Ctrl-DNA: Controllable Cell-Type-Specific Regulatory DNA Design via Constrained RL

Designing regulatory DNA sequences that achieve precise cell-type-specific gene expression is crucial for advancements in synthetic biology, gene therapy and precision medicine. Although transformer-based language models (LMs) can effectively capture patterns in regulatory DNA, their generative approaches often struggle to produce novel sequences with reliable cell-specific activity. Here, we introduce Ctrl-DNA, a novel constrained reinforcement learning (RL) framework tailored for designing regulatory DNA sequences with controllable cell-type specificity. By formulating regulatory sequence design as a biologically informed constrained optimization problem, we apply RL to autoregressive genomic LMs, enabling the models to iteratively refine sequences that maximize regulatory activity in targeted cell types while constraining off-target effects. Our evaluation on human promoters and enhancers demonstrates that Ctrl-DNA consistently outperforms existing generative and RL-based approaches, generating high-fitness regulatory sequences and achieving state-of-the-art cell-type specificity. Moreover, Ctrl-DNA-generated sequences capture key cell-type-specific transcription factor binding sites (TFBS), short DNA motifs recognized by regulatory proteins that control gene expression, demonstrating the biological plausibility of the generated sequences.

Dynamic Portfolio Optimization via Augmented DDPG with Quantum Price Levels-Based Trading Strategy

With the development of deep learning, Dynamic Portfolio Optimization (DPO) problem has received a lot of attention in recent years, not only in the field of finance but also in the field of deep learning. Some advanced research in recent years has proposed the application of Deep Reinforcement Learning (DRL) to the DPO problem, which demonstrated to be more advantageous than supervised learning in solving the DPO problem. However, there are still certain unsolved issues: 1) DRL algorithms usually have the problems of slow learning speed and high sample complexity, which is especially problematic when dealing with complex financial data. 2) researchers use DRL simply for the purpose of obtaining high returns, but pay little attention to the problem of risk control and trading strategy, which will affect the stability of model returns. In order to address these issues, in this study we revamped the intrinsic structure of the model based on the Deep Deterministic Policy Gradient (DDPG) and proposed the Augmented DDPG model. Besides, we also proposed an innovative risk control strategy based on Quantum Price Levels (QPLs) derived from Quantum Finance Theory (QFT). Our experimental results revealed that our model has better profitability as well as risk control ability with less sample complexity in the DPO problem compared to the baseline models.