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Yichun He

dblp:391/0408 · DBLP profile ↗
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1ranked-venue papers
0as first author
1since 2021 · last 2025
—ORCID · none

Domains — the database's venue-derived domains; a paper can count in several

Artificial intelligence and machine learning · 1 · 1 since 2021

Expertise — from the expertise taxonomy: the topics of the expert's papers under the CCF categories. A weight counts papers with recency: 1 for a paper about the topic, 0.3 when the topic is its context, halved every five years.

Artificial intelligence
1 paper
Generative modeling · 67% Reinforcement learning · 33%
Interdisciplinary, comprehensive, and emerging computing
1 paper
Bioinformatics and computational biology · 100%

Topics — the 6 heaviest of 6, each with the papers that count most for it

TopicWeightPapersLastEvidence papers
Machine learning › Generative modeling
diffusion model
0.912025
Fine-Tuning Discrete Diffusion Models via Reward Optimization with Applications to DNA and Protein Design · ICLR 2025
Machine learning › Generative modeling › diffusion model
discrete diffusion model
0.912025
Fine-Tuning Discrete Diffusion Models via Reward Optimization with Applications to DNA and Protein Design · ICLR 2025
Machine learning › Reinforcement learning
reward maximization
0.912025
Fine-Tuning Discrete Diffusion Models via Reward Optimization with Applications to DNA and Protein Design · ICLR 2025
Bioinformatics and computational biology › synthetic biology
DNA sequence design
0.312025
Fine-Tuning Discrete Diffusion Models via Reward Optimization with Applications to DNA and Protein Design · ICLR 2025
Bioinformatics and computational biology › protein design
inverse protein folding
0.312025
Fine-Tuning Discrete Diffusion Models via Reward Optimization with Applications to DNA and Protein Design · ICLR 2025
Bioinformatics and computational biology
protein design
0.312025
Fine-Tuning Discrete Diffusion Models via Reward Optimization with Applications to DNA and Protein Design · ICLR 2025

Methods — techniques the papers use, named apart from their topics

reinforcement learning · 1.7gumbel-softmax · 1.7KL divergence · 1.7
YearPublicationVenuePosition
2025 Fine-Tuning Discrete Diffusion Models via Reward Optimization with Applications to DNA and Protein Design
abstract
Recent studies have demonstrated the strong empirical performance of diffusion models on discrete sequences (i.e., discrete diffusion models) across domains such as natural language and biological sequence generation. For example, in the protein inverse folding task, where the goal is to generate a protein sequence from a given backbone structure, conditional diffusion models have achieved impressive results in generating "natural" sequences that fold back into the original structure. However, practical design tasks often require not only modeling a conditional distribution but also optimizing specific task objectives. For instance, in the inverse folding task, we may prefer proteins with high stability. To address this, we consider the scenario where we have pre-trained discrete diffusion models that can generate "natural" sequences, as well as reward models that map sequences to task objectives. We then formulate the reward maximization problem within discrete diffusion models, analogous to reinforcement learning (RL), while minimizing the KL divergence against pre-trained diffusion models to preserve naturalness. To solve this RL problem, we propose a novel algorithm that enables direct backpropagation of rewards through entire trajectories generated by diffusion models, by making the originally non-differentiable trajectories differentiable using the Gumbel-Softmax trick. Our theoretical analysis indicates that our approach can generate sequences that are both "natural" (i.e., have a high probability under a pre-trained model) and yield high rewards. While similar tasks have been recently explored in diffusion models for continuous domains, our work addresses unique algorithmic and theoretical challenges specific to discrete diffusion models, which arise from their foundation in continuous-time Markov chains rather than Brownian motion. Finally, we demonstrate the effectiveness of our algorithm in generating DNA and protein sequences that optimize enhancer activity and protein stability, respectively, important tasks for gene therapies and protein-based therapeutics. The code is available at https://github.com/ChenyuWang-Monica/DRAKES.
Chenyu Wang 0003, Masatoshi Uehara, Yichun He, Amy Wang, Avantika Lal, Tommi S. Jaakkola, Sergey Levine, Aviv Regev, Hanchen Wang 0002, Tommaso Biancalani
ICLR3