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

• URL: http://arxiv.org/abs/2603.07472v1
• Date: Sun, 08 Mar 2026 05:19:04 GMT
• Title: Contact-Guided 3D Genome Structure Generation of E. coli via Diffusion Transformers
• Abstract summary: We formulate genome reconstruction as a conditional generative modeling problem.<n>A synthetic dataset is constructed using coarse-grained molecular dynamics simulations.<n>Our models operate in a latent diffusion setting with a variational autoencoder.<n>On held-out ensembles, generated structures reproduce the input Hi-C distance-decay and structural correlation metrics.
• Score: 4.9416904219463165
• License: http://arxiv.org/licenses/nonexclusive-distrib/1.0/
• Abstract: 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.

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