# Absorb & Escape: Overcoming Single Model Limitations in Generating Genomic Sequences

arXiv: https://arxiv.org/abs/2410.21345 · HTML: https://mlsanity.com/paper/2410.21345/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 14 of its 39 references that are in the map.
- First posted on arXiv 28 Oct 2024.

## Builds on (most cited first, 14 of 14)

- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [High-Resolution Image Synthesis with Latent Diffusion Models](https://mlsanity.com/paper/2112.10752/) (2021)
- [Denoising Diffusion Implicit Models](https://mlsanity.com/paper/2010.02502/) (2020)
- [Deep Unsupervised Learning using Nonequilibrium Thermodynamics](https://mlsanity.com/paper/1503.03585/) (2015)
- [SGDR: Stochastic Gradient Descent with Warm Restarts](https://mlsanity.com/paper/1608.03983/) (2016)
- [Structured Denoising Diffusion Models in Discrete State-Spaces](https://mlsanity.com/paper/2107.03006/) (2021)
- [Diffusion-LM Improves Controllable Text Generation](https://mlsanity.com/paper/2205.14217/) (2022)
- [Reduce, Reuse, Recycle: Compositional Generation with Energy-Based Diffusion Models and MCMC](https://mlsanity.com/paper/2302.11552/) (2023)
- [HyenaDNA: Long-Range Genomic Sequence Modeling at Single Nucleotide Resolution](https://mlsanity.com/paper/2306.15794/) (2023)
- [Dirichlet Flow Matching with Applications to DNA Sequence Design](https://mlsanity.com/paper/2402.05841/) (2024)
- [Dirichlet Diffusion Score Model for Biological Sequence Generation](https://mlsanity.com/paper/2305.10699/) (2023)
- [PLANNER: Generating Diversified Paragraph via Latent Language Diffusion Model](https://mlsanity.com/paper/2306.02531/) (2023)
- [Compositional Generative Modeling: A Single Model is Not All You Need](https://mlsanity.com/paper/2402.01103/) (2024)
- [Generating and designing DNA with deep generative models](https://mlsanity.com/paper/1712.06148/) (2017)

## Abstract (arXiv)

Abstract Recent advances in immunology and synthetic biology have accelerated the development of deep generative methods for DNA sequence design. Two dominant approaches in this field are AutoRegressive (AR) models and Diffusion Models (DMs). However, genomic sequences are functionally heterogeneous, consisting of multiple connected regions (e.g., Promoter Regions, Exons, and Introns) where elements within each region come from the same probability distribution, but the overall sequence is non-homogeneous. This heterogeneous nature presents challenges for a single model to accurately generate genomic sequences. In this paper, we analyze the properties of AR models and DMs in heterogeneous genomic sequence generation, pointing out crucial limitations in both methods: (i) AR models capture the underlying distribution of data by factorizing and learning the transition probability but fail to capture the global property of DNA sequences. (ii) DMs learn to recover the global distribution but tend to produce errors at the base pair level. To overcome the limitations of both approaches, we propose a post-training sampling method, termed Absorb & Escape (A&E) to perform compositional generation from AR models and DMs. This approach starts with samples generated by DMs and refines the sample quality using an AR model through the alternation of the Absorb and Escape steps. To assess the quality of generated sequences, we conduct extensive experiments on 15 species for conditional and unconditional DNA generation. The experiment results from motif distribution, diversity checks, and genome integration tests unequivocally show that A&E outperforms state-of-the-art AR models and DMs in genomic sequence generation.