Bradley-Terry model or PageRank/ Rank centrality, with complex human responses such as ties. DMLRank comes with the following advantages: (i)~It produces statistically efficient estimates of GARS ranking scores. (ii) It naturally allows the incorporation of black-box machine learning methods for estimation. (iii) It can be combined with pre-trained LLM evaluators (e.g., using LLM-as-a-judge). (iv) It suggests optimal policies for collecting preference data under budget constraints. We demonstrate these advantages both theoretically and empirically using both synthetic and real-world preference datasets. In summary, our framework provides practitioners with powerful, state-of-the-art methods for comparing or ranking LLMs for leaderboards.

cs.LG↗
arXiv2026

Step-by-Step Optimization-like Reasoning in LLMs over Expanding Search Spaces

Verifiable reward training has improved mathematical and coding reasoning, but these domains capture only part of step-by-step decision making. Many real-world tasks require finding a high-value feasible plan among many valid alternatives. We introduce OPT*, a scalable family of optimization-style tasks for training and evaluating LLM step-by-step optimization-like reasoning along a complexity axis: each task provides a feasibility checker and evaluator, while a complexity parameter expands the search space without requiring new human labels. This motivates studying these tasks in two regimes: (i) solver-guided online policy optimization, which uses a solver as a value oracle for partial states and applies rank-based reward shaping to reinforce better next steps, and (ii) search-based offline RL when such solvers are unavailable. Theoretically, we relate success in large search spaces to the information a reasoner extracts per unit of search budget. Empirically, we ablate the ingredients that make search efficient on OPT* and show that training on OPT* improves step-by-step optimization-like reasoning.

cs.AI↗
arXiv2026

Active Timepoint Selection for Learning Measure-Valued Trajectories

Inferring continuous probability paths from sparse snapshots is a fundamental challenge in domains like single-cell biology, where high-fidelity data acquisition is often destructive and constrained by prohibitive sequencing costs. This motivates the need for active learning strategies to strategically select optimal measurement times. However, designing active learning policies for this setting remains an open problem: the target objects reside on the infinite dimensional Wasserstein space where standard Euclidean metrics are ill-defined, and current interpolation methods lack epistemic uncertainty quantification. We introduce a framework which extends active experimentation to the space of measures. By leveraging Linearized Optimal Transport (LOT), we map distributional snapshots into a tangent space amenable to Gaussian Process modeling, allowing us to construct a tractable probabilistic surrogate for the underlying probability path. This yields an acquisition policy that iteratively selects measurement times to minimize uncertainty. Empirical results demonstrate that our strategy outperforms uncertainty-agnostic baselines on both synthetic and real-world datasets.

cs.LG↗