Gibbs Max-margin Topic Models with Data Augmentation

Max-margin learning is a powerful approach to building classifiers and structured output predictors. Recent work on max-margin supervised topic models has successfully integrated it with Bayesian topic models to discover discriminative latent semantic structures and make accurate predictions for unseen testing data. However, the resulting learning problems are usually hard to solve because of the non-smoothness of the margin loss. Existing approaches to building max-margin supervised topic models rely on an iterative procedure to solve multiple latent SVM subproblems with additional mean-field assumptions on the desired posterior distributions. This paper presents an alternative approach by defining a new max-margin loss. Namely, we present Gibbs max-margin supervised topic models, a latent variable Gibbs classifier to discover hidden topic representations for various tasks, including classification, regression and multi-task learning. Gibbs max-margin supervised topic models minimize an expected margin loss, which is an upper bound of the existing margin loss derived from an expected prediction rule. By introducing augmented variables and integrating out the Dirichlet variables analytically by conjugacy, we develop simple Gibbs sampling algorithms with no restricting assumptions and no need to solve SVM subproblems. Furthermore, each step of the "augment-and-collapse" Gibbs sampling algorithms has an analytical conditional distribution, from which samples can be easily drawn. Experimental results demonstrate significant improvements on time efficiency. The classification performance is also significantly improved over competitors on binary, multi-class and multi-label classification tasks.Comment: 35 page

Unsupervisedly Prompting AlphaFold2 for Few-Shot Learning of Accurate Folding Landscape and Protein Structure Prediction

Data-driven predictive methods which can efficiently and accurately transform protein sequences into biologically active structures are highly valuable for scientific research and medical development. Determining accurate folding landscape using co-evolutionary information is fundamental to the success of modern protein structure prediction methods. As the state of the art, AlphaFold2 has dramatically raised the accuracy without performing explicit co-evolutionary analysis. Nevertheless, its performance still shows strong dependence on available sequence homologs. Based on the interrogation on the cause of such dependence, we presented EvoGen, a meta generative model, to remedy the underperformance of AlphaFold2 for poor MSA targets. By prompting the model with calibrated or virtually generated homologue sequences, EvoGen helps AlphaFold2 fold accurately in low-data regime and even achieve encouraging performance with single-sequence predictions. Being able to make accurate predictions with few-shot MSA not only generalizes AlphaFold2 better for orphan sequences, but also democratizes its use for high-throughput applications. Besides, EvoGen combined with AlphaFold2 yields a probabilistic structure generation method which could explore alternative conformations of protein sequences, and the task-aware differentiable algorithm for sequence generation will benefit other related tasks including protein design.Comment: version 2.0; 28 pages, 6 figure

Towards Data-centric Graph Machine Learning: Review and Outlook

Data-centric AI, with its primary focus on the collection, management, and utilization of data to drive AI models and applications, has attracted increasing attention in recent years. In this article, we conduct an in-depth and comprehensive review, offering a forward-looking outlook on the current efforts in data-centric AI pertaining to graph data-the fundamental data structure for representing and capturing intricate dependencies among massive and diverse real-life entities. We introduce a systematic framework, Data-centric Graph Machine Learning (DC-GML), that encompasses all stages of the graph data lifecycle, including graph data collection, exploration, improvement, exploitation, and maintenance. A thorough taxonomy of each stage is presented to answer three critical graph-centric questions: (1) how to enhance graph data availability and quality; (2) how to learn from graph data with limited-availability and low-quality; (3) how to build graph MLOps systems from the graph data-centric view. Lastly, we pinpoint the future prospects of the DC-GML domain, providing insights to navigate its advancements and applications.Comment: 42 pages, 9 figure

Retrosynthesis prediction enhanced by in-silico reaction data augmentation

Recent advances in machine learning (ML) have expedited retrosynthesis research by assisting chemists to design experiments more efficiently. However, all ML-based methods consume substantial amounts of paired training data (i.e., chemical reaction: product-reactant(s) pair), which is costly to obtain. Moreover, companies view reaction data as a valuable asset and restrict the accessibility to researchers. These issues prevent the creation of more powerful retrosynthesis models due to their data-driven nature. As a response, we exploit easy-to-access unpaired data (i.e., one component of product-reactant(s) pair) for generating in-silico paired data to facilitate model training. Specifically, we present RetroWISE, a self-boosting framework that employs a base model inferred from real paired data to perform in-silico reaction generation and augmentation using unpaired data, ultimately leading to a superior model. On three benchmark datasets, RetroWISE achieves the best overall performance against state-of-the-art models (e.g., +8.6% top-1 accuracy on the USPTO-50K test dataset). Moreover, it consistently improves the prediction accuracy of rare transformations. These results show that Retro- WISE overcomes the training bottleneck by in-silico reactions, thereby paving the way toward more effective ML-based retrosynthesis models

Protein-Ligand Scoring with Convolutional Neural Networks

Computational approaches to drug discovery can reduce the time and cost associated with experimental assays and enable the screening of novel chemotypes. Structure-based drug design methods rely on scoring functions to rank and predict binding affinities and poses. The ever-expanding amount of protein-ligand binding and structural data enables the use of deep machine learning techniques for protein-ligand scoring. We describe convolutional neural network (CNN) scoring functions that take as input a comprehensive 3D representation of a protein-ligand interaction. A CNN scoring function automatically learns the key features of protein-ligand interactions that correlate with binding. We train and optimize our CNN scoring functions to discriminate between correct and incorrect binding poses and known binders and non-binders. We find that our CNN scoring function outperforms the AutoDock Vina scoring function when ranking poses both for pose prediction and virtual screening

Generative Augmented Flow Networks

The Generative Flow Network is a probabilistic framework where an agent learns a stochastic policy for object generation, such that the probability of generating an object is proportional to a given reward function. Its effectiveness has been shown in discovering high-quality and diverse solutions, compared to reward-maximizing reinforcement learning-based methods. Nonetheless, GFlowNets only learn from rewards of the terminal states, which can limit its applicability. Indeed, intermediate rewards play a critical role in learning, for example from intrinsic motivation to provide intermediate feedback even in particularly challenging sparse reward tasks. Inspired by this, we propose Generative Augmented Flow Networks (GAFlowNets), a novel learning framework to incorporate intermediate rewards into GFlowNets. We specify intermediate rewards by intrinsic motivation to tackle the exploration problem in sparse reward environments. GAFlowNets can leverage edge-based and state-based intrinsic rewards in a joint way to improve exploration. Based on extensive experiments on the GridWorld task, we demonstrate the effectiveness and efficiency of GAFlowNet in terms of convergence, performance, and diversity of solutions. We further show that GAFlowNet is scalable to a more complex and large-scale molecule generation domain, where it achieves consistent and significant performance improvement