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Dirichlet Flow Matching with Applications to DNA Sequence Design (2402.05841v2)

Published 8 Feb 2024 in q-bio.BM and cs.LG

Abstract: 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.

Citations (28)

Summary

  • The paper introduces Dirichlet Flow Matching, a method that leverages Dirichlet distributions to handle discrete generative modeling on the probability simplex.
  • It uses mixtures of Dirichlet distributions to overcome discontinuities in traditional flow matching and enables efficient, one-step DNA sequence sampling.
  • Experimental results demonstrate significant improvements in promoter and enhancer DNA sequence design, outperforming autoregressive models in key metrics like FBD and MSE.

Dirichlet Flow Matching with Applications to DNA Sequence Design

The paper presents a novel approach to discrete generative modeling through the development of Dirichlet Flow Matching (Dirichlet FM), a method designed to better handle discrete categorical data than existing autoregressive models or linearly matched discrete diffusion models. It strategically employs Dirichlet distributions to manage the probability paths on the simplex, thereby overcoming challenges such as the discontinuities and pathologies associated with naive linear flow matching.

Motivation and Approach

Traditional flow matching models have been confined primarily to continuous spaces, limiting their efficacy for applications that involve discrete categorical data spaces like text generation and biological sequence design. The authors propose Dirichlet FM as a solution, which introduces a generative modeling framework leveraging mixtures of Dirichlet distributions. This methodology enables smooth interpolation between noise and data distributions, thereby facilitating efficient sampling from the model.

The method frames generative modeling as a transport problem on the probability simplex. By determining a connection between mixture scores and flow vector fields, Dirichlet FM allows for both classifier and classifier-free guidance. This is significant because it provides controlled guidance toward a desired generation target, an essential feature in many practical applications.

Results and Numerical Strength

The authors demonstrate the practical applications of Dirichlet FM through DNA sequence generation tasks, showing superior distributional metrics and target design achievement compared to existing methodologies. Specifically, Dirichlet FM exhibits substantial improvements in Fréchet Biological Distance (FBD) and mean squared error (MSE) for promoter DNA sequence design and enhancer DNA generation tasks.

One particularly impressive numerical result is the enhancement of distributional similarity scores on tasks such as generating sequences from complex DNA datasets. For instance, the Dirichlet FM significantly outperforms autoregressive models in capturing data distributions, achieving FBD values as low as 1.9 in melanoma DNA sequences compared to 36.0 using autoregressive methods.

Theoretical Implications

From a theoretical perspective, Dirichlet FM makes a compelling case for the utility of leveraging smoothly varying Dirichlet distributions over the simplex. This choice mitigates the support contraction observed in linear flow matching approaches, allowing Dirichlet FM to maintain a broad support over the simplex at all times during the generative process. This approach could prompt future research into alternative applications of Dirichlet distributions or similar probabilistic models for other types of discrete data.

Practical Implications

Practically, the introduction of Dirichlet FM could influence the design of generative models beyond discrete data, including potential applications in areas like genomics and other biological sequences where controlled generation is necessary. The ability to distill the Dirichlet FM model to enable one-step sequence generation represents a substantial computational efficiency improvement, suggesting valuable applications in real-time systems where speed is critical.

Future Speculations

Looking forward, the research opens new avenues in discrete data modeling and optimization, particularly in biological applications where the need for speed and accuracy in sequence design is paramount. Furthermore, applying Dirichlet FM to complex data structures could lead to advancements in other domains, such as protein folding, natural language processing, and any other area where data can be represented in high-dimensional probability simplices.

In summary, the paper successfully extends the boundaries of traditional flow matching and discrete diffusion models by embedding a theoretic understanding of continuous space flows into discrete data paradigms. The results point to both immediate applications and future explorations in leveraging Dirichlet and related probabilistic models to overcome the limitations of current methodologies in discrete generative modeling.

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