biomedical data scientists

Abstract: In vision and scientific domains involving spatial data, a key question is whether node feature values vary independently across space or form coherent spatial structures. Classical spatial autocorrelation statistics such as Moran's $I$ and Geary's $C$ quantify this phenomenon but operate on a single scalar variable with fixed neighbourhood weights, limiting their use for high-dimensional graph-like data. We introduce SAIL (Spatial Autocorrelation Index Learner), a differentiable framework that generalises spatial autocorrelation into a learnable operator by jointly learning feature projections defining candidate scalar fields and inter-node neighbourhood affinities. SAIL produces interpretable local and global spatial coherence descriptors, enabling supervised prediction and unsupervised discovery of spatial autocorrelation modes and hotspots. We show that SAIL exactly recovers classical spatial statistics under appropriate parametrisations and, for tasks driven by latent spatial autocorrelation, can approximate the Bayes-optimal predictor with an inductive bias matched to such tasks. Experiments on synthetic data and large-scale biomedical graphs demonstrate statistical correctness and discovery of spatial coherence with applications across vision, geospatial analysis, and biomedicine. The code repository is available at: https://github.com/pkeller00/SAIL.

Abstract: Open-ended discovery requires learning from repeated attempts while continuing to explore directions whose value is not yet apparent. Search with a frozen large language model (LLM) can reuse previous solutions in context, but cannot update the model from its successes and failures on the test problem. Reinforcement learning (RL) enables such adaptation; however, strongly favoring high-reward trajectories may suppress low-reward yet potentially promising directions too early. We introduce CURIO, a curiosity-driven test-time learning framework that complements task feedback with an Intrinsic Curiosity World Model (ICWM). The ICWM learns transitions in the policy's hidden-state representation and supplies prediction-error bonuses at sampled tokens outside the policy's top-k choices. Epoch normalization and an annealed weight regulate their contribution to the policy update. On six mathematical discovery tasks and single-cell denoising with Qwen3 backbones from 8B to 235B, three-run means improve over a matched task-only RL control on five mathematical objectives, match the best reported performance on Circle Packing, and improve denoising Score and mean squared error (MSE) on both held-out corpora at every tested scale. Relative gains reach 18.3% on Hadamard and 10.8% on denoising Score. Code-diversity measurements show greater structural variation among generated programs, supporting curiosity as a complementary exploration signal for learning in open-ended discovery.

Abstract: The dynamics of cells, organisms, and fluids are often modeled as probability distributions evolving over time. Reconstructing and extrapolating this evolution from unpaired snapshots requires assumptions about the underlying process. Wasserstein gradient flows are a common choice, but they cannot describe conservative or periodic dynamics. Lagrangian mechanics in Wasserstein space covers both, but existing methods for learning it are simulation-based: they run a numerical solver at every training step, which makes training expensive. We propose Double-Stitch, a simulation-free method that learns these mechanics by penalizing the residual of the equation of motion along a learned population path. We derive this equation from a Clebsch variational principle that does not require gradient velocities, and show that the residual vanishes exactly when the equation holds. We test Double-Stitch on synthetic, single-cell and ocean vortex datasets and find that it matches or outperforms gradient-flow methods and simulation-based WLM on most tasks, while training $4$-$14$ times faster than WLM. We provide a JAX implementation of Double-Stitch at https://github.com/BasisResearch/stitching.

Abstract: Many physiological time series, such as cardiac and brain recordings, exhibit cyclostationarity: their statistics vary periodically with an underlying cycle phase. Corruption from motion, poor contact, and physiological interference obscures morphology needed for diagnosis, making signal restoration essential. Existing diffusion approaches condition on corrupted observations alone and must learn cyclic structure implicitly. We instead propose two inductive biases which encode cyclostationarity: a shift-covariant wavelet representation and dense per-sample phase conditioning inferred from the corrupted input. We further introduce a training-free cyclostationarity index that quantifies phase structure and predicts when phase conditioning will help. Finally, we propose antithetic coupling of reverse trajectories to reduce sampling variance while achieving comparable performance with fivefold fewer network evaluations. Across modalities, our results show that explicitly encoding measurable cyclic structure improves physiological time-series restoration.

Abstract: Pre-training Graph Neural Networks (GNNs) via self-supervised learning has become a dominant paradigm, yet efficiently adapting frozen encoders remains a challenge. Graph prompting offers a parameter-efficient alternative to fine-tuning, but existing methods largely treat pre-trained models as opaque feature extractors, ignoring their internal spectral structure. In this work, we identify a systematic phenomenon in pre-trained GNNs, which we term spectral bias: optimization during pre-training disproportionately aligns representations with directions associated with large singular values, leaving low-energy directions under-explored. We show that these underutilized directions can encode complementary information that is beneficial for downstream adaptation, especially under distribution shift. To leverage this insight, we propose Spectral Reverse Prompt (SRP), a prompting framework that rebalances the spectral contributions of frozen GNN encoders. SRP applies a learnable soft-thresholding mask in the spectral domain to down-weight dominant directions while amplifying weaker ones. In addition, SRP incorporates a null-space augmentation module that captures variation in directions with minimal activation under the frozen encoder. Extensive experiments across multiple benchmarks demonstrate that SRP achieves state-of-the-art performance with minimal additional parameters, highlighting that reweighting spectral components is a principled and effective strategy for parameter-efficient graph adaptation.

Abstract: Agentic biomedical machine learning (ML) draws on complementary advances in biomedical evidence acquisition and executable program search. Existing systems connect aspects of these capabilities, but coordinating them throughout program search remains challenging. New evidence must guide candidate construction, execution outcomes must inform subsequent discovery and reuse, and validation demands must fit the search budget. We introduce BioDyad, which couples biomedical discovery and ML engineering through two hierarchies within Monte Carlo graph search. Its scientific hierarchy combines prior biomedical guidance with iterative discovery, then links biomedical plans to execution outcomes in memory for reuse across candidates. Its engineering hierarchy moves candidate programs from smoke execution, through train/validation evaluation, to full-data retraining. We evaluate BioDyad on the 76-task BioXArena benchmark under a two-hour per-task budget with three matched LLM backends. It achieves the highest penalized all-task score and task success rate among four agent methods and a one-shot baseline under each backend. These results support coordinating biomedical discovery and ML engineering to integrate external knowledge into executable programs across heterogeneous biomedical tasks.

Abstract: Artificial neural networks (ANNs) usually represent neural transmission with fixed trainable weights during a training batch, which omits short-term changes in synaptic efficacy. In addition, the discrete time-step simulation requires additional temporal processing that many conventional ANN architectures do not use. To overcome these challenges, we propose Purin, a biology-inspired and ANN-compatible mechanism, that introduces synaptic efficacy modulation into conventional convolutional neural networks. Purin uses a time-interval-based abstraction for neural activities, which allows Purin to introduce short- and long-term synaptic efficacy changes without using discrete time-steps. Purin introduces a bounded factor to represent temporary synaptic efficacy changes, together with two weight matrices that represent input-side and output-side efficacy. The weight matrices are updated by backpropagation and interpreted as the long-term synaptic efficacy changes. Experimental results show that after removing the confounding factors in the AlexNet, VGG11, and GoogLeNet architectures, Purin improves the classification accuracies in all three models across the evaluated datasets.

Abstract: Scientific measurements such as single-cell RNA (scRNA) sequencing often take the form of nonnegative integer counts, whereas continuous-state diffusion models approximate this discrete structure using continuous coordinates. Building on stochastic chemical reaction networks (CRNs), a class of count-native Markov jump processes, we introduce CRNDiff, a structured framework that combines count-space diffusion with inference-time conditioning on rare subpopulations. An independent birth--death instantiation yields a closed-form transition kernel for forward noising. This kernel enables reverse sampling via forward-filtering backward-sampling (FFBS) and supports data-driven selection of the terminal noising time, eliminating the need for a validation sweep. This tractability also lets us introduce tilted Feynman--Kac (FK) steering, a method for sampling target subpopulations from a frozen generator without retraining. By tilting posterior marginals before FK particle correction, steering mitigates importance-weight concentration when the target population is rare. Using scRNA-seq data from the human heart cell atlas, we test the ability of CRNDiff to generate cell-type-specific distributions. Across the three evaluated target populations, CRNDiff achieves the highest conditional fidelity among the evaluated generative models, with larger mean purity margins for rarer target populations. Generated cells preserve marker-level differential-expression structure. Replacing real training cells for the target classes with generated cells yields downstream classification performance approaching that of the real-data reference.

Abstract: Leave-One-Subject-Out (LOSO) evaluation estimates generalisation performance for subject-based classification but makes Neural Architecture Search (NAS) computationally expensive because a fully nested implementation requires N independent architecture searches and, assuming approximately linear training cost, scales as O(N^2). We propose a leakage-free, block-based approach that shares NAS runs across subjects. On the BioVid Heat Pain dataset, our approach increased the mean accuracy from 82.79% to 83.39% while reducing the number of parameters by up to 99.2%.