# Dirichlet Flow Matching with Applications to DNA Sequence Design

arXiv: https://arxiv.org/abs/2402.05841 · HTML: https://mlsanity.com/paper/2402.05841/

## Key facts

- Cited by 115 papers in the map (data through 14 Oct 2026).
- Placed in Flow matching, time series and science, one of 14 directions in Diffusion models.
- Builds on 33 of its 47 references that are in the map.
- First posted on arXiv 8 Feb 2024.

## Placed in

- Diffusion models / [Flow matching, time series and science](https://mlsanity.com/diffusion/flow-matching-time-series-and-science/)

## Builds on (most cited first, 30 of 33)

- [High-Resolution Image Synthesis with Latent Diffusion Models](https://mlsanity.com/paper/2112.10752/) (2021)
- [Score-Based Generative Modeling through Stochastic Differential Equations](https://mlsanity.com/paper/2011.13456/) (2020)
- [Diffusion Models Beat GANs on Image Synthesis](https://mlsanity.com/paper/2105.05233/) (2021)
- [Photorealistic Text-to-Image Diffusion Models with Deep Language Understanding](https://mlsanity.com/paper/2205.11487/) (2022)
- [Classifier-Free Diffusion Guidance](https://mlsanity.com/paper/2207.12598/) (2022)
- [Flow Matching for Generative Modeling](https://mlsanity.com/paper/2210.02747/) (2022)
- [Generative Modeling by Estimating Gradients of the Data Distribution](https://mlsanity.com/paper/1907.05600/) (2019)
- [Flow Straight and Fast: Learning to Generate and Transfer Data with Rectified Flow](https://mlsanity.com/paper/2209.03003/) (2022)
- [Consistency Models](https://mlsanity.com/paper/2303.01469/) (2023)
- [Structured Denoising Diffusion Models in Discrete State-Spaces](https://mlsanity.com/paper/2107.03006/) (2021)
- [One-step Diffusion with Distribution Matching Distillation](https://mlsanity.com/paper/2311.18828/) (2023)
- [Building Normalizing Flows with Stochastic Interpolants](https://mlsanity.com/paper/2209.15571/) (2022)
- [Improving and generalizing flow-based generative models with minibatch optimal transport](https://mlsanity.com/paper/2302.00482/) (2023)
- [DiGress: Discrete Denoising diffusion for graph generation](https://mlsanity.com/paper/2209.14734/) (2022)
- [A Continuous Time Framework for Discrete Denoising Models](https://mlsanity.com/paper/2205.14987/) (2022)
- [Analog Bits: Generating Discrete Data using Diffusion Models with Self-Conditioning](https://mlsanity.com/paper/2208.04202/) (2022)
- [Multisample Flow Matching: Straightening Flows with Minibatch Couplings](https://mlsanity.com/paper/2304.14772/) (2023)
- [Flow Matching on General Geometries](https://mlsanity.com/paper/2302.03660/) (2023)
- [Continuous diffusion for categorical data](https://mlsanity.com/paper/2211.15089/) (2022)
- [Autoregressive Diffusion Models](https://mlsanity.com/paper/2110.02037/) (2021)
- [Fr'echet ChemNet Distance: A metric for generative models for molecules in drug discovery](https://mlsanity.com/paper/1803.09518/) (2018)
- [SSD-LM: Semi-autoregressive Simplex-based Diffusion Language Model for Text Generation and Modular Control](https://mlsanity.com/paper/2210.17432/) (2022)
- [Flow Matching in Latent Space](https://mlsanity.com/paper/2307.08698/) (2023)
- [SE(3)-Stochastic Flow Matching for Protein Backbone Generation](https://mlsanity.com/paper/2310.02391/) (2023)
- [Guided Flows for Generative Modeling and Decision Making](https://mlsanity.com/paper/2311.13443/) (2023)
- [Restart Sampling for Improving Generative Processes](https://mlsanity.com/paper/2306.14878/) (2023)
- [Dirichlet Diffusion Score Model for Biological Sequence Generation](https://mlsanity.com/paper/2305.10699/) (2023)
- [Projection onto the probability simplex: An efficient algorithm with a simple proof, and an application](https://mlsanity.com/paper/1309.1541/) (2013)
- [Categorical SDEs with Simplex Diffusion](https://mlsanity.com/paper/2210.14784/) (2022)
- [Protein Discovery with Discrete Walk-Jump Sampling](https://mlsanity.com/paper/2306.12360/) (2023)

## Built on by (most cited first, 30 of 115)

- [Discrete Flow Matching](https://mlsanity.com/paper/2407.15595/) (2024)
- [Simple Guidance Mechanisms for Discrete Diffusion Models](https://mlsanity.com/paper/2412.10193/) (2024)
- [Derivative-Free Guidance in Continuous and Discrete Diffusion Models with Soft Value-Based Decoding](https://mlsanity.com/paper/2408.08252/) (2024)
- [Unlocking Guidance for Discrete State-Space Diffusion and Flow Models](https://mlsanity.com/paper/2406.01572/) (2024)
- [Consistency Flow Matching: Defining Straight Flows with Velocity Consistency](https://mlsanity.com/paper/2407.02398/) (2024)
- [Understanding Reinforcement Learning-Based Fine-Tuning of Diffusion Models: A Tutorial and Review](https://mlsanity.com/paper/2407.13734/) (2024)
- [PnP-Flow: Plug-and-Play Image Restoration with Flow Matching](https://mlsanity.com/paper/2410.02423/) (2024)
- [Variational Flow Matching for Graph Generation](https://mlsanity.com/paper/2406.04843/) (2024)
- [Fine-Tuning Discrete Diffusion Models via Reward Optimization with Applications to DNA and Protein Design](https://mlsanity.com/paper/2410.13643/) (2024)
- [Fisher Flow Matching for Generative Modeling over Discrete Data](https://mlsanity.com/paper/2405.14664/) (2024)
- [Mixed Continuous and Categorical Flow Matching for 3D De Novo Molecule Generation](https://mlsanity.com/paper/2404.19739/) (2024)
- [Generative Modeling of Molecular Dynamics Trajectories](https://mlsanity.com/paper/2409.17808/) (2024)
- [How Discrete and Continuous Diffusion Meet: Comprehensive Analysis of Discrete Diffusion Models via a Stochastic Integral Framework](https://mlsanity.com/paper/2410.03601/) (2024)
- [Categorical Flow Matching on Statistical Manifolds](https://mlsanity.com/paper/2405.16441/) (2024)
- [Fast Solvers for Discrete Diffusion Models: Theory and Applications of High-Order Algorithms](https://mlsanity.com/paper/2502.00234/) (2025)
- [Categorical Flow Maps](https://mlsanity.com/paper/2602.12233/) (2026)
- [Accelerating Diffusion Models with Parallel Sampling: Inference at Sub-Linear Time Complexity](https://mlsanity.com/paper/2405.15986/) (2024)
- [SemlaFlow -- Efficient 3D Molecular Generation with Latent Attention and Equivariant Flow Matching](https://mlsanity.com/paper/2406.07266/) (2024)
- [Fine-Tuning Discrete Diffusion Models with Policy Gradient Methods](https://mlsanity.com/paper/2502.01384/) (2025)
- [PepTune: De Novo Generation of Therapeutic Peptides with Multi-Objective-Guided Discrete Diffusion](https://mlsanity.com/paper/2412.17780/) (2024)
- [Continuously Augmented Discrete Diffusion model for Categorical Generative Modeling](https://mlsanity.com/paper/2510.01329/) (2025)
- [Time Is a Feature: Exploiting Temporal Dynamics in Diffusion Language Models](https://mlsanity.com/paper/2508.09138/) (2025)
- [Continuous Diffusion Model for Language Modeling](https://mlsanity.com/paper/2502.11564/) (2025)
- [Discrete Flow Maps](https://mlsanity.com/paper/2604.09784/) (2026)
- [Wasserstein Flow Matching: Generative modeling over families of distributions](https://mlsanity.com/paper/2411.00698/) (2024)
- [WyckoffDiff -- A Generative Diffusion Model for Crystal Symmetry](https://mlsanity.com/paper/2502.06485/) (2025)
- [Bridging Model-Based Optimization and Generative Modeling via Conservative Fine-Tuning of Diffusion Models](https://mlsanity.com/paper/2405.19673/) (2024)
- [Reward-Guided Iterative Refinement in Diffusion Models at Test-Time with Applications to Protein and DNA Design](https://mlsanity.com/paper/2502.14944/) (2025)
- [Training-Free Guidance Beyond Differentiability: Scalable Path Steering with Tree Search in Diffusion and Flow Models](https://mlsanity.com/paper/2502.11420/) (2025)
- [α-Flow: A Unified Framework for Continuous-State Discrete Flow Matching Models](https://mlsanity.com/paper/2504.10283/) (2025)

## Abstract (arXiv)

Discrete diffusion or flow models could enable faster and more controllable sequence generation than autoregressive models. We show that na"ive linear flow matching on the simplex is insufficient toward this goal since it suffers from discontinuities in the training target and further pathologies. To overcome this, we develop Dirichlet flow matching on the simplex based on mixtures of Dirichlet distributions as probability paths. In this framework, we derive a connection between the mixtures' scores and the flow's vector field that allows for classifier and classifier-free guidance. Further, we provide distilled Dirichlet flow matching, which enables one-step sequence generation with minimal performance hits, resulting in O(L) speedups compared to autoregressive models. On complex DNA sequence generation tasks, we demonstrate superior performance compared to all baselines in distributional metrics and in achieving desired design targets for generated sequences. Finally, we show that our classifier-free guidance approach improves unconditional generation and is effective for generating DNA that satisfies design targets. Code is available at https://github.com/HannesStark/dirichlet-flow-matching.