Lin Yao

Shuqi Lu, Lin Yao, Xi Chen et al. · microsoft-research

Structure-based drug design, i.e., finding molecules with high affinities to the target protein pocket, is one of the most critical tasks in drug discovery. Traditional solutions, like virtual screening, require exhaustively searching on a large molecular database, which are inefficient and cannot return novel molecules beyond the database. The pocket-based 3D molecular generation model, i.e., directly generating a molecule with a 3D structure and binding position in the pocket, is a new promising way to address this issue. Herein, we propose VD-Gen, a novel pocket-based 3D molecular generation pipeline. VD-Gen consists of several carefully designed stages to generate fine-grained 3D molecules with binding positions in the pocket cavity end-to-end. Rather than directly generating or sampling atoms with 3D positions in the pocket like in early attempts, in VD-Gen, we first randomly initialize many virtual particles in the pocket; then iteratively move these virtual particles, making the distribution of virtual particles approximate the distribution of molecular atoms. After virtual particles are stabilized in 3D space, we extract a 3D molecule from them. Finally, we further refine atoms in the extracted molecule by iterative movement again, to get a high-quality 3D molecule, and predict a confidence score for it. Extensive experiment results on pocket-based molecular generation demonstrate that VD-Gen can generate novel 3D molecules to fill the target pocket cavity with high binding affinities, significantly outperforming previous baselines.

Chunyu Xie, Heng Cai, Jincheng Li et al.

Vision-language pre-training (VLP) on large-scale datasets has shown premier performance on various downstream tasks. In contrast to plenty of available benchmarks with English corpus, large-scale pre-training datasets and downstream datasets with Chinese corpus remain largely unexplored. In this work, we build a large-scale high-quality Chinese Cross-Modal Benchmark named CCMB for the research community, which contains the currently largest public pre-training dataset Zero and five human-annotated fine-tuning datasets for downstream tasks. Zero contains 250 million images paired with 750 million text descriptions, plus two of the five fine-tuning datasets are also currently the largest ones for Chinese cross-modal downstream tasks. Along with the CCMB, we also develop a VLP framework named R2D2, applying a pre-Ranking + Ranking strategy to learn powerful vision-language representations and a two-way distillation method (i.e., target-guided Distillation and feature-guided Distillation) to further enhance the learning capability. With the Zero and the R2D2 VLP framework, we achieve state-of-the-art performance on twelve downstream datasets from five broad categories of tasks including image-text retrieval, image-text matching, image caption, text-to-image generation, and zero-shot image classification. The datasets, models, and codes are available at https://github.com/yuxie11/R2D2

Lin Yao, Ruihan Xu, Zhifeng Gao et al. · microsoft-research

The central problem in cryo-electron microscopy (cryo-EM) is to recover the 3D structure from noisy 2D projection images which requires estimating the missing projection angles (poses). Recent methods attempted to solve the 3D reconstruction problem with the autoencoder architecture, which suffers from the latent vector space sampling problem and frequently produces suboptimal pose inferences and inferior 3D reconstructions. Here we present an improved autoencoder architecture called ACE (Asymmetric Complementary autoEncoder), based on which we designed the ACE-EM method for cryo-EM 3D reconstructions. Compared to previous methods, ACE-EM reached higher pose space coverage within the same training time and boosted the reconstruction performance regardless of the choice of decoders. With this method, the Nyquist resolution (highest possible resolution) was reached for 3D reconstructions of both simulated and experimental cryo-EM datasets. Furthermore, ACE-EM is the only amortized inference method that reached the Nyquist resolution.

Lin Yao, Wentao Guo, Zhen Wang et al.

Single-step retrosynthesis (SSR) in organic chemistry is increasingly benefiting from deep learning (DL) techniques in computer-aided synthesis design. While template-free DL models are flexible and promising for retrosynthesis prediction, they often ignore vital 2D molecular information and struggle with atom alignment for node generation, resulting in lower performance compared to the template-based and semi-template-based methods. To address these issues, we introduce Node-Aligned Graph-to-Graph (NAG2G), a transformer-based template-free DL model. NAG2G combines 2D molecular graphs and 3D conformations to retain comprehensive molecular details and incorporates product-reactant atom mapping through node alignment which determines the order of the node-by-node graph outputs process in an auto-regressive manner. Through rigorous benchmarking and detailed case studies, we have demonstrated that NAG2G stands out with its remarkable predictive accuracy on the expansive datasets of USPTO-50k and USPTO-FULL. Moreover, the model's practical utility is underscored by its successful prediction of synthesis pathways for multiple drug candidate molecules. This not only proves NAG2G's robustness but also its potential to revolutionize the prediction of complex chemical synthesis processes for future synthetic route design tasks.

Shang Xiang, Lin Yao, Zhen Wang et al.

The field of computer-aided synthesis planning (CASP) has seen rapid advancements in recent years, achieving significant progress across various algorithmic benchmarks. However, chemists often encounter numerous infeasible reactions when using CASP in practice. This article delves into common errors associated with CASP and introduces a product prediction model aimed at enhancing the accuracy of single-step models. While the product prediction model reduces the number of single-step reactions, it integrates multiple single-step models to maintain the overall reaction count and increase reaction diversity. Based on manual analysis and large-scale testing, the product prediction model, combined with the multi-model ensemble approach, has been proven to offer higher feasibility and greater diversity.

Lin Yao, Jianfei Song, Ruizhuo Xu et al.

Historically lower-level tasks such as automatic speech recognition (ASR) and speaker identification are the main focus in the speech field. Interest has been growing in higher-level spoken language understanding (SLU) tasks recently, like sentiment analysis (SA). However, improving performances on SLU tasks remains a big challenge. Basically, there are two main methods for SLU tasks: (1) Two-stage method, which uses a speech model to transfer speech to text, then uses a language model to get the results of downstream tasks; (2) One-stage method, which just fine-tunes a pre-trained speech model to fit in the downstream tasks. The first method loses emotional cues such as intonation, and causes recognition errors during ASR process, and the second one lacks necessary language knowledge. In this paper, we propose the Wave BERT (WaBERT), a novel end-to-end model combining the speech model and the language model for SLU tasks. WaBERT is based on the pre-trained speech and language model, hence training from scratch is not needed. We also set most parameters of WaBERT frozen during training. By introducing WaBERT, audio-specific information and language knowledge are integrated in the short-time and low-resource training process to improve results on the dev dataset of SLUE SA tasks by 1.15% of recall score and 0.82% of F1 score. Additionally, we modify the serial Continuous Integrate-and-Fire (CIF) mechanism to achieve the monotonic alignment between the speech and text modalities.

Qingsi Lai, Fanjie Xu, Lin Yao et al.

Powder X-ray diffraction (PXRD) is a prevalent technique in materials characterization. While the analysis of PXRD often requires extensive human manual intervention, and most automated method only achieved at coarse-grained level. The more difficult and important task of fine-grained crystal structure prediction from PXRD remains unaddressed. This study introduces XtalNet, the first equivariant deep generative model for end-to-end crystal structure prediction from PXRD. Unlike previous crystal structure prediction methods that rely solely on composition, XtalNet leverages PXRD as an additional condition, eliminating ambiguity and enabling the generation of complex organic structures with up to 400 atoms in the unit cell. XtalNet comprises two modules: a Contrastive PXRD-Crystal Pretraining (CPCP) module that aligns PXRD space with crystal structure space, and a Conditional Crystal Structure Generation (CCSG) module that generates candidate crystal structures conditioned on PXRD patterns. Evaluation on two MOF datasets (hMOF-100 and hMOF-400) demonstrates XtalNet's effectiveness. XtalNet achieves a top-10 Match Rate of 90.2% and 79% for hMOF-100 and hMOF-400 in conditional crystal structure prediction task, respectively. XtalNet enables the direct prediction of crystal structures from experimental measurements, eliminating the need for manual intervention and external databases. This opens up new possibilities for automated crystal structure determination and the accelerated discovery of novel materials.

Lin Yao, Da Yang, James P. C. Duncan et al.

The Madden-Julian oscillation (MJO) is a planetary-scale, intraseasonal tropical rainfall phenomenon crucial for global weather and climate; however, its dynamics and predictability remain poorly understood. Here, we leverage deep learning (DL) to investigate the sources of MJO predictability, motivated by a central difference in MJO theories: which spatial scales are essential for driving the MJO? We first develop a deep convolutional neural network (DCNN) to forecast the MJO indices (RMM and ROMI). Our model predicts RMM and ROMI up to 21 and 33 days, respectively, achieving skills comparable to leading subseasonal-to-seasonal models such as NCEP. To identify the spatial scales most relevant for MJO forecasting, we conduct spectral analysis of the latent feature space and find that large-scale patterns dominate the learned signals. Additional experiments show that models using only large-scale signals as the input have the same skills as those using all the scales, supporting the large-scale view of the MJO. Meanwhile, we find that small-scale signals remain informative: surprisingly, models using only small-scale input can still produce skillful forecasts up to 1-2 weeks ahead. We show that this is achieved by reconstructing the large-scale envelope of the small-scale activities, which aligns with the multi-scale view of the MJO. Altogether, our findings support that large-scale patterns--whether directly included or reconstructed--may be the primary source of MJO predictability.