M$^{3}$-20M: A Large-Scale Multi-Modal Molecule Dataset for AI-driven Drug Design and Discovery

This paper introduces M$^{3}$-20M, a large-scale Multi-Modal Molecular dataset that contains over 20 million molecules. Designed to support AI-driven drug design and discovery, M$^{3}$-20M is 71 times more in the number of molecules than the largest existing dataset, providing an unprecedented scale that can highly benefit training or fine-tuning large (language) models with superior performance for drug design and discovery. This dataset integrates one-dimensional SMILES, two-dimensional molecular graphs, three-dimensional molecular structures, physicochemical properties, and textual descriptions collected through web crawling and generated by using GPT-3.5, offering a comprehensive view of each molecule. To demonstrate the power of M$^{3}$-20M in drug design and discovery, we conduct extensive experiments on two key tasks: molecule generation and molecular property prediction, using large language models including GLM4, GPT-3.5, and GPT-4. Our experimental results show that M$^{3}$-20M can significantly boost model performance in both tasks. Specifically, it enables the models to generate more diverse and valid molecular structures and achieve higher property prediction accuracy than the existing single-modal datasets, which validates the value and potential of M$^{3}$-20M in supporting AI-driven drug design and discovery. The dataset is available at \url{https://github.com/bz99bz/M-3}.

Identifiable Exchangeable Mechanisms for Causal Structure and Representation Learning

Identifying latent representations or causal structures is important for good generalization and downstream task performance. However, both fields have been developed rather independently. We observe that several methods in both representation and causal structure learning rely on the same data-generating process (DGP), namely, exchangeable but not i.i.d. (independent and identically distributed) data. We provide a unified framework, termed Identifiable Exchangeable Mechanisms (IEM), for representation and structure learning under the lens of exchangeability. IEM provides new insights that let us relax the necessary conditions for causal structure identification in exchangeable non--i.i.d. data. We also demonstrate the existence of a duality condition in identifiable representation learning, leading to new identifiability results. We hope this work will pave the way for further research in causal representation learning.

Do Finetti: On Causal Effects for Exchangeable Data

We study causal effect estimation in a setting where the data are not i.i.d. (independent and identically distributed). We focus on exchangeable data satisfying an assumption of independent causal mechanisms. Traditional causal effect estimation frameworks, e.g., relying on structural causal models and do-calculus, are typically limited to i.i.d. data and do not extend to more general exchangeable generative processes, which naturally arise in multi-environment data. To address this gap, we develop a generalized framework for exchangeable data and introduce a truncated factorization formula that facilitates both the identification and estimation of causal effects in our setting. To illustrate potential applications, we introduce a causal P\'olya urn model and demonstrate how intervention propagates effects in exchangeable data settings. Finally, we develop an algorithm that performs simultaneous causal discovery and effect estimation given multi-environment data.

Learning Beyond Pattern Matching? Assaying Mathematical Understanding in LLMs

We are beginning to see progress in language model assisted scientific discovery. Motivated by the use of LLMs as a general scientific assistant, this paper assesses the domain knowledge of LLMs through its understanding of different mathematical skills required to solve problems. In particular, we look at not just what the pre-trained model already knows, but how it learned to learn from information during in-context learning or instruction-tuning through exploiting the complex knowledge structure within mathematics. Motivated by the Neural Tangent Kernel (NTK), we propose \textit{NTKEval} to assess changes in LLM's probability distribution via training on different kinds of math data. Our systematic analysis finds evidence of domain understanding during in-context learning. By contrast, certain instruction-tuning leads to similar performance changes irrespective of training on different data, suggesting a lack of domain understanding across different skills.

Metacognitive Capabilities of LLMs: An Exploration in Mathematical Problem Solving

Metacognitive knowledge refers to humans' intuitive knowledge of their own thinking and reasoning processes. Today's best LLMs clearly possess some reasoning processes. The paper gives evidence that they also have metacognitive knowledge, including ability to name skills and procedures to apply given a task. We explore this primarily in context of math reasoning, developing a prompt-guided interaction procedure to get a powerful LLM to assign sensible skill labels to math questions, followed by having it perform semantic clustering to obtain coarser families of skill labels. These coarse skill labels look interpretable to humans. To validate that these skill labels are meaningful and relevant to the LLM's reasoning processes we perform the following experiments. (a) We ask GPT-4 to assign skill labels to training questions in math datasets GSM8K and MATH. (b) When using an LLM to solve the test questions, we present it with the full list of skill labels and ask it to identify the skill needed. Then it is presented with randomly selected exemplar solved questions associated with that skill label. This improves accuracy on GSM8k and MATH for several strong LLMs, including code-assisted models. The methodology presented is domain-agnostic, even though this article applies it to math problems.

DS-Agent: Automated Data Science by Empowering Large Language Models with Case-Based Reasoning

In this work, we investigate the potential of large language models (LLMs) based agents to automate data science tasks, with the goal of comprehending task requirements, then building and training the best-fit machine learning models. Despite their widespread success, existing LLM agents are hindered by generating unreasonable experiment plans within this scenario. To this end, we present DS-Agent, a novel automatic framework that harnesses LLM agent and case-based reasoning (CBR). In the development stage, DS-Agent follows the CBR framework to structure an automatic iteration pipeline, which can flexibly capitalize on the expert knowledge from Kaggle, and facilitate consistent performance improvement through the feedback mechanism. Moreover, DS-Agent implements a low-resource deployment stage with a simplified CBR paradigm to adapt past successful solutions from the development stage for direct code generation, significantly reducing the demand on foundational capabilities of LLMs. Empirically, DS-Agent with GPT-4 achieves an unprecedented 100% success rate in the development stage, while attaining 36% improvement on average one pass rate across alternative LLMs in the deployment stage. In both stages, DS-Agent achieves the best rank in performance, costing \$1.60 and \$0.13 per run with GPT-4, respectively. Our code is open-sourced at https://github.com/guosyjlu/DS-Agent.

CausalCite: A Causal Formulation of Paper Citations

Evaluating the significance of a paper is pivotal yet challenging for the scientific community. While the citation count is the most commonly used proxy for this purpose, they are widely criticized for failing to accurately reflect a paper's true impact. In this work, we propose a causal inference method, TextMatch, which adapts the traditional matching framework to high-dimensional text embeddings. Specifically, we encode each paper using the text embeddings by large language models (LLMs), extract similar samples by cosine similarity, and synthesize a counterfactual sample by the weighted average of similar papers according to their similarity values. We apply the resulting metric, called CausalCite, as a causal formulation of paper citations. We show its effectiveness on various criteria, such as high correlation with paper impact as reported by scientific experts on a previous dataset of 1K papers, (test-of-time) awards for past papers, and its stability across various sub-fields of AI. We also provide a set of findings that can serve as suggested ways for future researchers to use our metric for a better understanding of a paper's quality. Our code and data are at https://github.com/causalNLP/causal-cite.

Learning Generalizable Agents via Saliency-Guided Features Decorrelation

In visual-based Reinforcement Learning (RL), agents often struggle to generalize well to environmental variations in the state space that were not observed during training. The variations can arise in both task-irrelevant features, such as background noise, and task-relevant features, such as robot configurations, that are related to the optimal decisions. To achieve generalization in both situations, agents are required to accurately understand the impact of changed features on the decisions, i.e., establishing the true associations between changed features and decisions in the policy model. However, due to the inherent correlations among features in the state space, the associations between features and decisions become entangled, making it difficult for the policy to distinguish them. To this end, we propose Saliency-Guided Features Decorrelation (SGFD) to eliminate these correlations through sample reweighting. Concretely, SGFD consists of two core techniques: Random Fourier Functions (RFF) and the saliency map. RFF is utilized to estimate the complex non-linear correlations in high-dimensional images, while the saliency map is designed to identify the changed features. Under the guidance of the saliency map, SGFD employs sample reweighting to minimize the estimated correlations related to changed features, thereby achieving decorrelation in visual RL tasks. Our experimental results demonstrate that SGFD can generalize well on a wide range of test environments and significantly outperforms state-of-the-art methods in handling both task-irrelevant variations and task-relevant variations.

Diffusing on Two Levels and Optimizing for Multiple Properties: A Novel Approach to Generating Molecules with Desirable Properties

In the past decade, Artificial Intelligence driven drug design and discovery has been a hot research topic, where an important branch is molecule generation by generative models, from GAN-based models and VAE-based models to the latest diffusion-based models. However, most existing models pursue only the basic properties like validity and uniqueness of the generated molecules, a few go further to explicitly optimize one single important molecular property (e.g. QED or PlogP), which makes most generated molecules little usefulness in practice. In this paper, we present a novel approach to generating molecules with desirable properties, which expands the diffusion model framework with multiple innovative designs. The novelty is two-fold. On the one hand, considering that the structures of molecules are complex and diverse, and molecular properties are usually determined by some substructures (e.g. pharmacophores), we propose to perform diffusion on two structural levels: molecules and molecular fragments respectively, with which a mixed Gaussian distribution is obtained for the reverse diffusion process. To get desirable molecular fragments, we develop a novel electronic effect based fragmentation method. On the other hand, we introduce two ways to explicitly optimize multiple molecular properties under the diffusion model framework. First, as potential drug molecules must be chemically valid, we optimize molecular validity by an energy-guidance function. Second, since potential drug molecules should be desirable in various properties, we employ a multi-objective mechanism to optimize multiple molecular properties simultaneously. Extensive experiments with two benchmark datasets QM9 and ZINC250k show that the molecules generated by our proposed method have better validity, uniqueness, novelty, Fr\'echet ChemNet Distance (FCD), QED, and PlogP than those generated by current SOTA models.

A Simple Unified Uncertainty-Guided Framework for Offline-to-Online Reinforcement Learning

Offline reinforcement learning (RL) provides a promising solution to learning an agent fully relying on a data-driven paradigm. However, constrained by the limited quality of the offline dataset, its performance is often sub-optimal. Therefore, it is desired to further finetune the agent via extra online interactions before deployment. Unfortunately, offline-to-online RL can be challenging due to two main challenges: constrained exploratory behavior and state-action distribution shift. To this end, we propose a Simple Unified uNcertainty-Guided (SUNG) framework, which naturally unifies the solution to both challenges with the tool of uncertainty. Specifically, SUNG quantifies uncertainty via a VAE-based state-action visitation density estimator. To facilitate efficient exploration, SUNG presents a practical optimistic exploration strategy to select informative actions with both high value and high uncertainty. Moreover, SUNG develops an adaptive exploitation method by applying conservative offline RL objectives to high-uncertainty samples and standard online RL objectives to low-uncertainty samples to smoothly bridge offline and online stages. SUNG achieves state-of-the-art online finetuning performance when combined with different offline RL methods, across various environments and datasets in D4RL benchmark.