arXiv subjects

Xiaomin Fang

Publications and source records attributed to Xiaomin Fang.

27 records · Page 2Linked to original sources

arXiv2022

TCR: A Transformer Based Deep Network for Predicting Cancer Drugs Response

Predicting clinical outcomes to anti-cancer drugs on a personalized basis is challenging in cancer treatment due to the heterogeneity of tumors. Traditional computational efforts have been made to model the effect of drug response on individual samples depicted by their molecular profile, yet overfitting occurs because of the high dimension for omics data, hindering models from clinical application. Recent research shows that deep learning is a promising approach to build drug response models by learning alignment patterns between drugs and samples. However, existing studies employed the simple feature fusion strategy and only considered the drug features as a whole representation while ignoring the substructure information that may play a vital role when aligning drugs and genes. Hereby in this paper, we propose TCR (Transformer based network for Cancer drug Response) to predict anti-cancer drug response. By utilizing an attention mechanism, TCR is able to learn the interactions between drug atom/sub-structure and molecular signatures efficiently in our study. Furthermore, a dual loss function and cross sampling strategy were designed to improve the prediction power of TCR. We show that TCR outperformed all other methods under various data splitting strategies on all evaluation matrices (some with significant improvement). Extensive experiments demonstrate that TCR shows significantly improved generalization ability on independent in-vitro experiments and in-vivo real patient data. Our study highlights the prediction power of TCR and its potential value for cancer drug repurpose and precision oncology treatment.

cs.LG↗

arXiv2022

HelixADMET: a robust and endpoint extensible ADMET system incorporating self-supervised knowledge transfer

Accurate ADMET (an abbreviation for "absorption, distribution, metabolism, excretion, and toxicity") predictions can efficiently screen out undesirable drug candidates in the early stage of drug discovery. In recent years, multiple comprehensive ADMET systems that adopt advanced machine learning models have been developed, providing services to estimate multiple endpoints. However, those ADMET systems usually suffer from weak extrapolation ability. First, due to the lack of labelled data for each endpoint, typical machine learning models perform frail for the molecules with unobserved scaffolds. Second, most systems only provide fixed built-in endpoints and cannot be customised to satisfy various research requirements. To this end, we develop a robust and endpoint extensible ADMET system, HelixADMET (H-ADMET). H-ADMET incorporates the concept of self-supervised learning to produce a robust pre-trained model. The model is then fine-tuned with a multi-task and multi-stage framework to transfer knowledge between ADMET endpoints, auxiliary tasks, and self-supervised tasks. Our results demonstrate that H-ADMET achieves an overall improvement of 4%, compared with existing ADMET systems on comparable endpoints. Additionally, the pre-trained model provided by H-ADMET can be fine-tuned to generate new and customised ADMET endpoints, meeting various demands of drug research and development requirements.

q-bio.BM↗

arXiv2022

ChemRL-GEM: Geometry Enhanced Molecular Representation Learning for Property Prediction

Effective molecular representation learning is of great importance to facilitate molecular property prediction, which is a fundamental task for the drug and material industry. Recent advances in graph neural networks (GNNs) have shown great promise in applying GNNs for molecular representation learning. Moreover, a few recent studies have also demonstrated successful applications of self-supervised learning methods to pre-train the GNNs to overcome the problem of insufficient labeled molecules. However, existing GNNs and pre-training strategies usually treat molecules as topological graph data without fully utilizing the molecular geometry information. Whereas, the three-dimensional (3D) spatial structure of a molecule, a.k.a molecular geometry, is one of the most critical factors for determining molecular physical, chemical, and biological properties. To this end, we propose a novel Geometry Enhanced Molecular representation learning method (GEM) for Chemical Representation Learning (ChemRL). At first, we design a geometry-based GNN architecture that simultaneously models atoms, bonds, and bond angles in a molecule. To be specific, we devised double graphs for a molecule: The first one encodes the atom-bond relations; The second one encodes bond-angle relations. Moreover, on top of the devised GNN architecture, we propose several novel geometry-level self-supervised learning strategies to learn spatial knowledge by utilizing the local and global molecular 3D structures. We compare ChemRL-GEM with various state-of-the-art (SOTA) baselines on different molecular benchmarks and exhibit that ChemRL-GEM can significantly outperform all baselines in both regression and classification tasks. For example, the experimental results show an overall improvement of 8.8% on average compared to SOTA baselines on the regression tasks, demonstrating the superiority of the proposed method.

cs.LG↗

arXiv2021

Docking-based Virtual Screening with Multi-Task Learning

Machine learning shows great potential in virtual screening for drug discovery. Current efforts on accelerating docking-based virtual screening do not consider using existing data of other previously developed targets. To make use of the knowledge of the other targets and take advantage of the existing data, in this work, we apply multi-task learning to the problem of docking-based virtual screening. With two large docking datasets, the results of extensive experiments show that multi-task learning can achieve better performances on docking score prediction. By learning knowledge across multiple targets, the model trained by multi-task learning shows a better ability to adapt to a new target. Additional empirical study shows that other problems in drug discovery, such as the experimental drug-target affinity prediction, may also benefit from multi-task learning. Our results demonstrate that multi-task learning is a promising machine learning approach for docking-based virtual screening and accelerating the process of drug discovery.

cs.LG↗

arXiv2021

Multimodal Pre-Training Model for Sequence-based Prediction of Protein-Protein Interaction

Protein-protein interactions (PPIs) are essentials for many biological processes where two or more proteins physically bind together to achieve their functions. Modeling PPIs is useful for many biomedical applications, such as vaccine design, antibody therapeutics, and peptide drug discovery. Pre-training a protein model to learn effective representation is critical for PPIs. Most pre-training models for PPIs are sequence-based, which naively adopt the language models used in natural language processing to amino acid sequences. More advanced works utilize the structure-aware pre-training technique, taking advantage of the contact maps of known protein structures. However, neither sequences nor contact maps can fully characterize structures and functions of the proteins, which are closely related to the PPI problem. Inspired by this insight, we propose a multimodal protein pre-training model with three modalities: sequence, structure, and function (S2F). Notably, instead of using contact maps to learn the amino acid-level rigid structures, we encode the structure feature with the topology complex of point clouds of heavy atoms. It allows our model to learn structural information about not only the backbones but also the side chains. Moreover, our model incorporates the knowledge from the functional description of proteins extracted from literature or manual annotations. Our experiments show that the S2F learns protein embeddings that achieve good performances on a variety of PPIs tasks, including cross-species PPI, antibody-antigen affinity prediction, antibody neutralization prediction for SARS-CoV-2, and mutation-driven binding affinity change prediction.

q-bio.BM↗

arXiv2021

LiteGEM: Lite Geometry Enhanced Molecular Representation Learning for Quantum Property Prediction

In this report, we (SuperHelix team) present our solution to KDD Cup 2021-PCQM4M-LSC, a large-scale quantum chemistry dataset on predicting HOMO-LUMO gap of molecules. Our solution, Lite Geometry Enhanced Molecular representation learning (LiteGEM) achieves a mean absolute error (MAE) of 0.1204 on the test set with the help of deep graph neural networks and various self-supervised learning tasks. The code of the framework can be found in https://github.com/PaddlePaddle/PaddleHelix/tree/dev/competition/kddcup2021-PCQM4M-LSC/.

physics.chem-ph↗

arXiv2020

MBCAL: Sample Efficient and Variance Reduced Reinforcement Learning for Recommender Systems

In recommender systems such as news feed stream, it is essential to optimize the long-term utilities in the continuous user-system interaction processes. Previous works have proved the capability of reinforcement learning in this problem. However, there are many practical challenges to implement deep reinforcement learning in online systems, including low sample efficiency, uncontrollable risks, and excessive variances. To address these issues, we propose a novel reinforcement learning method, namely model-based counterfactual advantage learning (MBCAL). The proposed method takes advantage of the characteristics of recommender systems and draws ideas from the model-based reinforcement learning method for higher sample efficiency. It has two components: an environment model that predicts the instant user behavior one-by-one in an auto-regressive form, and a future advantage model that predicts the future utility. To alleviate the impact of excessive variance when learning the future advantage model, we employ counterfactual comparisons derived from the environment model. In consequence, the proposed method possesses high sample efficiency and significantly lower variance; Also, it is able to use existing user logs to avoid the risks of starting from scratch. In contrast to its capability, its implementation cost is relatively low, which fits well with practical systems. Theoretical analysis and elaborate experiments are presented. Results show that the proposed method transcends the other supervised learning and RL-based methods in both sample efficiency and asymptotic performances.

cs.IR↗

arXiv2019

Sequential Evaluation and Generation Framework for Combinatorial Recommender System

In the combinatorial recommender systems, multiple items are fed to the user at one time in the result page, where the correlations among the items have impact on the user behavior. In this work, we model the combinatorial recommendation as the problem of generating a sequence(ordered list) of items from a candidate set, with the target of maximizing the expected overall utility(e.g. total clicks) of the sequence. Toward solving this problem, we propose the Evaluation-Generation framework. On the one hand of this framework, an evaluation model is trained to evaluate the expected overall utility, by fully considering the user, item information and the correlations among the co-exposed items. On the other hand, generation policies based on heuristic searching or reinforcement learning are devised to generate potential high-quality sequences, from which the evaluation model select one to expose. We propose effective model architectures and learning metrics under this framework. We also offer series of offline tests to thoroughly investigate the performance of the proposed framework, as supplements to the online experiments. Our results show obvious increase in performance compared with the previous solutions.

cs.IR↗

arXiv2018

Real time expert system for anomaly detection of aerators based on computer vision technology and existing surveillance cameras

Aerators are essential and crucial auxiliary devices in intensive culture, especially in industrial culture in China. The traditional methods cannot accurately detect abnormal condition of aerators in time. Surveillance cameras are widely used as visual perception modules of the Internet of Things, and then using these widely existing surveillance cameras to realize real-time anomaly detection of aerators is a cost-free and easy-to-promote method. However, it is difficult to develop such an expert system due to some technical and applied challenges, e.g., illumination, occlusion, complex background, etc. To tackle these aforementioned challenges, we propose a real-time expert system based on computer vision technology and existing surveillance cameras for anomaly detection of aerators, which consists of two modules, i.e., object region detection and working state detection. First, it is difficult to detect the working state for some small object regions in whole images, and the time complexity of global feature comparison is also high, so we present an object region detection method based on the region proposal idea. Moreover, we propose a novel algorithm called reference frame Kanade-Lucas-Tomasi (RF-KLT) algorithm for motion feature extraction in fixed regions. Then, we present a dimension reduction method of time series for establishing a feature dataset with obvious boundaries between classes. Finally, we use machine learning algorithms to build the feature classifier. The experimental results in both the actual video dataset and the augmented video dataset show that the accuracy for detecting object region and working state of aerators is 100% and 99.9% respectively, and the detection speed is 77-333 frames per second (FPS) according to the different types of surveillance cameras.

cs.CV↗