Hongyu Guo

Shengchao Liu, Jiongxiao Wang, Yijin Yang et al.

Recent advancements in conversational large language models (LLMs), such as ChatGPT, have demonstrated remarkable promise in various domains, including drug discovery. However, existing works mainly focus on investigating the capabilities of conversational LLMs on chemical reaction and retrosynthesis. While drug editing, a critical task in the drug discovery pipeline, remains largely unexplored. To bridge this gap, we propose ChatDrug, a framework to facilitate the systematic investigation of drug editing using LLMs. ChatDrug jointly leverages a prompt module, a retrieval and domain feedback (ReDF) module, and a conversation module to streamline effective drug editing. We empirically show that ChatDrug reaches the best performance on 33 out of 39 drug editing tasks, encompassing small molecules, peptides, and proteins. We further demonstrate, through 10 case studies, that ChatDrug can successfully identify the key substructures (e.g., the molecule functional groups, peptide motifs, and protein structures) for manipulation, generating diverse and valid suggestions for drug editing. Promisingly, we also show that ChatDrug can offer insightful explanations from a domain-specific perspective, enhancing interpretability and enabling informed decision-making. This research sheds light on the potential of ChatGPT and conversational LLMs for drug editing. It paves the way for a more efficient and collaborative drug discovery pipeline, contributing to the advancement of pharmaceutical research and development.

Shengchao Liu, Weitao Du, Zhiming Ma et al.

Molecule pretraining has quickly become the go-to schema to boost the performance of AI-based drug discovery. Naturally, molecules can be represented as 2D topological graphs or 3D geometric point clouds. Although most existing pertaining methods focus on merely the single modality, recent research has shown that maximizing the mutual information (MI) between such two modalities enhances the molecule representation ability. Meanwhile, existing molecule multi-modal pretraining approaches approximate MI based on the representation space encoded from the topology and geometry, thus resulting in the loss of critical structural information of molecules. To address this issue, we propose MoleculeSDE. MoleculeSDE leverages group symmetric (e.g., SE(3)-equivariant and reflection-antisymmetric) stochastic differential equation models to generate the 3D geometries from 2D topologies, and vice versa, directly in the input space. It not only obtains tighter MI bound but also enables prosperous downstream tasks than the previous work. By comparing with 17 pretraining baselines, we empirically verify that MoleculeSDE can learn an expressive representation with state-of-the-art performance on 26 out of 32 downstream tasks.

Hongyu Guo

Label Smoothing (LS) improves model generalization through penalizing models from generating overconfident output distributions. For each training sample the LS strategy smooths the one-hot encoded training signal by distributing its distribution mass over the non-ground truth classes. We extend this technique by considering example pairs, coined PLS. PLS first creates midpoint samples by averaging random sample pairs and then learns a smoothing distribution during training for each of these midpoint samples, resulting in midpoints with high uncertainty labels for training. We empirically show that PLS significantly outperforms LS, achieving up to 30% of relative classification error reduction. We also visualize that PLS produces very low winning softmax scores for both in and out of distribution samples.

Hangrui Bi, Hengyi Wang, Chence Shi et al.

Reliably predicting the products of chemical reactions presents a fundamental challenge in synthetic chemistry. Existing machine learning approaches typically produce a reaction product by sequentially forming its subparts or intermediate molecules. Such autoregressive methods, however, not only require a pre-defined order for the incremental construction but preclude the use of parallel decoding for efficient computation. To address these issues, we devise a non-autoregressive learning paradigm that predicts reaction in one shot. Leveraging the fact that chemical reactions can be described as a redistribution of electrons in molecules, we formulate a reaction as an arbitrary electron flow and predict it with a novel multi-pointer decoding network. Experiments on the USPTO-MIT dataset show that our approach has established a new state-of-the-art top-1 accuracy and achieves at least 27 times inference speedup over the state-of-the-art methods. Also, our predictions are easier for chemists to interpret owing to predicting the electron flows.

Hongyu Guo, Khalique Newaz, Scott Emrich et al.

As proteins with similar structures often have similar functions, analysis of protein structures can help predict protein functions and is thus important. We consider the problem of protein structure classification, which computationally classifies the structures of proteins into pre-defined groups. We develop a weighted network that depicts the protein structures, and more importantly, we propose the first graphlet-based measure that applies to weighted networks. Further, we develop a deep neural network (DNN) composed of both convolutional and recurrent layers to use this measure for classification. Put together, our approach shows dramatic improvements in performance over existing graphlet-based approaches on 36 real datasets. Even comparing with the state-of-the-art approach, it almost halves the classification error. In addition to protein structure networks, our weighted-graphlet measure and DNN classifier can potentially be applied to classification of other weighted networks in computational biology as well as in other domains.

Hongyu Guo, Yongyi Mao, Ali Al-Bashabsheh et al.

Based on the notion of information bottleneck (IB), we formulate a quantization problem called "IB quantization". We show that IB quantization is equivalent to learning based on the IB principle. Under this equivalence, the standard neural network models can be viewed as scalar (single sample) IB quantizers. It is known, from conventional rate-distortion theory, that scalar quantizers are inferior to vector (multi-sample) quantizers. Such a deficiency then inspires us to develop a novel learning framework, AgrLearn, that corresponds to vector IB quantizers for learning with neural networks. Unlike standard networks, AgrLearn simultaneously optimizes against multiple data samples. We experimentally verify that AgrLearn can result in significant improvements when applied to several current deep learning architectures for image recognition and text classification. We also empirically show that AgrLearn can reduce up to 80% of the training samples needed for ResNet training.

Martin Renqiang Min, Hongyu Guo, Dongjin Song

Metric learning methods for dimensionality reduction in combination with k-Nearest Neighbors (kNN) have been extensively deployed in many classification, data embedding, and information retrieval applications. However, most of these approaches involve pairwise training data comparisons, and thus have quadratic computational complexity with respect to the size of training set, preventing them from scaling to fairly big datasets. Moreover, during testing, comparing test data against all the training data points is also expensive in terms of both computational cost and resources required. Furthermore, previous metrics are either too constrained or too expressive to be well learned. To effectively solve these issues, we present an exemplar-centered supervised shallow parametric data embedding model, using a Maximally Collapsing Metric Learning (MCML) objective. Our strategy learns a shallow high-order parametric embedding function and compares training/test data only with learned or precomputed exemplars, resulting in a cost function with linear computational complexity for both training and testing. We also empirically demonstrate, using several benchmark datasets, that for classification in two-dimensional embedding space, our approach not only gains speedup of kNN by hundreds of times, but also outperforms state-of-the-art supervised embedding approaches.

Hongyu Guo

We introduce a novel schema for sequence to sequence learning with a Deep Q-Network (DQN), which decodes the output sequence iteratively. The aim here is to enable the decoder to first tackle easier portions of the sequences, and then turn to cope with difficult parts. Specifically, in each iteration, an encoder-decoder Long Short-Term Memory (LSTM) network is employed to, from the input sequence, automatically create features to represent the internal states of and formulate a list of potential actions for the DQN. Take rephrasing a natural sentence as an example. This list can contain ranked potential words. Next, the DQN learns to make decision on which action (e.g., word) will be selected from the list to modify the current decoded sequence. The newly modified output sequence is subsequently used as the input to the DQN for the next decoding iteration. In each iteration, we also bias the reinforcement learning's attention to explore sequence portions which are previously difficult to be decoded. For evaluation, the proposed strategy was trained to decode ten thousands natural sentences. Our experiments indicate that, when compared to a left-to-right greedy beam search LSTM decoder, the proposed method performed competitively well when decoding sentences from the training set, but significantly outperformed the baseline when decoding unseen sentences, in terms of BLEU score obtained.

Xiaodan Zhu, Parinaz Sobhani, Hongyu Guo

The chain-structured long short-term memory (LSTM) has showed to be effective in a wide range of problems such as speech recognition and machine translation. In this paper, we propose to extend it to tree structures, in which a memory cell can reflect the history memories of multiple child cells or multiple descendant cells in a recursive process. We call the model S-LSTM, which provides a principled way of considering long-distance interaction over hierarchies, e.g., language or image parse structures. We leverage the models for semantic composition to understand the meaning of text, a fundamental problem in natural language understanding, and show that it outperforms a state-of-the-art recursive model by replacing its composition layers with the S-LSTM memory blocks. We also show that utilizing the given structures is helpful in achieving a performance better than that without considering the structures.