Dataset Information

Improving antibody optimization ability of generative adversarial network through large language model.

ABSTRACT: Generative adversarial networks (GANs) have successfully generated functional protein sequences. However, traditional GANs often suffer from inherent randomness, resulting in a lower probability of obtaining desirable sequences. Due to the high cost of wet-lab experiments, the main goal of computer-aided antibody optimization is to identify high-quality candidate antibodies from a large range of possibilities, yet improving the ability of GANs to generate these desired antibodies is a challenge. In this study, we propose and evaluate a new GAN called the Language Model Guided Antibody Generative Adversarial Network (AbGAN-LMG). This GAN uses a language model as an input, harnessing such models' powerful representational capabilities to improve the GAN's generation of high-quality antibodies. We conducted a comprehensive evaluation of the antibody libraries and sequences generated by AbGAN-LMG for COVID-19 (SARS-CoV-2) and Middle East Respiratory Syndrome (MERS-CoV). Results indicate that AbGAN-LMG has learned the fundamental characteristics of antibodies and that it improved the diversity of the generated libraries. Additionally, when generating sequences using AZD-8895 as the target antibody for optimization, over 50% of the generated sequences exhibited better developability than AZD-8895 itself. Through molecular docking, we identified 70 antibodies that demonstrated higher affinity for the wild-type receptor-binding domain (RBD) of SARS-CoV-2 compared to AZD-8895. In conclusion, AbGAN-LMG demonstrates that language models used in conjunction with GANs can enable the generation of higher-quality libraries and candidate sequences, thereby improving the efficiency of antibody optimization. AbGAN-LMG is available at http://39.102.71.224:88/.

SUBMITTER: Zhao W

PROVIDER: S-EPMC10698008 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Improving antibody optimization ability of generative adversarial network through large language model.

Zhao Wenbin W Luo Xiaowei X Tong Fan F Zheng Xiangwen X Li Jing J Zhao Guangyu G Zhao Dongsheng D

Computational and structural biotechnology journal 20231123

Generative adversarial networks (GANs) have successfully generated functional protein sequences. However, traditional GANs often suffer from inherent randomness, resulting in a lower probability of obtaining desirable sequences. Due to the high cost of wet-lab experiments, the main goal of computer-aided antibody optimization is to identify high-quality candidate antibodies from a large range of possibilities, yet improving the ability of GANs to generate these desired antibodies is a challenge. ...[more]

PMID: 38074472

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Project description:Drug design is an important area of study for pharmaceutical businesses. However, low efficacy, off-target delivery, time consumption, and high cost are challenges and can create barriers that impact this process. Deep Learning models are emerging as a promising solution to perform de novo drug design, i.e., to generate drug-like molecules tailored to specific needs. However, stereochemistry was not explicitly considered in the generated molecules, which is inevitable in targeted-oriented molecules. This paper proposes a framework based on Feedback Generative Adversarial Network (GAN) that includes optimization strategy by incorporating Encoder-Decoder, GAN, and Predictor deep models interconnected with a feedback loop. The Encoder-Decoder converts the string notations of molecules into latent space vectors, effectively creating a new type of molecular representation. At the same time, the GAN can learn and replicate the training data distribution and, therefore, generate new compounds. The feedback loop is designed to incorporate and evaluate the generated molecules according to the multiobjective desired property at every epoch of training to ensure a steady shift of the generated distribution towards the space of the targeted properties. Moreover, to develop a more precise set of molecules, we also incorporate a multiobjective optimization selection technique based on a non-dominated sorting genetic algorithm. The results demonstrate that the proposed framework can generate realistic, novel molecules that span the chemical space. The proposed Encoder-Decoder model correctly reconstructs 99% of the datasets, including stereochemical information. The model's ability to find uncharted regions of the chemical space was successfully shown by optimizing the unbiased GAN to generate molecules with a high binding affinity to the Kappa Opioid and Adenosine [Formula: see text] receptor. Furthermore, the generated compounds exhibit high internal and external diversity levels 0.88 and 0.94, respectively, and uniqueness.

Project description:BackgroundObservational biomedical studies facilitate a new strategy for large-scale electronic health record (EHR) utilization to support precision medicine. However, data label inaccessibility is an increasingly important issue in clinical prediction, despite the use of synthetic and semisupervised learning from data. Little research has aimed to uncover the underlying graphical structure of EHRs.ObjectiveA network-based generative adversarial semisupervised method is proposed. The objective is to train clinical prediction models on label-deficient EHRs to achieve comparable learning performance to supervised methods.MethodsThree public data sets and one colorectal cancer data set gathered from the Second Affiliated Hospital of Zhejiang University were selected as benchmarks. The proposed models were trained on 5% to 25% labeled data and evaluated on classification metrics against conventional semisupervised and supervised methods. The data quality, model security, and memory scalability were also evaluated.ResultsThe proposed method for semisupervised classification outperforms related semisupervised methods under the same setup, with the average area under the receiver operating characteristics curve (AUC) reaching 0.945, 0.673, 0.611, and 0.588 for the four data sets, respectively, followed by graph-based semisupervised learning (0.450, 0.454, 0.425, and 0.5676, respectively) and label propagation (0.475,0.344, 0.440, and 0.477, respectively). The average classification AUCs with 10% labeled data were 0.929, 0.719, 0.652, and 0.650, respectively, comparable to that of the supervised learning methods logistic regression (0.601, 0.670, 0.731, and 0.710, respectively), support vector machines (0.733, 0.720, 0.720, and 0.721, respectively), and random forests (0.982, 0.750, 0.758, and 0.740, respectively). The concerns regarding the secondary use of data and data security are alleviated by realistic data synthesis and robust privacy preservation.ConclusionsTraining clinical prediction models on label-deficient EHRs is indispensable in data-driven research. The proposed method has great potential to exploit the intrinsic structure of EHRs and achieve comparable learning performance to supervised methods.

Dataset Information

Improving antibody optimization ability of generative adversarial network through large language model.

Publications

Improving antibody optimization ability of generative adversarial network through large language model.

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