# Contact-Guided 3D Genome Structure Generation of E. coli via Diffusion Transformers

arXiv: https://arxiv.org/abs/2603.07472 · HTML: https://mlsanity.com/paper/2603.07472/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Placed in Flow matching, time series and science, one of 14 directions in Diffusion models.
- Builds on 11 of its 24 references that are in the map.
- First posted on arXiv 8 Mar 2026.

## 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, 11 of 11)

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- [Classifier-Free Diffusion Guidance](https://mlsanity.com/paper/2207.12598/) (2022)
- [Scaling Rectified Flow Transformers for High-Resolution Image Synthesis](https://mlsanity.com/paper/2403.03206/) (2024)
- [Flow Straight and Fast: Learning to Generate and Transfer Data with Rectified Flow](https://mlsanity.com/paper/2209.03003/) (2022)
- [PixArt-α: Fast Training of Diffusion Transformer for Photorealistic Text-to-Image Synthesis](https://mlsanity.com/paper/2310.00426/) (2023)
- [Padding Tone: A Mechanistic Analysis of Padding Tokens in T2I Models](https://mlsanity.com/paper/2501.06751/) (2025)
- [EDiT: Efficient Diffusion Transformers with Linear Compressed Attention](https://mlsanity.com/paper/2503.16726/) (2025)
- [Diffusion Adaptive Text Embedding for Text-to-Image Diffusion Models](https://mlsanity.com/paper/2510.23974/) (2025)
- [Zero-Shot Video Deraining with Video Diffusion Models](https://mlsanity.com/paper/2511.18537/) (2025)

## Abstract (arXiv)

In this study, we present a conditional diffusion-transformer framework for generating ensembles of three-dimensional Escherichia coli genome conformations guided by Hi-C contact maps. Instead of producing a single deterministic structure, we formulate genome reconstruction as a conditional generative modeling problem that samples heterogeneous conformations whose ensemble-averaged contacts are consistent with the input Hi-C data. A synthetic dataset is constructed using coarse-grained molecular dynamics simulations to generate chromatin ensembles and corresponding Hi-C maps under circular topology. Our models operate in a latent diffusion setting with a variational autoencoder that preserves per-bin alignment and supports replication-aware representations. Hi-C information is injected through a transformer-based encoder and cross-attention, enforcing a physically interpretable one-way constraint from Hi-C to structure. The model is trained using a flow-matching objective for stable optimization. On held-out ensembles, generated structures reproduce the input Hi-C distance-decay and structural correlation metrics while maintaining substantial conformational diversity, demonstrating the effectiveness of diffusion-based generative modeling for ensemble-level 3D genome reconstruction.