# Learning Design-Score Manifold to Guide Diffusion Models for Offline Optimization

arXiv: https://arxiv.org/abs/2506.05680 · HTML: https://mlsanity.com/paper/2506.05680/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Placed in Diffusion foundations and sampling, one of 14 directions in Diffusion models.
- Builds on 51 of its 91 references that are in the map.
- First posted on arXiv 6 Jun 2025.

## Placed in

- Diffusion models / [Diffusion foundations and sampling](https://mlsanity.com/diffusion/diffusion-foundations-and-sampling/)

## Builds on (most cited first, 30 of 51)

- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [PyTorch: An Imperative Style, High-Performance Deep Learning Library](https://mlsanity.com/paper/1912.01703/) (2019)
- [Score-Based Generative Modeling through Stochastic Differential Equations](https://mlsanity.com/paper/2011.13456/) (2020)
- [Classifier-Free Diffusion Guidance](https://mlsanity.com/paper/2207.12598/) (2022)
- [Generative Adversarial Networks](https://mlsanity.com/paper/2203.00667/) (2022)
- [Conditional Generative Adversarial Nets](https://mlsanity.com/paper/1411.1784/) (2014)
- [Gradient Surgery for Multi-Task Learning](https://mlsanity.com/paper/2001.06782/) (2020)
- [GradNorm: Gradient Normalization for Adaptive Loss Balancing in Deep Multitask Networks](https://mlsanity.com/paper/1711.02257/) (2017)
- [Interpolation Consistency Training for Semi-Supervised Learning](https://mlsanity.com/paper/1903.03825/) (2019)
- [Inference-Time Scaling for Diffusion Models beyond Scaling Denoising Steps](https://mlsanity.com/paper/2501.09732/) (2025)
- [A General Framework for Inference-time Scaling and Steering of Diffusion Models](https://mlsanity.com/paper/2501.06848/) (2025)
- [Protein Design with Guided Discrete Diffusion](https://mlsanity.com/paper/2305.20009/) (2023)
- [Parallel Bayesian Optimization of Multiple Noisy Objectives with Expected Hypervolume Improvement](https://mlsanity.com/paper/2105.08195/) (2021)
- [Conditioning by adaptive sampling for robust design](https://mlsanity.com/paper/1901.10060/) (2019)
- [Accelerating Bayesian Optimization for Biological Sequence Design with Denoising Autoencoders](https://mlsanity.com/paper/2203.12742/) (2022)
- [A Flexible Framework for Multi-Objective Bayesian Optimization using Random Scalarizations](https://mlsanity.com/paper/1805.12168/) (2018)
- [Design-Bench: Benchmarks for Data-Driven Offline Model-Based Optimization](https://mlsanity.com/paper/2202.08450/) (2022)
- [Predictive Entropy Search for Multi-objective Bayesian Optimization](https://mlsanity.com/paper/1511.05467/) (2015)
- [Conservative Objective Models for Effective Offline Model-Based Optimization](https://mlsanity.com/paper/2107.06882/) (2021)
- [Model Inversion Networks for Model-Based Optimization](https://mlsanity.com/paper/1912.13464/) (2019)
- [Diffusion Models for Black-Box Optimization](https://mlsanity.com/paper/2306.07180/) (2023)
- [ROBEL: Robotics Benchmarks for Learning with Low-Cost Robots](https://mlsanity.com/paper/1909.11639/) (2019)
- [An Easy-to-use Real-world Multi-objective Optimization Problem Suite](https://mlsanity.com/paper/2009.12867/) (2020)
- [Manifold learning: what, how, and why](https://mlsanity.com/paper/2311.03757/) (2023)
- [Random Hypervolume Scalarizations for Provable Multi-Objective Black Box Optimization](https://mlsanity.com/paper/2006.04655/) (2020)
- [Multi-objective Bayesian Optimization using Pareto-frontier Entropy](https://mlsanity.com/paper/1906.00127/) (2019)
- [Joint Entropy Search for Maximally-Informed Bayesian Optimization](https://mlsanity.com/paper/2206.04771/) (2022)
- [Sample-efficient Multi-objective Molecular Optimization with GFlowNets](https://mlsanity.com/paper/2302.04040/) (2023)
- [RoMA: Robust Model Adaptation for Offline Model-based Optimization](https://mlsanity.com/paper/2110.14188/) (2021)
- [Offline Model-Based Optimization via Normalized Maximum Likelihood Estimation](https://mlsanity.com/paper/2102.07970/) (2021)

## Built on by (most cited first, 1 of 1)

- [On the Learnability of Offline Model-Based Optimization: A Ranking Perspective](https://mlsanity.com/paper/2603.04000/) (2026)

## Abstract (arXiv)

Optimizing complex systems, from discovering therapeutic drugs to designing high-performance materials, remains a fundamental challenge across science and engineering, as the underlying rules are often unknown and costly to evaluate. Offline optimization aims to optimize designs for target scores using pre-collected datasets without system interaction. However, conventional approaches may fail beyond training data, predicting inaccurate scores and generating inferior designs. This paper introduces ManGO, a diffusion-based framework that learns the design-score manifold, capturing the design-score interdependencies holistically. Unlike existing methods that treat design and score spaces in isolation, ManGO unifies forward prediction and backward generation, attaining generalization beyond training data. Key to this is its derivative-free guidance for conditional generation, coupled with adaptive inference-time scaling that dynamically optimizes denoising paths. Extensive evaluations demonstrate that ManGO outperforms 24 single- and 10 multi-objective optimization methods across diverse domains, including synthetic tasks, robot control, material design, DNA sequence, and real-world engineering optimization.