3D molecule generation is crucial for drug discovery and material design. While prior efforts focus on 3D diffusion models for their benefits in modeling continuous 3D conformers, they overlook the advantages of 1D SELFIES-based Language Models (LMs), which can generate 100% valid molecules and leverage the billion-scale 1D molecule datasets. To combine these advantages for 3D molecule generation, we propose a foundation model -- NExT-Mol: 3D Diffusion Meets 1D Language Modeling for 3D Molecule Generation. NExT-Mol uses an extensively pretrained molecule LM for 1D molecule generation, and subsequently predicts the generated molecule's 3D conformers with a 3D diffusion model. We enhance NExT-Mol's performance by scaling up the LM's model size, refining the diffusion neural architecture, and applying 1D to 3D transfer learning. Notably, our 1D molecule LM significantly outperforms baselines in distributional similarity while ensuring validity, and our 3D diffusion model achieves leading performances in conformer prediction. Given these improvements in 1D and 3D modeling, NExT-Mol achieves a 26% relative improvement in 3D FCD for de novo 3D generation on GEOM-DRUGS, and a 13% average relative gain for conditional 3D generation on QM9-2014. Our codes and pretrained checkpoints are available at https://github.com/acharkq/NExT-Mol.

Molecule-text modeling, which aims to facilitate molecule-relevant tasks with a textual interface and textual knowledge, is an emerging research direction. Beyond single molecules, studying reaction-text modeling holds promise for helping the synthesis of new materials and drugs. However, previous works mostly neglect reaction-text modeling: they primarily focus on modeling individual molecule-text pairs or learning chemical reactions without texts in context. Additionally, one key task of reaction-text modeling -- experimental procedure prediction -- is less explored due to the absence of an open-source dataset. The task is to predict step-by-step actions of conducting chemical experiments and is crucial to automating chemical synthesis. To resolve the challenges above, we propose a new pretraining method, ReactXT, for reaction-text modeling, and a new dataset, OpenExp, for experimental procedure prediction. Specifically, ReactXT features three types of input contexts to incrementally pretrain LMs. Each of the three input contexts corresponds to a pretraining task to improve the text-based understanding of either reactions or single molecules. ReactXT demonstrates consistent improvements in experimental procedure prediction and molecule captioning and offers competitive results in retrosynthesis. Our code is available at https://github.com/syr-cn/ReactXT.

Language Models (LMs) excel in understanding textual descriptions of proteins, as evident in biomedical question-answering tasks. However, their capability falters with raw protein data, such as amino acid sequences, due to a deficit in pretraining on such data. Conversely, Protein Language Models (PLMs) can understand and convert protein data into high-quality representations, but struggle to process texts. To address their limitations, we introduce ProtT3, a framework for Protein-to-Text Generation for Text-based Protein Understanding. ProtT3 empowers an LM to understand protein sequences of amino acids by incorporating a PLM as its protein understanding module, enabling effective protein-to-text generation. This collaboration between PLM and LM is facilitated by a cross-modal projector (i.e., Q-Former) that bridges the modality gap between the PLM's representation space and the LM's input space. Unlike previous studies focusing on protein property prediction and protein-text retrieval, we delve into the largely unexplored field of protein-to-text generation. To facilitate comprehensive benchmarks and promote future research, we establish quantitative evaluations for protein-text modeling tasks, including protein captioning, protein question-answering, and protein-text retrieval. Our experiments show that ProtT3 substantially surpasses current baselines, with ablation studies further highlighting the efficacy of its core components. Our code is available at https://github.com/acharkq/ProtT3.

Attention-based models are proliferating in the space of image analytics, including segmentation. The standard method of feeding images to transformer encoders is to divide the images into patches and then feed the patches to the model as a linear sequence of tokens. For high-resolution images, e.g. microscopic pathology images, the quadratic compute and memory cost prohibits the use of an attention-based model, if we are to use smaller patch sizes that are favorable in segmentation. The solution is to either use custom complex multi-resolution models or approximate attention schemes. We take inspiration from Adapative Mesh Refinement (AMR) methods in HPC by adaptively patching the images, as a pre-processing step, based on the image details to reduce the number of patches being fed to the model, by orders of magnitude. This method has a negligible overhead, and works seamlessly with any attention-based model, i.e. it is a pre-processing step that can be adopted by any attention-based model without friction. We demonstrate superior segmentation quality over SoTA segmentation models for real-world pathology datasets while gaining a geomean speedup of $6.9\times$ for resolutions up to $64K^2$, on up to $2,048$ GPUs.

Scrutinizing previous studies, we can reveal a common scheme consisting of three key components: (1) graph tokenizer, which breaks a molecular graph into smaller fragments (i.e., subgraphs) and converts them into tokens; (2) graph masking, which corrupts the graph with masks; (3) graph autoencoder, which first applies an encoder on the masked graph to generate the representations, and then employs a decoder on the representations to recover the tokens of the original graph. However, the previous MGM studies focus extensively on graph masking and encoder, while there is limited understanding of tokenizer and decoder. To bridge the gap, we first summarize popular molecule tokenizers at the granularity of node, edge, motif, and Graph Neural Networks (GNNs), and then examine their roles as the MGM's reconstruction targets. Further, we explore the potential of adopting an expressive decoder in MGM. Our results show that a subgraph-level tokenizer and a sufficiently expressive decoder with remask decoding have a large impact on the encoder's representation learning. Finally, we propose a novel MGM method SimSGT, featuring a Simple GNN-based Tokenizer (SGT) and an effective decoding strategy. We empirically validate that our method outperforms the existing molecule self-supervised learning methods. Our codes and checkpoints are available at https://github.com/syr-cn/SimSGT.

Predicting chemical reactions, a fundamental challenge in chemistry, involves forecasting the resulting products from a given reaction process. Conventional techniques, notably those employing Graph Neural Networks (GNNs), are often limited by insufficient training data and their inability to utilize textual information, undermining their applicability in real-world applications. In this work, we propose ReLM, a novel framework that leverages the chemical knowledge encoded in language models (LMs) to assist GNNs, thereby enhancing the accuracy of real-world chemical reaction predictions. To further enhance the model's robustness and interpretability, we incorporate the confidence score strategy, enabling the LMs to self-assess the reliability of their predictions. Our experimental results demonstrate that ReLM improves the performance of state-of-the-art GNN-based methods across various chemical reaction datasets, especially in out-of-distribution settings. Codes are available at https://github.com/syr-cn/ReLM.