arXiv subjects

Shufang Xie

Publications and source records attributed to Shufang Xie.

34 records · Page 2Linked to original sources

arXiv2023

MolXPT: Wrapping Molecules with Text for Generative Pre-training

Generative pre-trained Transformer (GPT) has demonstrates its great success in natural language processing and related techniques have been adapted into molecular modeling. Considering that text is the most important record for scientific discovery, in this paper, we propose MolXPT, a unified language model of text and molecules pre-trained on SMILES (a sequence representation of molecules) wrapped by text. Briefly, we detect the molecule names in each sequence and replace them to the corresponding SMILES. In this way, the SMILES could leverage the information from surrounding text, and vice versa. The above wrapped sequences, text sequences from PubMed and SMILES sequences from PubChem are all fed into a language model for pre-training. Experimental results demonstrate that MolXPT outperforms strong baselines of molecular property prediction on MoleculeNet, performs comparably to the best model in text-molecule translation while using less than half of its parameters, and enables zero-shot molecular generation without finetuning.

cs.CL↗

arXiv2023

What are the Desired Characteristics of Calibration Sets? Identifying Correlates on Long Form Scientific Summarization

Summarization models often generate text that is poorly calibrated to quality metrics because they are trained to maximize the likelihood of a single reference (MLE). To address this, recent work has added a calibration step, which exposes a model to its own ranked outputs to improve relevance or, in a separate line of work, contrasts positive and negative sets to improve faithfulness. While effective, much of this work has focused on how to generate and optimize these sets. Less is known about why one setup is more effective than another. In this work, we uncover the underlying characteristics of effective sets. For each training instance, we form a large, diverse pool of candidates and systematically vary the subsets used for calibration fine-tuning. Each selection strategy targets distinct aspects of the sets, such as lexical diversity or the size of the gap between positive and negatives. On three diverse scientific long-form summarization datasets (spanning biomedical, clinical, and chemical domains), we find, among others, that faithfulness calibration is optimal when the negative sets are extractive and more likely to be generated, whereas for relevance calibration, the metric margin between candidates should be maximized and surprise--the disagreement between model and metric defined candidate rankings--minimized. Code to create, select, and optimize calibration sets is available at https://github.com/griff4692/calibrating-summaries

cs.CL↗

arXiv2023

ResiDual: Transformer with Dual Residual Connections

Transformer networks have become the preferred architecture for many tasks due to their state-of-the-art performance. However, the optimal way to implement residual connections in Transformer, which are essential for effective training, is still debated. Two widely used variants are the Post-Layer-Normalization (Post-LN) and Pre-Layer-Normalization (Pre-LN) Transformers, which apply layer normalization after each residual block's output or before each residual block's input, respectively. While both variants enjoy their advantages, they also suffer from severe limitations: Post-LN causes gradient vanishing issue that hinders training deep Transformers, and Pre-LN causes representation collapse issue that limits model capacity. In this paper, we propose ResiDual, a novel Transformer architecture with Pre-Post-LN (PPLN), which fuses the connections in Post-LN and Pre-LN together and inherits their advantages while avoids their limitations. We conduct both theoretical analyses and empirical experiments to verify the effectiveness of ResiDual. Theoretically, we prove that ResiDual has a lower bound on the gradient to avoid the vanishing issue due to the residual connection from Pre-LN. Moreover, ResiDual also has diverse model representations to avoid the collapse issue due to the residual connection from Post-LN. Empirically, ResiDual outperforms both Post-LN and Pre-LN on several machine translation benchmarks across different network depths and data sizes. Thanks to the good theoretical and empirical performance, ResiDual Transformer can serve as a foundation architecture for different AI models (e.g., large language models). Our code is available at https://github.com/microsoft/ResiDual.

cs.CL↗

arXiv2023

De Novo Molecular Generation via Connection-aware Motif Mining

De novo molecular generation is an essential task for science discovery. Recently, fragment-based deep generative models have attracted much research attention due to their flexibility in generating novel molecules based on existing molecule fragments. However, the motif vocabulary, i.e., the collection of frequent fragments, is usually built upon heuristic rules, which brings difficulties to capturing common substructures from large amounts of molecules. In this work, we propose a new method, MiCaM, to generate molecules based on mined connection-aware motifs. Specifically, it leverages a data-driven algorithm to automatically discover motifs from a molecule library by iteratively merging subgraphs based on their frequency. The obtained motif vocabulary consists of not only molecular motifs (i.e., the frequent fragments), but also their connection information, indicating how the motifs are connected with each other. Based on the mined connection-aware motifs, MiCaM builds a connection-aware generator, which simultaneously picks up motifs and determines how they are connected. We test our method on distribution-learning benchmarks (i.e., generating novel molecules to resemble the distribution of a given training set) and goal-directed benchmarks (i.e., generating molecules with target properties), and achieve significant improvements over previous fragment-based baselines. Furthermore, we demonstrate that our method can effectively mine domain-specific motifs for different tasks.

cs.LG↗

arXiv2022

Direct Molecular Conformation Generation

Molecular conformation generation aims to generate three-dimensional coordinates of all the atoms in a molecule and is an important task in bioinformatics and pharmacology. Previous methods usually first predict the interatomic distances, the gradients of interatomic distances or the local structures (e.g., torsion angles) of a molecule, and then reconstruct its 3D conformation. How to directly generate the conformation without the above intermediate values is not fully explored. In this work, we propose a method that directly predicts the coordinates of atoms: (1) the loss function is invariant to roto-translation of coordinates and permutation of symmetric atoms; (2) the newly proposed model adaptively aggregates the bond and atom information and iteratively refines the coordinates of the generated conformation. Our method achieves the best results on GEOM-QM9 and GEOM-Drugs datasets. Further analysis shows that our generated conformations have closer properties (e.g., HOMO-LUMO gap) with the groundtruth conformations. In addition, our method improves molecular docking by providing better initial conformations. All the results demonstrate the effectiveness of our method and the great potential of the direct approach. The code is released at https://github.com/DirectMolecularConfGen/DMCG

cs.AI↗

arXiv2022

Incorporating Pre-training Paradigm for Antibody Sequence-Structure Co-design

Antibodies are versatile proteins that can bind to pathogens and provide effective protection for human body. Recently, deep learning-based computational antibody design has attracted popular attention since it automatically mines the antibody patterns from data that could be complementary to human experiences. However, the computational methods heavily rely on high-quality antibody structure data, which is quite limited. Besides, the complementarity-determining region (CDR), which is the key component of an antibody that determines the specificity and binding affinity, is highly variable and hard to predict. Therefore, the data limitation issue further raises the difficulty of CDR generation for antibodies. Fortunately, there exists a large amount of sequence data of antibodies that can help model the CDR and alleviate the reliance on structure data. By witnessing the success of pre-training models for protein modeling, in this paper, we develop the antibody pre-training language model and incorporate it into the (antigen-specific) antibody design model in a systemic way. Specifically, we first pre-train an antibody language model based on the sequence data, then propose a one-shot way for sequence and structure generation of CDR to avoid the heavy cost and error propagation from an autoregressive manner, and finally leverage the pre-trained antibody model for the antigen-specific antibody generation model with some carefully designed modules. Through various experiments, we show that our method achieves superior performances over previous baselines on different tasks, such as sequence and structure generation and antigen-binding CDR-H3 design.

q-bio.BM↗

arXiv2022

Tailoring Molecules for Protein Pockets: a Transformer-based Generative Solution for Structured-based Drug Design

Structure-based drug design is drawing growing attentions in computer-aided drug discovery. Compared with the virtual screening approach where a pre-defined library of compounds are computationally screened, de novo drug design based on the structure of a target protein can provide novel drug candidates. In this paper, we present a generative solution named TamGent (Target-aware molecule generator with Transformer) that can directly generate candidate drugs from scratch for a given target, overcoming the limits imposed by existing compound libraries. Following the Transformer framework (a state-of-the-art framework in deep learning), we design a variant of Transformer encoder to process 3D geometric information of targets and pre-train the Transformer decoder on 10 million compounds from PubChem for candidate drug generation. Systematical evaluation on candidate compounds generated for targets from DrugBank shows that both binding affinity and drugability are largely improved. TamGent outperforms previous baselines in terms of both effectiveness and efficiency. The method is further verified by generating candidate compounds for the SARS-CoV-2 main protease and the oncogenic mutant KRAS G12C. The results show that our method not only re-discovers previously verified drug molecules , but also generates novel molecules with better docking scores, expanding the compound pool and potentially leading to the discovery of novel drugs.

q-bio.BM↗

arXiv2022

Unified 2D and 3D Pre-Training of Molecular Representations

Molecular representation learning has attracted much attention recently. A molecule can be viewed as a 2D graph with nodes/atoms connected by edges/bonds, and can also be represented by a 3D conformation with 3-dimensional coordinates of all atoms. We note that most previous work handles 2D and 3D information separately, while jointly leveraging these two sources may foster a more informative representation. In this work, we explore this appealing idea and propose a new representation learning method based on a unified 2D and 3D pre-training. Atom coordinates and interatomic distances are encoded and then fused with atomic representations through graph neural networks. The model is pre-trained on three tasks: reconstruction of masked atoms and coordinates, 3D conformation generation conditioned on 2D graph, and 2D graph generation conditioned on 3D conformation. We evaluate our method on 11 downstream molecular property prediction tasks: 7 with 2D information only and 4 with both 2D and 3D information. Our method achieves state-of-the-art results on 10 tasks, and the average improvement on 2D-only tasks is 8.3%. Our method also achieves significant improvement on two 3D conformation generation tasks.

cs.LG↗

arXiv2022

Building Multilingual Machine Translation Systems That Serve Arbitrary X-Y Translations

Multilingual Neural Machine Translation (MNMT) enables one system to translate sentences from multiple source languages to multiple target languages, greatly reducing deployment costs compared with conventional bilingual systems. The MNMT training benefit, however, is often limited to many-to-one directions. The model suffers from poor performance in one-to-many and many-to-many with zero-shot setup. To address this issue, this paper discusses how to practically build MNMT systems that serve arbitrary X-Y translation directions while leveraging multilinguality with a two-stage training strategy of pretraining and finetuning. Experimenting with the WMT'21 multilingual translation task, we demonstrate that our systems outperform the conventional baselines of direct bilingual models and pivot translation models for most directions, averagely giving +6.0 and +4.1 BLEU, without the need for architecture change or extra data collection. Moreover, we also examine our proposed approach in an extremely large-scale data setting to accommodate practical deployment scenarios.

cs.CL↗

arXiv2022

RetroGraph: Retrosynthetic Planning with Graph Search

Retrosynthetic planning, which aims to find a reaction pathway to synthesize a target molecule, plays an important role in chemistry and drug discovery. This task is usually modeled as a search problem. Recently, data-driven methods have attracted many research interests and shown promising results for retrosynthetic planning. We observe that the same intermediate molecules are visited many times in the searching process, and they are usually independently treated in previous tree-based methods (e.g., AND-OR tree search, Monte Carlo tree search). Such redundancies make the search process inefficient. We propose a graph-based search policy that eliminates the redundant explorations of any intermediate molecules. As searching over a graph is more complicated than over a tree, we further adopt a graph neural network to guide the search over graphs. Meanwhile, our method can search a batch of targets together in the graph and remove the inter-target duplication in the tree-based search methods. Experimental results on two datasets demonstrate the effectiveness of our method. Especially on the widely used USPTO benchmark, we improve the search success rate to 99.47%, advancing previous state-of-the-art performance for 2.6 points.

cs.AI↗

arXiv2021

Discovering Drug-Target Interaction Knowledge from Biomedical Literature

The Interaction between Drugs and Targets (DTI) in human body plays a crucial role in biomedical science and applications. As millions of papers come out every year in the biomedical domain, automatically discovering DTI knowledge from biomedical literature, which are usually triplets about drugs, targets and their interaction, becomes an urgent demand in the industry. Existing methods of discovering biological knowledge are mainly extractive approaches that often require detailed annotations (e.g., all mentions of biological entities, relations between every two entity mentions, etc.). However, it is difficult and costly to obtain sufficient annotations due to the requirement of expert knowledge from biomedical domains. To overcome these difficulties, we explore the first end-to-end solution for this task by using generative approaches. We regard the DTI triplets as a sequence and use a Transformer-based model to directly generate them without using the detailed annotations of entities and relations. Further, we propose a semi-supervised method, which leverages the aforementioned end-to-end model to filter unlabeled literature and label them. Experimental results show that our method significantly outperforms extractive baselines on DTI discovery. We also create a dataset, KD-DTI, to advance this task and will release it to the community.

cs.CL↗

arXiv2021

Temporally Correlated Task Scheduling for Sequence Learning

Sequence learning has attracted much research attention from the machine learning community in recent years. In many applications, a sequence learning task is usually associated with multiple temporally correlated auxiliary tasks, which are different in terms of how much input information to use or which future step to predict. For example, (i) in simultaneous machine translation, one can conduct translation under different latency (i.e., how many input words to read/wait before translation); (ii) in stock trend forecasting, one can predict the price of a stock in different future days (e.g., tomorrow, the day after tomorrow). While it is clear that those temporally correlated tasks can help each other, there is a very limited exploration on how to better leverage multiple auxiliary tasks to boost the performance of the main task. In this work, we introduce a learnable scheduler to sequence learning, which can adaptively select auxiliary tasks for training depending on the model status and the current training data. The scheduler and the model for the main task are jointly trained through bi-level optimization. Experiments show that our method significantly improves the performance of simultaneous machine translation and stock trend forecasting.

cs.CL↗

arXiv2021

UniDrop: A Simple yet Effective Technique to Improve Transformer without Extra Cost

Transformer architecture achieves great success in abundant natural language processing tasks. The over-parameterization of the Transformer model has motivated plenty of works to alleviate its overfitting for superior performances. With some explorations, we find simple techniques such as dropout, can greatly boost model performance with a careful design. Therefore, in this paper, we integrate different dropout techniques into the training of Transformer models. Specifically, we propose an approach named UniDrop to unites three different dropout techniques from fine-grain to coarse-grain, i.e., feature dropout, structure dropout, and data dropout. Theoretically, we demonstrate that these three dropouts play different roles from regularization perspectives. Empirically, we conduct experiments on both neural machine translation and text classification benchmark datasets. Extensive results indicate that Transformer with UniDrop can achieve around 1.5 BLEU improvement on IWSLT14 translation tasks, and better accuracy for the classification even using strong pre-trained RoBERTa as backbone.

cs.CL↗

arXiv2021

IOT: Instance-wise Layer Reordering for Transformer Structures

With sequentially stacked self-attention, (optional) encoder-decoder attention, and feed-forward layers, Transformer achieves big success in natural language processing (NLP), and many variants have been proposed. Currently, almost all these models assume that the layer order is fixed and kept the same across data samples. We observe that different data samples actually favor different orders of the layers. Based on this observation, in this work, we break the assumption of the fixed layer order in the Transformer and introduce instance-wise layer reordering into the model structure. Our Instance-wise Ordered Transformer (IOT) can model variant functions by reordered layers, which enables each sample to select the better one to improve the model performance under the constraint of almost the same number of parameters. To achieve this, we introduce a light predictor with negligible parameter and inference cost to decide the most capable and favorable layer order for any input sequence. Experiments on 3 tasks (neural machine translation, abstractive summarization, and code generation) and 9 datasets demonstrate consistent improvements of our method. We further show that our method can also be applied to other architectures beyond Transformer. Our code is released at Github.

cs.CL↗

arXiv2021

Learning to Reweight with Deep Interactions

Recently, the concept of teaching has been introduced into machine learning, in which a teacher model is used to guide the training of a student model (which will be used in real tasks) through data selection, loss function design, etc. Learning to reweight, which is a specific kind of teaching that reweights training data using a teacher model, receives much attention due to its simplicity and effectiveness. In existing learning to reweight works, the teacher model only utilizes shallow/surface information such as training iteration number and loss/accuracy of the student model from training/validation sets, but ignores the internal states of the student model, which limits the potential of learning to reweight. In this work, we propose an improved data reweighting algorithm, in which the student model provides its internal states to the teacher model, and the teacher model returns adaptive weights of training samples to enhance the training of the student model. The teacher model is jointly trained with the student model using meta gradients propagated from a validation set. Experiments on image classification with clean/noisy labels and neural machine translation empirically demonstrate that our algorithm makes significant improvement over previous methods.

cs.LG↗

arXiv2020

Multi-branch Attentive Transformer

While the multi-branch architecture is one of the key ingredients to the success of computer vision tasks, it has not been well investigated in natural language processing, especially sequence learning tasks. In this work, we propose a simple yet effective variant of Transformer called multi-branch attentive Transformer (briefly, MAT), where the attention layer is the average of multiple branches and each branch is an independent multi-head attention layer. We leverage two training techniques to regularize the training: drop-branch, which randomly drops individual branches during training, and proximal initialization, which uses a pre-trained Transformer model to initialize multiple branches. Experiments on machine translation, code generation and natural language understanding demonstrate that such a simple variant of Transformer brings significant improvements. Our code is available at \url{https://github.com/HA-Transformer}.

cs.CL↗