SPROUT: Steered Plant Promoter Editing via Rollout-Guided Utility Tilting of Edit Flows

Elizabeth H Mahood, Pranam Chatterjee

Keywords: plant promoter design, cis-regulatory elements, multi-objective optimization, discrete flow matching

TL;DR: SPROUT steers Edit Flows with multi-objective rollout guidance to edit plant promoters for stronger expression while preserving tissue, developmental, and treatment context.

Abstract: Engineering plant cis-regulatory elements (CREs) has high-impact applications in domains including agriculture, bioremediation, and bioengineering. Existing CRE engineering frameworks typically use either naive generative models, including random sequence generation or genetic algorithms, and/or reductive descriptions of expression context. The common formulation for cell-type specific expression -- expression enrichment in one cell type over another -- ignores all other cell types and axes of expression. For plant promoters, functional utility depends upon controlling a richer expression context across tissues, developmental stages, and environmental conditions. We thus propose **SPROUT**, an alternative formulation for CRE engineering based on **S**teered plant **P**romoter editing via **RO**llout-guided **U**tility **T**ilting of Edit Flows, pairing a recently introduced discrete flow matching framework for variable-length sequence editing with multi-objective optimization across oracles predicting expression context and strength. We evaluate SPROUT against the common formulations and show that our Edit Flow-based formulation produces more realistic sequences than random generation, while optimization with oracles trained on only two conditions does not fully constrain other expression axes.

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Submission Number: 158