Gabe Gomes

Daniil A. Boiko, Robert MacKnight, Gabe Gomes

Transformer-based large language models are rapidly advancing in the field of machine learning research, with applications spanning natural language, biology, chemistry, and computer programming. Extreme scaling and reinforcement learning from human feedback have significantly improved the quality of generated text, enabling these models to perform various tasks and reason about their choices. In this paper, we present an Intelligent Agent system that combines multiple large language models for autonomous design, planning, and execution of scientific experiments. We showcase the Agent's scientific research capabilities with three distinct examples, with the most complex being the successful performance of catalyzed cross-coupling reactions. Finally, we discuss the safety implications of such systems and propose measures to prevent their misuse.

Daniil A. Boiko, Thiago Reschützegger, Benjamin Sanchez-Lengeling et al.

Molecular representation is a critical element in our understanding of the physical world and the foundation for modern molecular machine learning. Previous molecular machine learning models have employed strings, fingerprints, global features, and simple molecular graphs that are inherently information-sparse representations. However, as the complexity of prediction tasks increases, the molecular representation needs to encode higher fidelity information. This work introduces a novel approach to infusing quantum-chemical-rich information into molecular graphs via stereoelectronic effects, enhancing expressivity and interpretability. Learning to predict the stereoelectronics-infused representation with a tailored double graph neural network workflow enables its application to any downstream molecular machine learning task without expensive quantum chemical calculations. We show that the explicit addition of stereoelectronic information significantly improves the performance of message-passing 2D machine learning models for molecular property prediction. We show that the learned representations trained on small molecules can accurately extrapolate to much larger molecular structures, yielding chemical insight into orbital interactions for previously intractable systems, such as entire proteins, opening new avenues of molecular design. Finally, we have developed a web application (simg.cheme.cmu.edu) where users can rapidly explore stereoelectronic information for their own molecular systems.

Alex Ning, Yen-Ling Kuo, Gabe Gomes

Latent reasoning represents a new development in Transformer language models that has shown potential in compressing reasoning lengths compared to chain-of-thought reasoning. By directly passing the information-rich previous final latent state into the next sequence, latent reasoning removes the restriction to human language tokens as the medium for reasoning. We develop adaptive-length latent reasoning models and introduce a post-SFT reinforcement-learning methodology to optimize latent reasoning length by minimizing reasoning length while maintaining accuracy. This, in turn, further reduces compute usage and raises the bar on the compressive capabilities of latent reasoning models. Experiments on the Llama 3.2 1B model and the GSM8K-Aug dataset show a $52\%$ drop in total reasoning length with no penalty to accuracy. In future work, we plan to extend to additional models and datasets, analyze relationships between training coefficients, experiment with architecture variations, and continue our knowledge distillation for latent reasoning SFT efforts. We make our code and pretrained weights available at https://github.com/apning/adaptive-latent-reasoning.

Jaspreet Pannu, Doni Bloomfield, Alex Zhu et al.

As a result of rapidly accelerating AI capabilities, over the past year, national governments and multinational bodies have announced efforts to address safety, security and ethics issues related to AI models. One high priority among these efforts is the mitigation of misuse of AI models. Many biologists have for decades sought to reduce the risks of scientific research that could lead, through accident or misuse, to high-consequence disease outbreaks. Scientists have carefully considered what types of life sciences research have the potential for both benefit and risk (dual-use), especially as scientific advances have accelerated our ability to engineer organisms and create novel variants of pathogens. Here we describe how previous experience and study by scientists and policy professionals of dual-use capabilities in the life sciences can inform risk evaluations of AI models with biological capabilities. We argue that AI model evaluations should prioritize addressing high-consequence risks (those that could cause large-scale harm to the public, such as pandemics), and that these risks should be evaluated prior to model deployment so as to allow potential biosafety and/or biosecurity measures. Scientists' experience with identifying and mitigating dual-use biological risks can help inform new approaches to evaluating biological AI models. Identifying which AI capabilities post the greatest biosecurity and biosafety concerns is necessary in order to establish targeted AI safety evaluation methods, secure these tools against accident and misuse, and avoid impeding immense potential benefits.

Brenda Nogueira, Gabe Gomes, Meng Jiang et al.

Graph-structured data is ubiquitous in scientific domains, where models often face imbalanced learning settings. In imbalanced regression, domain preferences focus on specific target value ranges that represent the most scientifically valuable cases; however, we observe a significant lack of research regarding this challenge. In this paper, we present Spectral Manifold Harmonization (SMH), a novel approach to address imbalanced regression challenges on graph-structured data by generating synthetic graph samples that preserve topological properties while focusing on the most relevant target distribution regions. Conventional methods fail in this context because they either ignore graph topology in case generation or do not target specific domain ranges, resulting in models biased toward average target values. Experimental results demonstrate the potential of SMH on chemistry and drug discovery benchmark datasets, showing consistent improvements in predictive performance for target domain ranges. Code is available at https://github.com/brendacnogueira/smh-graph-imbalance.git.

Robert MacKnight, Jose Emilio Regio, Jeffrey G. Ethier et al.

Modern optimization in experimental chemistry employs algorithmic search through black-box parameter spaces. Here we demonstrate that pre-trained knowledge in large language models (LLMs) fundamentally changes this paradigm. Using six fully enumerated categorical reaction datasets (768-5,684 experiments), we benchmark LLM-guided optimization (LLM-GO) against Bayesian optimization (BO) and random sampling. Frontier LLMs consistently match or exceed BO performance across five single-objective datasets, with advantages growing as parameter complexity increases and high-performing conditions become scarce (<5% of space). BO retains superiority only for explicit multi-objective trade-offs. To understand these contrasting behaviors, we introduce a topology-agnostic information theory framework quantifying sampling diversity throughout optimization campaigns. This analysis reveals that LLMs maintain systematically higher exploration Shannon entropy than BO across all datasets while achieving superior performance, with advantages most pronounced in solution-scarce parameter spaces where high-entropy exploration typically fails-suggesting that pre-trained domain knowledge enables more effective navigation of chemical parameter space rather than replacing structured exploration strategies. To enable transparent benchmarking and community validation, we release Iron Mind (https://gomes.andrew.cmu.edu/iron-mind), a no-code platform for side-by-side evaluation of human, algorithmic, and LLM optimization campaigns with public leaderboards and complete trajectories. Our findings establish that LLM-GO excels precisely where traditional methods struggle: complex categorical spaces requiring domain understanding rather than mathematical optimization.