arXiv subjects

Alexander Tong

Publications and source records attributed to Alexander Tong.

At least 19 recordsLinked to original sources

arXiv2026

Autoregressive Boltzmann Generators

Efficient sampling of molecular systems at thermodynamic equilibrium is a hallmark challenge in statistical physics. This challenge has driven the development of Boltzmann Generators (BGs), which allow rapid generation of uncorrelated equilibrium samples by combining a generative model with exact likelihoods and an importance sampling correction. However, modern BGs predominantly rely on normalizing flows (NFs), which either suffer from limited expressivity due to strict invertibility constraints (discrete time) or computationally expensive likelihoods (continuous time). In this paper, we propose Autoregressive Boltzmann Generators (ArBG) -- a novel autoregressive modelling framework -- that overcomes these limitations by departing from the flow-based BG paradigm. ArBG circumvents the topological constraints of flows and enables sequential inference-time interventions, while offering enhanced scalability by leveraging architectures effective in Large Language Models. We empirically demonstrate that ArBG leads to significant improvements over flow-based models across all benchmarks, but particularly in larger peptide systems such as the 10-residue Chignolin. Furthermore, we introduce Robin, a 132 million parameter transferable model trained with the ArBG framework which improves over the previous state-of-the-art, reducing the zero-shot energy error, E-W$_2$, on 8-residue systems by over 60$\%$. The code can be found at the following link: https://github.com/danyalrehman/autobg.

cs.LG↗

arXiv2026

Topological Flow Matching

Flow matching is a powerful generative modeling framework, valued for its simplicity and strong empirical performance. However, its standard formulation treats signals on structured spaces, such as fMRI data on brain graphs, as points in Euclidean space, overlooking the rich topological features of their domains. To address this, we introduce topological flow matching, a topology-aware generalization of flow matching. We interpret flow matching as a framework for solving a degenerate Schr\"odinger bridge problem and inject topological information by augmenting the reference process with a Laplacian-derived drift. This principled modification captures the structure of the underlying domain while preserving the desirable properties of flow matching: a stable, simulation-free objective and deterministic sample paths. As a result, our framework serves as a drop-in replacement for standard flow matching. We demonstrate its effectiveness on diverse structured datasets, including brain fMRIs, ocean currents, seismic events, and traffic flows.

cs.LG↗

arXiv2026

Hacking Generative Perplexity: Why Unconditional Text Evaluation Needs Distributional Metrics

Diffusion and continuous flow-based language models have emerged as the leading non-autoregressive alternatives to language modeling. Progress in both paradigms is overwhelmingly tracked by generative perplexity (gen-PPL): the per-token negative log-likelihood of samples under a frozen autoregressive (AR) scorer such as gpt2-large, typically paired with an empirical-entropy guardrail to rule out low-entropy collapse. We argue that this metric is unsound. By construction, gen-PPL measures only predictability under the scoring AR, not grammaticality or semantic coherence -- and the set of predictable but still low-quality sequences is combinatorially large. To make this concrete, we construct a suite of zero-parameter, deliberately naive samplers that achieve state-of-the-art gen-PPL on LM1B and OpenWebText at non-degenerate entropy, surpassing recently published diffusion and continuous-flow models while producing text that is incoherent by construction. We recommend evaluation suites that directly quantify the distributional divergence between generated and reference text, and use such a suite to re-benchmark recent non-autoregressive models, recovering a more faithful picture of the current state of the art.

cs.CL↗

arXiv2026

Why Are DMD Students Lazy? Understanding the Copying Behavior in Few-Step Distillation

Distribution Matching Distillation (DMD) compresses pretrained diffusion models into efficient few-step generators by aligning their noised distributions across all scales. In principle, such distribution-level supervision remains agnostic to specific noise-data pairings of the teacher; this provides the student the freedom to remap latent noise, a behavior consistently observed in low-dimensional settings. Surprisingly, we find that in high-dimensional settings, distilled students spontaneously reproduce the original noise-data pairings of the teacher, a phenomenon we term copying. We demonstrate that copying is neither a byproduct of adversarial objectives nor a result of teacher memorization. Instead, our evidence suggests that copying is an emergent property arising from the limited geometric freedom of the student model during high-dimensional distillation.

cs.LG↗

arXiv2026

Strong Stochastic Flow Maps

Flow and diffusion models generate high-quality samples in many modalities; however, many network evaluations are required during inference due to numerical integration of an underlying differential equation. Flow maps alleviate this problem by learning the solution map of the differential equation directly, enabling few-step sampling. Yet, current methods are restricted to approximating the solution map of ODEs. These methods can be used to learn the transition kernel of an SDE, thereby obtaining a solution map that recovers the marginal distributions of the process (weak convergence) rather than the solution path (strong convergence). We propose Strong Stochastic Flow Maps (SSFMs) as a novel framework for learning the strong solution map of additive-noise SDEs, directly generalizing deterministic flow maps to the stochastic setting. Further, a polynomial approximation to Brownian motion is introduced and shown to converge pathwise. These results enable a simulation-free training objective for the solution map of diffusion models. We demonstrate that SSFMs outperform previous stochastic flow map methods on image generation and enable few-step sampling of molecular systems.

cs.LG↗

arXiv2026

Entropy Across the Bridge: Conditional-Marginal Discretization for Flow and Schr\"odinger Samplers

For a fixed flow-based generative model under a small inference budget, sample quality can depend strongly on where the sampler spends its few function evaluations. Flow matching and Schr\"odinger bridges define probability paths, yet their inference grids are usually heuristic or inherited from one-endpoint diffusion. We derive a conditional-marginal entropy-rate objective for bridge-aware discretization, separating endpoint-conditioned bridge geometry from marginal flow evolution, and use it to build a training-free entropic inference-time scheduler from first principles. For Gaussian Brownian bridges this rate is closed-form and U-shaped, motivating boundary-heavy nonuniform grids. On trained two-dimensional bridge/flow models, the estimated profile recovers the predicted shape and improves 10-step ODE-Heun MMD over linear by 18.1%, with a paired 22.7% SDE-Heun improvement in the same low-NFE sweep. On EDM/CIFAR-10, the entropic time-discretization gives the best tested five-step FID (186.3 \pm 4.0 versus 200.5 \pm 2.9 for linear and 238.0 \pm 5.3 for cosine). On AlphaFlow protein generation, entropic conditional-marginal (cond-marg) scheduling shows advantage in low-NFE regimes on both CAMEO22 and ATLAS benchmarks. These results support entropy-rate scheduling as a practical low-budget allocation signal for high-dimensional bridge and flow samplers.

cs.LG↗

arXiv2026

Coupling Models for One-Step Discrete Generation

Generative modeling over discrete structures underpins applications across deep learning, from biological sequence design and code generation to large language models, yet generation often remains sequential, relying on autoregressive decoding or iterative refinement. In this work, we introduce Coupling Models(Coupling Models), a one-step discrete generative model that learns a direct coupling between discrete sequences and Gaussian latents. Unlike recent distillation methods that compress a pretrained multi-step sampler into a few steps, Coupling Model trains a purpose-built decoder to invert this coupling and generate samples in a single step. The model also avoids complex continuous flows over the simplex and hand-specified data-to-noise couplings. Empirically,Coupling Model improves the strongest one-step baselines in each domain: it reduces LM1B text-generation perplexity by 33% at its lowest-perplexity operating point, Fly Brain enhancer-design FBD by 18%, and MNIST-Binary FID by 46%. These results suggest that effective one-step discrete generation depends strongly on how data and noise are coupled before decoding. Code is available at https://github.com/pengzhangzhi/Coupling-Models.

cs.LG↗

arXiv2026

Don't Retrain, Align: Adapting Autoregressive LMs to Diffusion LMs via Representation Alignment

Diffusion language models (DLMs) have recently demonstrated capabilities that complement standard autoregressive (AR) models, particularly in non-sequential generation and bidirectional editing. Although recent work has shown that pretrained autoregressive checkpoints can be converted into diffusion language models, existing recipes primarily transfer parameters through continued denoising training with objective- and attention-level modifications. We instead ask whether the internal representation geometry learned by next-token prediction can be explicitly preserved during AR-to-DLM conversion. We hypothesize that much of the semantic structure learned by AR pretraining can transfer across generation orders, and thus DLM training should be viewed as relearning the decoding path rather than relearning language representations. To investigate this, we introduce REPR-ALIGN, a representation alignment objective that adapts a bidirectional masked diffusion model to reuse representations from a pretrained AR model of identical architecture. Concretely, we align the hidden states of the DLM to the frozen AR model at every layer using cosine similarity, while optimizing the standard masked denoising objective. This simple alignment, with no adapters and no architectural changes beyond the attention mask, yields up to 4x training acceleration in our setting and is particularly effective in low-data regimes. Our results suggest that linguistic representations can transfer across generation order, and that representation alignment provides a simple and effective technique for training diffusion language models. Code is available at https://github.com/pengzhangzhi/Open-dLLM.

cs.LG↗

arXiv2026

General Multimodal Protein Design Enables DNA-Encoding of Chemistry

Evolution is an extraordinary engine for enzymatic diversity, yet the chemistry it has explored remains a narrow slice of what DNA can encode. Deep generative models can design new proteins that bind ligands, but none have created enzymes without pre-specifying catalytic residues. We introduce DISCO (DIffusion for Sequence-structure CO-design), a multimodal model that co-designs protein sequence and 3D structure around arbitrary biomolecules, as well as inference-time scaling methods that optimize objectives across both modalities. Conditioned solely on reactive intermediates, DISCO designs diverse heme enzymes with novel active-site geometries. These enzymes catalyze new-to-nature carbene-transfer reactions, including alkene cyclopropanation, spirocyclopropanation, B-H, and C(sp$^3$)-H insertions, with high activities exceeding those of engineered enzymes. Random mutagenesis of a selected design further confirmed that enzyme activity can be improved through directed evolution. By providing a scalable route to evolvable enzymes, DISCO broadens the potential scope of genetically encodable transformations. Code is available at https://github.com/DISCO-design/DISCO.

cs.LG↗

arXiv2026

MIOFlow 2.0: A unified framework for inferring cellular stochastic dynamics from single cell and spatial transcriptomics data

Understanding cellular trajectories via time-resolved single-cell transcriptomics is vital for studying development, regeneration, and disease. A key challenge is inferring continuous trajectories from discrete snapshots. Biological complexity stems from stochastic cell fate decisions, temporal proliferation changes, and spatial environmental influences. Current methods often use deterministic interpolations treating cells in isolation, failing to capture the probabilistic branching, population shifts, and niche-dependent signaling driving real biological processes. We introduce Manifold Interpolating Optimal-Transport Flow (MIOFlow) 2.0. This framework learns biologically informed cellular trajectories by integrating manifold learning, optimal transport, and neural differential equations. It models three core processes: (1) stochasticity and branching via Neural Stochastic Differential Equations; (2) non-conservative population changes using a learned growth-rate model initialized with unbalanced optimal transport; and (3) environmental influence through a joint latent space unifying gene expression with spatial features like local cell type composition and signaling. By operating in a PHATE-distance matching autoencoder latent space, MIOFlow 2.0 ensures trajectories respect the data's intrinsic geometry. Empirical comparisons show expressive trajectory learning via neural differential equations outperforms existing generative models, including simulation-free flow matching. Validated on synthetic datasets, embryoid body differentiation, and spatially resolved axolotl brain regeneration, MIOFlow 2.0 improves trajectory accuracy and reveals hidden drivers of cellular transitions, like specific signaling niches. MIOFlow 2.0 thus bridges single-cell and spatial transcriptomics to uncover tissue-scale trajectories.

cs.LG↗

arXiv2026

MacroGuide: Topological Guidance for Macrocycle Generation

Macrocycles are ring-shaped molecules that offer a promising alternative to small-molecule drugs due to their enhanced selectivity and binding affinity against difficult targets. Despite their chemical value, they remain underexplored in generative modeling, likely owing to their scarcity in public datasets and the challenges of enforcing topological constraints in standard deep generative models. We introduce MacroGuide: Topological Guidance for Macrocycle Generation, a diffusion guidance mechanism that uses Persistent Homology to steer the sampling of pretrained molecular generative models toward the generation of macrocycles, in both unconditional and conditional (protein pocket) settings. At each denoising step, MacroGuide constructs a Vietoris-Rips complex from atomic positions and promotes ring formation by optimizing persistent homology features. Empirically, applying MacroGuide to pretrained diffusion models increases macrocycle generation rates from 1% to 99%, while matching or exceeding state-of-the-art performance on key quality metrics such as chemical validity, diversity, and PoseBusters checks.

cs.LG↗

arXiv2025

FALCON: Few-step Accurate Likelihoods for Continuous Flows

Scalable sampling of molecular states in thermodynamic equilibrium is a long-standing challenge in statistical physics. Boltzmann Generators tackle this problem by pairing a generative model, capable of exact likelihood computation, with importance sampling to obtain consistent samples under the target distribution. Current Boltzmann Generators primarily use continuous normalizing flows (CNFs) trained with flow matching for efficient training of powerful models. However, likelihood calculation for these models is extremely costly, requiring thousands of function evaluations per sample, severely limiting their adoption. In this work, we propose Few-step Accurate Likelihoods for Continuous Flows (FALCON), a method which allows for few-step sampling with a likelihood accurate enough for importance sampling applications by introducing a hybrid training objective that encourages invertibility. We show FALCON outperforms state-of-the-art normalizing flow models for molecular Boltzmann sampling and is two orders of magnitude faster than the equivalently performing CNF model.

cs.LG↗

arXiv2025

OXtal: An All-Atom Diffusion Model for Organic Crystal Structure Prediction

Accurately predicting experimentally realizable 3D molecular crystal structures from their 2D chemical graphs is a long-standing open challenge in computational chemistry called crystal structure prediction (CSP). Efficiently solving this problem has implications ranging from pharmaceuticals to organic semiconductors, as crystal packing directly governs the physical and chemical properties of organic solids. In this paper, we introduce OXtal, a large-scale 100M parameter all-atom diffusion model that directly learns the conditional joint distribution over intramolecular conformations and periodic packing. To efficiently scale OXtal, we abandon explicit equivariant architectures imposing inductive bias arising from crystal symmetries in favor of data augmentation strategies. We further propose a novel crystallization-inspired lattice-free training scheme, Stoichiometric Stochastic Shell Sampling ($S^4$), that efficiently captures long-range interactions while sidestepping explicit lattice parametrization -- thus enabling more scalable architectural choices at all-atom resolution. By leveraging a large dataset of 600K experimentally validated crystal structures (including rigid and flexible molecules, co-crystals, and solvates), OXtal achieves orders-of-magnitude improvements over prior ab initio machine learning CSP methods, while remaining orders of magnitude cheaper than traditional quantum-chemical approaches. Specifically, OXtal recovers experimental structures with conformer $\text{RMSD}_1<0.5$ {\AA} and attains over 80\% packing similarity rate, demonstrating its ability to model both thermodynamic and kinetic regularities of molecular crystallization.

cs.LG↗

arXiv2025

Foundations of Diffusion Models in General State Spaces: A Self-Contained Introduction

Although diffusion models now occupy a central place in generative modeling, introductory treatments commonly assume Euclidean data and seldom clarify their connection to discrete-state analogues. This article is a self-contained primer on diffusion over general state spaces, unifying continuous domains and discrete/categorical structures under one lens. We develop the discrete-time view (forward noising via Markov kernels and learned reverse dynamics) alongside its continuous-time limits -- stochastic differential equations (SDEs) in $\mathbb{R}^d$ and continuous-time Markov chains (CTMCs) on finite alphabets -- and derive the associated Fokker--Planck and master equations. A common variational treatment yields the ELBO that underpins standard training losses. We make explicit how forward corruption choices -- Gaussian processes in continuous spaces and structured categorical transition kernels (uniform, masking/absorbing and more) in discrete spaces -- shape reverse dynamics and the ELBO. The presentation is layered for three audiences: newcomers seeking a self-contained intuitive introduction; diffusion practitioners wanting a global theoretical synthesis; and continuous-diffusion experts looking for an analogy-first path into discrete diffusion. The result is a unified roadmap to modern diffusion methodology across continuous domains and discrete sequences, highlighting a compact set of reusable proofs, identities, and core theoretical principles.

stat.ML↗

arXiv2025

Curly Flow Matching for Learning Non-gradient Field Dynamics

Modeling the transport dynamics of natural processes from population-level observations is a ubiquitous problem in the natural sciences. Such models rely on key assumptions about the underlying process in order to enable faithful learning of governing dynamics that mimic the actual system behavior. The de facto assumption in current approaches relies on the principle of least action that results in gradient field dynamics and leads to trajectories minimizing an energy functional between two probability measures. However, many real-world systems, such as cell cycles in single-cell RNA, are known to exhibit non-gradient, periodic behavior, which fundamentally cannot be captured by current state-of-the-art methods such as flow and bridge matching. In this paper, we introduce Curly Flow Matching (Curly-FM), a novel approach that is capable of learning non-gradient field dynamics by designing and solving a Schr\"odinger bridge problem with a non-zero drift reference process -- in stark contrast to typical zero-drift reference processes -- which is constructed using inferred velocities in addition to population snapshot data. We showcase Curly-FM by solving the trajectory inference problems for single cells, computational fluid dynamics, and ocean currents with approximate velocities. We demonstrate that Curly-FM can learn trajectories that better match both the reference process and population marginals. Curly-FM expands flow matching models beyond the modeling of populations and towards the modeling of known periodic behavior in physical systems. Our code repository is accessible at: https://github.com/kpetrovicc/curly-flow-matching.git

cs.LG↗

arXiv2025

Simulation-free Structure Learning for Stochastic Dynamics

Modeling dynamical systems and unraveling their underlying causal relationships is central to many domains in the natural sciences. Various physical systems, such as those arising in cell biology, are inherently high-dimensional and stochastic in nature, and admit only partial, noisy state measurements. This poses a significant challenge for addressing the problems of modeling the underlying dynamics and inferring the network structure of these systems. Existing methods are typically tailored either for structure learning or modeling dynamics at the population level, but are limited in their ability to address both problems together. In this work, we address both problems simultaneously: we present StructureFlow, a novel and principled simulation-free approach for jointly learning the structure and stochastic population dynamics of physical systems. We showcase the utility of StructureFlow for the tasks of structure learning from interventions and dynamical (trajectory) inference of conditional population dynamics. We empirically evaluate our approach on high-dimensional synthetic systems, a set of biologically plausible simulated systems, and an experimental single-cell dataset. We show that StructureFlow can learn the structure of underlying systems while simultaneously modeling their conditional population dynamics -- a key step toward the mechanistic understanding of systems behavior.

cs.LG↗

arXiv2025

Planner Aware Path Learning in Diffusion Language Models Training

Diffusion language models have emerged as a powerful alternative to autoregressive models, enabling fast inference through more flexible and parallel generation paths. This flexibility of sampling is unlocked by new engineered sampling strategies, or planners, that select more favorable generation paths by iteratively planning - versus uniformly at random - where to denoise along the sequence. However, by modifying the reverse paths via planning, planners create an irrevocable mismatch between the uniformly random denoising paths assumed during training and planning-based inference. In this paper, we systematically investigate the mismatch of discrete diffusion training and inference under planning and theoretically prove that the standard discrete diffusion training evidence lower bound (ELBO) does not accurately describe a denoiser that uses a non-uniform planner. To address this gap, we derive a new planned evidence lower bound (P-ELBO) that incorporates planner-based reverse dynamics directly into the training objective. Using the P-ELBO, we introduce Planner Aware Path Learning (PAPL), a novel training scheme that aligns training and inference under a planned denoiser. PAPL is implemented as a simple yet effective modification to the standard masked discrete diffusion loss, making it widely applicable and easy to adopt. Empirically, we show PAPL delivers consistent gains across domains, including a 40% relative improvement in protein sequences, improved text generation with up to a 4x relative MAUVE gain, and 23% relative improvement in code generation HumanEval pass@10. Code is available at github.com/pengzhangzhi/PAPL .

cs.LG↗

arXiv2025

Amortized Sampling with Transferable Normalizing Flows

Efficient equilibrium sampling of molecular conformations remains a core challenge in computational chemistry and statistical inference. Classical approaches such as molecular dynamics or Markov chain Monte Carlo inherently lack amortization; the computational cost of sampling must be paid in full for each system of interest. The widespread success of generative models has inspired interest towards overcoming this limitation through learning sampling algorithms. Despite performing competitively with conventional methods when trained on a single system, learned samplers have so far demonstrated limited ability to transfer across systems. We demonstrate that deep learning enables the design of scalable and transferable samplers by introducing Prose, a 285 million parameter all-atom transferable normalizing flow trained on a corpus of peptide molecular dynamics trajectories up to 8 residues in length. Prose draws zero-shot uncorrelated proposal samples for arbitrary peptide systems, achieving the previously intractable transferability across sequence length, whilst retaining the efficient likelihood evaluation of normalizing flows. Through extensive empirical evaluation we demonstrate the efficacy of Prose as a proposal for a variety of sampling algorithms, finding a simple importance sampling-based fine-tuning procedure to achieve competitive performance to established methods such as sequential Monte Carlo. We open-source the Prose codebase, model weights, and training dataset, to further stimulate research into amortized sampling methods and objectives.

cs.LG↗