According to the World Health Organization (WHO), over 2.3 million women were diagnosed with breast cancer in 2020, making it the most diagnosed cancer worldwide and the leading cause of cancer-related deaths among women (WHO, 2021). The incidence of breast cancer is rising by around 3% per year, with higher mortality rates observed in lower-income countries due to limited access to early screening and treatment. In wealthier nations, 1 in 12 women are diagnosed with breast cancer, whereas in lower-income countries, the rate is 1 in 27. More concerning is the disparity in mortality--1 in 48 women die from breast cancer in low-income countries compared to 1 in 71 in high-income countries (WHO, 2022). In sub-Saharan Africa, breast cancer now has the highest mortality rate among all cancers affecting women, surpassing cervical cancer.

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.

The ultimate goal of multi-objective optimization (MO) is to assist human decision-makers (DMs) in identifying solutions of interest (SOI) that optimally reconcile multiple objectives according to their preferences. Yet, current PBEMO approaches are prone to be inefficient and misaligned with the DM's true aspirations, especially when inadvertently exploiting mis-calibrated reward models. This is further exacerbated when considering the stochastic nature of human feedback. This paper proposes a novel framework that navigates MO to SOI by directly leveraging human feedback without being restricted by a predefined reward model nor cumbersome model selection. Specifically, we developed a clustering-based stochastic dueling bandits algorithm that strategically scales well to high-dimensional dueling bandits, and achieves a regret of \mathcal{O}(K 2\log T), where K is the number of clusters and T is the number of rounds.

As part of the effort to understand how the brain learns, ongoing research seeks to combine biological knowledge with current artificial intelligence (AI) modeling in an attempt to find an efficient biologically plausible learning scheme. Current models often use a cortical-like combination of bottom-up (BU) and top-down (TD) processing, where the TD part carries feedback signals for learning. However, in the visual cortex, the TD pathway plays a second major role in visual attention, by guiding the visual process toward locations and tasks of interest. A biological model should therefore integrate both learning and visual guidance. We introduce a model that uses a cortical-like combination of BU and TD processing that naturally integrates the two major functions of the TD stream.

The omnipresence of NP-hard combinatorial optimization problems (COPs) compels domain experts to engage in trial-and-error heuristic design. The long-standing endeavor of design automation has gained new momentum with the rise of large language models (LLMs). This paper introduces Language Hyper-Heuristics (LHHs), an emerging variant of Hyper-Heuristics that leverages LLMs for heuristic generation, featuring minimal manual intervention and open-ended heuristic spaces. To empower LHHs, we present Reflective Evolution (ReEvo), a novel integration of evolutionary search for efficiently exploring the heuristic space, and LLM reflections to provide verbal gradients within the space.

Solving NP-hard combinatorial optimization problems (COPs) (e.g., traveling salesman problems (TSPs) and capacitated vehicle routing problems (CVRPs)) in practice traditionally involves handcrafting heuristics or specifying a search space for finding effective heuristics. The main challenges from these approaches, however, are the sheer amount of domain knowledge and implementation efforts required from human experts. Recently, significant progress has been made to address these challenges, particularly by using large language models (LLMs) to design heuristics within some predetermined generalized algorithmic framework (GAF, e.g., ant colony optimization and guided local search) for building key functions/components (e.g., a priori information on how promising it is to include each edge in a solution for TSP and CVRP). Although existing methods leveraging this idea have shown to yield impressive optimization performance, they are not fully end-to-end and still require considerable manual interventions. In this paper, we propose a novel end-to-end framework, named RedAHD, that enables these LLM-based heuristic design methods to operate without the need of GAFs. More specifically, RedAHD employs LLMs to automate the process of reduction, i.e., transforming the COP at hand into similar COPs that are better-understood, from which LLM-based heuristic design methods can design effective heuristics for directly solving the transformed COPs and, in turn, indirectly solving the original COP. Our experimental results, evaluated on six COPs, show that RedAHD is capable of designing heuristics with competitive or improved results over the state-of-the-art methods with minimal human involvement.

Deep reinforcement learning (DRL) has been widely used for dynamic algorithm configuration, particularly in evolutionary computation, which benefits from the adaptive update of parameters during the algorithmic execution. However, applying DRL to algorithm configuration for multi-objective combinatorial optimization (MOCO) problems remains relatively unexplored. This paper presents a novel graph neural network (GNN) based DRL to configure multi-objective evolutionary algorithms. We model the dynamic algorithm configuration as a Markov decision process, representing the convergence of solutions in the objective space by a graph, with their embeddings learned by a GNN to enhance the state representation. Experiments on diverse MOCO challenges indicate that our method outperforms traditional and DRL-based algorithm configuration methods in terms of efficacy and adaptability. It also exhibits advantageous generalizability across objective types and problem sizes, and applicability to different evolutionary computation methods.

The safety and reliability of Automated Driving Systems (ADS) are paramount, necessitating rigorous testing methodologies to uncover potential failures before deployment. Traditional testing approaches often prioritize either natural scenario sampling or safety-critical scenario generation, resulting in overly simplistic or unrealistic hazardous tests. In practice, the demand for natural scenarios (e.g., when evaluating the ADS's reliability in real-world conditions), critical scenarios (e.g., when evaluating safety in critical situations), or somewhere in between (e.g., when testing the ADS in regions with less civilized drivers) varies depending on the testing objectives. To address this issue, we propose the On-demand Scenario Generation (OSG) Framework, which generates diverse scenarios with varying risk levels. Achieving the goal of OSG is challenging due to the complexity of quantifying the criticalness and naturalness stemming from intricate vehicle-environment interactions, as well as the need to maintain scenario diversity across various risk levels. OSG learns from real-world traffic datasets and employs a Risk Intensity Regulator to quantitatively control the risk level. It also leverages an improved heuristic search method to ensure scenario diversity. We evaluate OSG on the Carla simulators using various ADSs. We verify OSG's ability to generate scenarios with different risk levels and demonstrate its necessity by comparing accident types across risk levels. With the help of OSG, we are now able to systematically and objectively compare the performance of different ADSs based on different risk levels.

The performance of battery materials is determined by their composition and the processing conditions employed during commercial-scale fabrication, where raw materials undergo complex processing steps with various additives to yield final products. As the complexity of these parameters expands with the development of industry, conventional one-factor-at-a-time (OFAT) experiment becomes old fashioned. While domain expertise aids in parameter optimization, this traditional approach becomes increasingly vulnerable to cognitive limitations and anthropogenic biases as the complexity of factors grows. Herein, we introduce an iterative machine learning (ML) framework that integrates active learning to guide targeted experimentation and facilitate incremental model refinement. This method systematically leverages comprehensive experimental observations, including both successful and unsuccessful results, effectively mitigating human-induced biases and alleviating data scarcity. Consequently, it significantly accelerates exploration within the high-dimensional design space. Our results demonstrate that active-learning-driven experimentation markedly reduces the total number of experimental cycles necessary, underscoring the transformative potential of ML-based strategies in expediting battery material optimization.

Reinforcement Learning (RL) controllers have demonstrated remarkable performance in complex robot control tasks. However, the presence of reality gap often leads to poor performance when deploying policies trained in simulation directly onto real robots. Previous sim-to-real algorithms like Domain Randomization (DR) requires domain-specific expertise and suffers from issues such as reduced control performance and high training costs. In this work, we introduce Evolutionary Adversarial Simulator Identification (EASI), a novel approach that combines Generative Adversarial Network (GAN) and Evolutionary Strategy (ES) to address sim-to-real challenges. Specifically, we consider the problem of sim-to-real as a search problem, where ES acts as a generator in adversarial competition with a neural network discriminator, aiming to find physical parameter distributions that make the state transitions between simulation and reality as similar as possible.