Physical formula enhanced multi-task learning for pharmacokinetics prediction

Artificial intelligence (AI) technology has demonstrated remarkable potential in drug dis-covery, where pharmacokinetics plays a crucial role in determining the dosage, safety, and efficacy of new drugs. A major challenge for AI-driven drug discovery (AIDD) is the scarcity of high-quality data, which often requires extensive wet-lab work. A typical example of this is pharmacokinetic experiments. In this work, we develop a physical formula enhanced mul-ti-task learning (PEMAL) method that predicts four key parameters of pharmacokinetics simultaneously. By incorporating physical formulas into the multi-task framework, PEMAL facilitates effective knowledge sharing and target alignment among the pharmacokinetic parameters, thereby enhancing the accuracy of prediction. Our experiments reveal that PEMAL significantly lowers the data demand, compared to typical Graph Neural Networks. Moreover, we demonstrate that PEMAL enhances the robustness to noise, an advantage that conventional Neural Networks do not possess. Another advantage of PEMAL is its high flexibility, which can be potentially applied to other multi-task machine learning scenarios. Overall, our work illustrates the benefits and potential of using PEMAL in AIDD and other scenarios with data scarcity and noise.

Large Language Models are In-Context Molecule Learners

Large Language Models (LLMs) have demonstrated exceptional performance in biochemical tasks, especially the molecule caption translation task, which aims to bridge the gap between molecules and natural language texts. However, previous methods in adapting LLMs to the molecule-caption translation task required extra domain-specific pre-training stages, suffered weak alignment between molecular and textual spaces, or imposed stringent demands on the scale of LLMs. To resolve the challenges, we propose In-Context Molecule Adaptation (ICMA), as a new paradigm allowing LLMs to learn the molecule-text alignment from context examples via In-Context Molecule Tuning. Specifically, ICMA incorporates the following three stages: Cross-modal Retrieval, Post-retrieval Re-ranking, and In-context Molecule Tuning. Initially, Cross-modal Retrieval utilizes BM25 Caption Retrieval and Molecule Graph Retrieval to retrieve informative context examples. Additionally, we also propose Post-retrieval Re-ranking with Sequence Reversal and Random Walk to further improve the quality of retrieval results. Finally, In-Context Molecule Tuning unlocks the in-context molecule learning capability of LLMs with retrieved examples and adapts the parameters of LLMs for the molecule-caption translation task. Experimental results demonstrate that ICMT can empower LLMs to achieve state-of-the-art or comparable performance without extra training corpora and intricate structures, showing that LLMs are inherently in-context molecule learners.

ChemLLM: A Chemical Large Language Model

Large language models (LLMs) have made impressive progress in chemistry applications, including molecular property prediction, molecular generation, experimental protocol design, etc. However, the community lacks a dialogue-based model specifically designed for chemistry. The challenge arises from the fact that most chemical data and scientific knowledge are primarily stored in structured databases, and the direct use of these structured data compromises the model's ability to maintain coherent dialogue. To tackle this issue, we develop a novel template-based instruction construction method that transforms structured knowledge into plain dialogue, making it suitable for language model training. By leveraging this approach, we develop ChemLLM, the first large language model dedicated to chemistry, capable of performing various tasks across chemical disciplines with smooth dialogue interaction. ChemLLM beats GPT-3.5 on all three principal tasks in chemistry, i.e., name conversion, molecular caption, and reaction prediction, and surpasses GPT-4 on two of them. Remarkably, ChemLLM also shows exceptional adaptability to related mathematical and physical tasks despite being trained mainly on chemical-centric corpora. Furthermore, ChemLLM demonstrates proficiency in specialized NLP tasks within chemistry, such as literature translation and cheminformatic programming. ChemLLM opens up a new avenue for exploration within chemical studies, while our method of integrating structured chemical knowledge into dialogue systems sets a new frontier for developing LLMs across various scientific fields. Codes, Datasets, and Model weights are publicly accessible at hf.co/AI4Chem/ChemLLM-7B-Chat.

An Comparative Analysis of Different Pitch and Metrical Grid Encoding Methods in the Task of Sequential Music Generation

Pitch and meter are two fundamental music features for symbolic music generation tasks, where researchers usually choose different encoding methods depending on specific goals. However, the advantages and drawbacks of different encoding methods have not been frequently discussed. This paper presents a integrated analysis of the influence of two low-level feature, pitch and meter, on the performance of a token-based sequential music generation model. First, the commonly used MIDI number encoding and a less used class-octave encoding are compared. Second, an dense intra-bar metric grid is imposed to the encoded sequence as auxiliary features. Different complexity and resolutions of the metric grid are compared. For complexity, the single token approach and the multiple token approach are compared; for grid resolution, 0 (ablation), 1 (bar-level), 4 (downbeat-level) 12, (8th-triplet-level) up to 64 (64th-note-grid-level) are compared; for duration resolution, 4, 8, 12 and 16 subdivisions per beat are compared. All different encodings are tested on separately trained Transformer-XL models for a melody generation task. Regarding distribution similarity of several objective evaluation metrics to the test dataset, results suggest that the class-octave encoding significantly outperforms the taken-for-granted MIDI encoding on pitch-related metrics; finer grids and multiple-token grids improve the rhythmic quality, but also suffer from over-fitting at early training stage. Results display a general phenomenon of over-fitting from two aspects, the pitch embedding space and the test loss of the single-token grid encoding. From a practical perspective, we both demonstrate the feasibility and raise the concern of easy over-fitting problem of using smaller networks and lower embedding dimensions on the generation task. The findings can also contribute to futural models in terms of feature engineering.

Minimax Weight Learning for Absorbing MDPs

Reinforcement learning policy evaluation problems are often modeled as finite or discounted/averaged infinite-horizon MDPs. In this paper, we study undiscounted off-policy policy evaluation for absorbing MDPs. Given the dataset consisting of the i.i.d episodes with a given truncation level, we propose a so-called MWLA algorithm to directly estimate the expected return via the importance ratio of the state-action occupancy measure. The Mean Square Error (MSE) bound for the MWLA method is investigated and the dependence of statistical errors on the data size and the truncation level are analyzed. With an episodic taxi environment, computational experiments illustrate the performance of the MWLA algorithm.