arXiv subjects

Xingyi Cheng

Publications and source records attributed to Xingyi Cheng.

At least 19 recordsLinked to original sources

arXiv2026

Region of Interest Segmentation and Morphological Analysis for Membranes in Cryo-Electron Tomography

Cryo-electron tomography (cryo-ET) enables high resolution, three-dimensional reconstruction of biological structures, including membranes and membrane proteins. Identification of regions of interest (ROIs) is central to scientific imaging, as it enables isolation and quantitative analysis of specific structural features within complex datasets. In practice, however, ROIs are typically derived indirectly through full structure segmentation followed by post hoc analysis. This limitation is especially apparent for continuous and geometrically complex structures such as membranes, which are segmented as single entities. Here, we developed TomoROIS-SurfORA, a two step framework for direct, shape-agnostic ROI segmentation and morphological surface analysis. TomoROIS performs deep learning-based ROI segmentation and can be trained from scratch using small annotated datasets, enabling practical application across diverse imaging data. SurfORA processes segmented structures as point clouds and surface meshes to extract quantitative morphological features, including inter-membrane distances, curvature, and surface roughness. It supports both closed and open surfaces, with specific considerations for open surfaces, which are common in cryo-ET due to the missing wedge effect. We demonstrate both tools using in vitro reconstituted membrane systems containing deformable vesicles with complex geometries, enabling automatic quantitative analysis of membrane contact sites and remodeling events such as invagination. While demonstrated here on cryo-ET membrane data, the combined approach is applicable to ROI detection and surface analysis in broader scientific imaging contexts.

cs.CV↗

arXiv2025

Protein Inverse Folding From Structure Feedback

The inverse folding problem, aiming to design amino acid sequences that fold into desired three-dimensional structures, is pivotal for various biotechnological applications. Here, we introduce a novel approach leveraging Direct Preference Optimization (DPO) to fine-tune an inverse folding model using feedback from a protein folding model. Given a target protein structure, we begin by sampling candidate sequences from the inverse-folding model, then predict the three-dimensional structure of each sequence with the folding model to generate pairwise structural-preference labels. These labels are used to fine-tune the inverse-folding model under the DPO objective. Our results on the CATH 4.2 test set demonstrate that DPO fine-tuning not only improves sequence recovery of baseline models but also leads to a significant improvement in average TM-Score from 0.77 to 0.81, indicating enhanced structure similarity. Furthermore, iterative application of our DPO-based method on challenging protein structures yields substantial gains, with an average TM-Score increase of 79.5\% with regard to the baseline model. This work establishes a promising direction for enhancing protein sequence design ability from structure feedback by effectively utilizing preference optimization.

cs.LG↗

arXiv2024

Training Compute-Optimal Protein Language Models

We explore optimally training protein language models, an area of significant interest in biological research where guidance on best practices is limited. Most models are trained with extensive compute resources until performance gains plateau, focusing primarily on increasing model sizes rather than optimizing the efficient compute frontier that balances performance and compute budgets. Our investigation is grounded in a massive dataset consisting of 939 million protein sequences. We trained over 300 models ranging from 3.5 million to 10.7 billion parameters on 5 to 200 billion unique tokens, to investigate the relations between model sizes, training token numbers, and objectives. First, we observed the effect of diminishing returns for the Causal Language Model (CLM) and that of overfitting for the Masked Language Model~(MLM) when repeating the commonly used Uniref database. To address this, we included metagenomic protein sequences in the training set to increase the diversity and avoid the plateau or overfitting effects. Second, we obtained the scaling laws of CLM and MLM on Transformer, tailored to the specific characteristics of protein sequence data. Third, we observe a transfer scaling phenomenon from CLM to MLM, further demonstrating the effectiveness of transfer through scaling behaviors based on estimated Effectively Transferred Tokens. Finally, to validate our scaling laws, we compare the large-scale versions of ESM-2 and PROGEN2 on downstream tasks, encompassing evaluations of protein generation as well as structure- and function-related tasks, all within less or equivalent pre-training compute budgets.

cs.LG↗

arXiv2024

MSAGPT: Neural Prompting Protein Structure Prediction via MSA Generative Pre-Training

Multiple Sequence Alignment (MSA) plays a pivotal role in unveiling the evolutionary trajectories of protein families. The accuracy of protein structure predictions is often compromised for protein sequences that lack sufficient homologous information to construct high quality MSA. Although various methods have been proposed to generate virtual MSA under these conditions, they fall short in comprehensively capturing the intricate coevolutionary patterns within MSA or require guidance from external oracle models. Here we introduce MSAGPT, a novel approach to prompt protein structure predictions via MSA generative pretraining in the low MSA regime. MSAGPT employs a simple yet effective 2D evolutionary positional encoding scheme to model complex evolutionary patterns. Endowed by this, its flexible 1D MSA decoding framework facilitates zero or few shot learning. Moreover, we demonstrate that leveraging the feedback from AlphaFold2 can further enhance the model capacity via Rejective Fine tuning (RFT) and Reinforcement Learning from AF2 Feedback (RLAF). Extensive experiments confirm the efficacy of MSAGPT in generating faithful virtual MSA to enhance the structure prediction accuracy. The transfer learning capabilities also highlight its great potential for facilitating other protein tasks.

q-bio.BM↗

arXiv2024

xTrimoPGLM: Unified 100B-Scale Pre-trained Transformer for Deciphering the Language of Protein

Protein language models have shown remarkable success in learning biological information from protein sequences. However, most existing models are limited by either autoencoding or autoregressive pre-training objectives, which makes them struggle to handle protein understanding and generation tasks concurrently. We propose a unified protein language model, xTrimoPGLM, to address these two types of tasks simultaneously through an innovative pre-training framework. Our key technical contribution is an exploration of the compatibility and the potential for joint optimization of the two types of objectives, which has led to a strategy for training xTrimoPGLM at an unprecedented scale of 100 billion parameters and 1 trillion training tokens. Our extensive experiments reveal that 1) xTrimoPGLM significantly outperforms other advanced baselines in 18 protein understanding benchmarks across four categories. The model also facilitates an atomic-resolution view of protein structures, leading to an advanced 3D structural prediction model that surpasses existing language model-based tools. 2) xTrimoPGLM not only can generate de novo protein sequences following the principles of natural ones, but also can perform programmable generation after supervised fine-tuning (SFT) on curated sequences. These results highlight the substantial capability and versatility of xTrimoPGLM in understanding and generating protein sequences, contributing to the evolving landscape of foundation models in protein science.

q-bio.QM↗

arXiv2023

Linker-Tuning: Optimizing Continuous Prompts for Heterodimeric Protein Prediction

Predicting the structure of interacting chains is crucial for understanding biological systems and developing new drugs. Large-scale pre-trained Protein Language Models (PLMs), such as ESM2, have shown impressive abilities in extracting biologically meaningful representations for protein structure prediction. In this paper, we show that ESMFold, which has been successful in computing accurate atomic structures for single-chain proteins, can be adapted to predict the heterodimer structures in a lightweight manner. We propose Linker-tuning, which learns a continuous prompt to connect the two chains in a dimer before running it as a single sequence in ESMFold. Experiment results show that our method successfully predicts 56.98% of interfaces on the i.i.d. heterodimer test set, with an absolute improvement of +12.79% over the ESMFold-Linker baseline. Furthermore, our model can generalize well to the out-of-distribution (OOD) test set HeteroTest2 and two antibody test sets Fab and Fv while being $9\times$ faster than AF-Multimer.

q-bio.BM↗

arXiv2023

xTrimoGene: An Efficient and Scalable Representation Learner for Single-Cell RNA-Seq Data

Advances in high-throughput sequencing technology have led to significant progress in measuring gene expressions at the single-cell level. The amount of publicly available single-cell RNA-seq (scRNA-seq) data is already surpassing 50M records for humans with each record measuring 20,000 genes. This highlights the need for unsupervised representation learning to fully ingest these data, yet classical transformer architectures are prohibitive to train on such data in terms of both computation and memory. To address this challenge, we propose a novel asymmetric encoder-decoder transformer for scRNA-seq data, called xTrimoGene$^\alpha$ (or xTrimoGene for short), which leverages the sparse characteristic of the data to scale up the pre-training. This scalable design of xTrimoGene reduces FLOPs by one to two orders of magnitude compared to classical transformers while maintaining high accuracy, enabling us to train the largest transformer models over the largest scRNA-seq dataset today. Our experiments also show that the performance of xTrimoGene improves as we scale up the model sizes, and it also leads to SOTA performance over various downstream tasks, such as cell type annotation, perturb-seq effect prediction, and drug combination prediction. xTrimoGene model is now available for use as a service via the following link: https://api.biomap.com/xTrimoGene/apply.

cs.LG↗

arXiv2023

Won't Get Fooled Again: Answering Questions with False Premises

Pre-trained language models (PLMs) have shown unprecedented potential in various fields, especially as the backbones for question-answering (QA) systems. However, they tend to be easily deceived by tricky questions such as "How many eyes does the sun have?". Such frailties of PLMs often allude to the lack of knowledge within them. In this paper, we find that the PLMs already possess the knowledge required to rebut such questions, and the key is how to activate the knowledge. To systematize this observation, we investigate the PLMs' responses to one kind of tricky questions, i.e., the false premises questions (FPQs). We annotate a FalseQA dataset containing 2365 human-written FPQs, with the corresponding explanations for the false premises and the revised true premise questions. Using FalseQA, we discover that PLMs are capable of discriminating FPQs by fine-tuning on moderate numbers (e.g., 256) of examples. PLMs also generate reasonable explanations for the false premise, which serve as rebuttals. Further replaying a few general questions during training allows PLMs to excel on FPQs and general questions simultaneously. Our work suggests that once the rebuttal ability is stimulated, knowledge inside the PLMs can be effectively utilized to handle FPQs, which incentivizes the research on PLM-based QA systems.

cs.CL↗

arXiv2023

Revisiting Out-of-distribution Robustness in NLP: Benchmark, Analysis, and LLMs Evaluations

This paper reexamines the research on out-of-distribution (OOD) robustness in the field of NLP. We find that the distribution shift settings in previous studies commonly lack adequate challenges, hindering the accurate evaluation of OOD robustness. To address these issues, we propose a benchmark construction protocol that ensures clear differentiation and challenging distribution shifts. Then we introduce BOSS, a Benchmark suite for Out-of-distribution robustneSS evaluation covering 5 tasks and 20 datasets. Based on BOSS, we conduct a series of experiments on pre-trained language models for analysis and evaluation of OOD robustness. First, for vanilla fine-tuning, we examine the relationship between in-distribution (ID) and OOD performance. We identify three typical types that unveil the inner learning mechanism, which could potentially facilitate the forecasting of OOD robustness, correlating with the advancements on ID datasets. Then, we evaluate 5 classic methods on BOSS and find that, despite exhibiting some effectiveness in specific cases, they do not offer significant improvement compared to vanilla fine-tuning. Further, we evaluate 5 LLMs with various adaptation paradigms and find that when sufficient ID data is available, fine-tuning domain-specific models outperform LLMs on ID examples significantly. However, in the case of OOD instances, prioritizing LLMs with in-context learning yields better results. We identify that both fine-tuned small models and LLMs face challenges in effectively addressing downstream tasks. The code is public at \url{https://github.com/lifan-yuan/OOD_NLP}.

cs.CL↗

arXiv2021

K-AID: Enhancing Pre-trained Language Models with Domain Knowledge for Question Answering

Knowledge enhanced pre-trained language models (K-PLMs) are shown to be effective for many public tasks in the literature but few of them have been successfully applied in practice. To address this problem, we propose K-AID, a systematic approach that includes a low-cost knowledge acquisition process for acquiring domain knowledge, an effective knowledge infusion module for improving model performance, and a knowledge distillation component for reducing the model size and deploying K-PLMs on resource-restricted devices (e.g., CPU) for real-world application. Importantly, instead of capturing entity knowledge like the majority of existing K-PLMs, our approach captures relational knowledge, which contributes to better-improving sentence-level text classification and text matching tasks that play a key role in question answering (QA). We conducted a set of experiments on five text classification tasks and three text matching tasks from three domains, namely E-commerce, Government, and Film&TV, and performed online A/B tests in E-commerce. Experimental results show that our approach is able to achieve substantial improvement on sentence-level question answering tasks and bring beneficial business value in industrial settings.

cs.AI↗

arXiv2021

Evaluating Modules in Graph Contrastive Learning

The recent emergence of contrastive learning approaches facilitates the application on graph representation learning (GRL), introducing graph contrastive learning (GCL) into the literature. These methods contrast semantically similar and dissimilar sample pairs to encode the semantics into node or graph embeddings. However, most existing works only performed \textbf{model-level} evaluation, and did not explore the combination space of modules for more comprehensive and systematic studies. For effective \textbf{module-level} evaluation, we propose a framework that decomposes GCL models into four modules: (1) a \textbf{sampler} to generate anchor, positive and negative data samples (nodes or graphs); (2) an \textbf{encoder} and a \textbf{readout} function to get sample embeddings; (3) a \textbf{discriminator} to score each sample pair (anchor-positive and anchor-negative); and (4) an \textbf{estimator} to define the loss function. Based on this framework, we conduct controlled experiments over a wide range of architectural designs and hyperparameter settings on node and graph classification tasks. Specifically, we manage to quantify the impact of a single module, investigate the interaction between modules, and compare the overall performance with current model architectures. Our key findings include a set of module-level guidelines for GCL, e.g., simple samplers from LINE and DeepWalk are strong and robust; an MLP encoder associated with Sum readout could achieve competitive performance on graph classification. Finally, we release our implementations and results as OpenGCL, a modularized toolkit that allows convenient reproduction, standard model and module evaluation, and easy extension. OpenGCL is available at \url{https://github.com/thunlp/OpenGCL}.

cs.LG↗

arXiv2021

Dual-View Distilled BERT for Sentence Embedding

Recently, BERT realized significant progress for sentence matching via word-level cross sentence attention. However, the performance significantly drops when using siamese BERT-networks to derive two sentence embeddings, which fall short in capturing the global semantic since the word-level attention between two sentences is absent. In this paper, we propose a Dual-view distilled BERT~(DvBERT) for sentence matching with sentence embeddings. Our method deals with a sentence pair from two distinct views, i.e., Siamese View and Interaction View. Siamese View is the backbone where we generate sentence embeddings. Interaction View integrates the cross sentence interaction as multiple teachers to boost the representation ability of sentence embeddings. Experiments on six STS tasks show that our method outperforms the state-of-the-art sentence embedding methods significantly.

cs.AI↗

arXiv2020

Question Directed Graph Attention Network for Numerical Reasoning over Text

Numerical reasoning over texts, such as addition, subtraction, sorting and counting, is a challenging machine reading comprehension task, since it requires both natural language understanding and arithmetic computation. To address this challenge, we propose a heterogeneous graph representation for the context of the passage and question needed for such reasoning, and design a question directed graph attention network to drive multi-step numerical reasoning over this context graph. The code link is at: https://github.com/emnlp2020qdgat/QDGAT

cs.AI↗

arXiv2020

A Workflow for Exploring Ligand Dissociation from a Macromolecule: Efficient Random Acceleration Molecular Dynamics Simulation and Interaction Fingerprints Analysis of Ligand Trajectories

The dissociation of ligands from proteins and other biomacromolecules occurs over a wide range of timescales. For most pharmaceutically relevant inhibitors, these timescales are far beyond those that are accessible by conventional molecular dynamics (MD) simulation. Consequently, to explore ligand egress mechanisms and compute dissociation rates, it is necessary to enhance the sampling of ligand unbinding. Random Acceleration MD (RAMD) is a simple method to enhance ligand egress from a macromolecular binding site, which enables the exploration of ligand egress routes without prior knowledge of the reaction coordinates. Furthermore, the tauRAMD procedure can be used to compute the relative residence times of ligands. When combined with a machine-learning analysis of protein-ligand interaction fingerprints (IFPs), molecular features that affect ligand unbinding kinetics can be identified. Here, we describe the implementation of RAMD in GROMACS 2020, which provides significantly improved computational performance, with scaling to large molecular systems. For the automated analysis of RAMD results, we developed MD-IFP, a set of tools for the generation of IFPs along unbinding trajectories and for their use in the exploration of ligand dynamics. We demonstrate that the analysis of ligand dissociation trajectories by mapping them onto the IFP space enables the characterization of ligand dissociation routes and metastable states. The combined implementation of RAMD and MD-IFP provides a computationally efficient and freely available workflow that can be applied to hundreds of compounds in a reasonable computational time and will facilitate the use of tauRAMD in drug design.

q-bio.BM↗

arXiv2020

SpellGCN: Incorporating Phonological and Visual Similarities into Language Models for Chinese Spelling Check

Chinese Spelling Check (CSC) is a task to detect and correct spelling errors in Chinese natural language. Existing methods have made attempts to incorporate the similarity knowledge between Chinese characters. However, they take the similarity knowledge as either an external input resource or just heuristic rules. This paper proposes to incorporate phonological and visual similarity knowledge into language models for CSC via a specialized graph convolutional network (SpellGCN). The model builds a graph over the characters, and SpellGCN is learned to map this graph into a set of inter-dependent character classifiers. These classifiers are applied to the representations extracted by another network, such as BERT, enabling the whole network to be end-to-end trainable. Experiments (The dataset and all code for this paper are available at https://github.com/ACL2020SpellGCN/SpellGCN) are conducted on three human-annotated datasets. Our method achieves superior performance against previous models by a large margin.

cs.CL↗

arXiv2019

Symmetric Regularization based BERT for Pair-wise Semantic Reasoning

The ability of semantic reasoning over the sentence pair is essential for many natural language understanding tasks, e.g., natural language inference and machine reading comprehension. A recent significant improvement in these tasks comes from BERT. As reported, the next sentence prediction (NSP) in BERT, which learns the contextual relationship between two sentences, is of great significance for downstream problems with sentence-pair input. Despite the effectiveness of NSP, we suggest that NSP still lacks the essential signal to distinguish between entailment and shallow correlation. To remedy this, we propose to augment the NSP task to a 3-class categorization task, which includes a category for previous sentence prediction (PSP). The involvement of PSP encourages the model to focus on the informative semantics to determine the sentence order, thereby improves the ability of semantic understanding. This simple modification yields remarkable improvement against vanilla BERT. To further incorporate the document-level information, the scope of NSP and PSP is expanded into a broader range, i.e., NSP and PSP also include close but nonsuccessive sentences, the noise of which is mitigated by the label-smoothing technique. Both qualitative and quantitative experimental results demonstrate the effectiveness of the proposed method. Our method consistently improves the performance on the NLI and MRC benchmarks, including the challenging HANS dataset \cite{hans}, suggesting that the document-level task is still promising for the pre-training.

cs.CL↗

arXiv2019

BERT-Based Multi-Head Selection for Joint Entity-Relation Extraction

In this paper, we report our method for the Information Extraction task in 2019 Language and Intelligence Challenge. We incorporate BERT into the multi-head selection framework for joint entity-relation extraction. This model extends existing approaches from three perspectives. First, BERT is adopted as a feature extraction layer at the bottom of the multi-head selection framework. We further optimize BERT by introducing a semantic-enhanced task during BERT pre-training. Second, we introduce a large-scale Baidu Baike corpus for entity recognition pre-training, which is of weekly supervised learning since there is no actual named entity label. Third, soft label embedding is proposed to effectively transmit information between entity recognition and relation extraction. Combining these three contributions, we enhance the information extracting ability of the multi-head selection model and achieve F1-score 0.876 on testset-1 with a single model. By ensembling four variants of our model, we finally achieve F1 score 0.892 (1st place) on testset-1 and F1 score 0.8924 (2nd place) on testset-2.

cs.CL↗

arXiv2019

An end-to-end Neural Network Framework for Text Clustering

The unsupervised text clustering is one of the major tasks in natural language processing (NLP) and remains a difficult and complex problem. Conventional \mbox{methods} generally treat this task using separated steps, including text representation learning and clustering the representations. As an improvement, neural methods have also been introduced for continuous representation learning to address the sparsity problem. However, the multi-step process still deviates from the unified optimization target. Especially the second step of cluster is generally performed with conventional methods such as k-Means. We propose a pure neural framework for text clustering in an end-to-end manner. It jointly learns the text representation and the clustering model. Our model works well when the context can be obtained, which is nearly always the case in the field of NLP. We have our method \mbox{evaluated} on two widely used benchmarks: IMDB movie reviews for sentiment classification and $20$-Newsgroup for topic categorization. Despite its simplicity, experiments show the model outperforms previous clustering methods by a large margin. Furthermore, the model is also verified on English wiki dataset as a large corpus.

cs.CL↗