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SuperFeat:从单细胞 RNA-seq 数据中进行定量特征学习有助于药物再利用。

SuperFeat: Quantitative Feature Learning from Single-cell RNA-seq Data Facilitates Drug Repurposing.

机构信息

State Key Laboratory for Oncogenes and Related Genes, Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai 200127, China.

Department of Laboratory Medicine, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.

出版信息

Genomics Proteomics Bioinformatics. 2024 Sep 13;22(3). doi: 10.1093/gpbjnl/qzae036.

Abstract

In this study, we devised a computational framework called Supervised Feature Learning and Scoring (SuperFeat) which enables the training of a machine learning model and evaluates the canonical cellular statuses/features in pathological tissues that underlie the progression of disease. This framework also enables the identification of potential drugs that target the presumed detrimental cellular features. This framework was constructed on the basis of an artificial neural network with the gene expression profiles serving as input nodes. The training data comprised single-cell RNA sequencing datasets that encompassed the specific cell lineage during the developmental progression of cell features. A few models of the canonical cancer-involved cellular statuses/features were tested by such framework. Finally, we illustrated the drug repurposing pipeline, utilizing the training parameters derived from the adverse cellular statuses/features, which yielded successful validation results both in vitro and in vivo. SuperFeat is accessible at https://github.com/weilin-genomics/rSuperFeat.

摘要

在这项研究中,我们设计了一种名为“监督特征学习和评分”(SuperFeat)的计算框架,该框架可以训练机器学习模型,并评估疾病进展所基于的病理性组织中的典型细胞状态/特征。该框架还可以识别针对假定有害细胞特征的潜在药物。该框架基于具有基因表达谱作为输入节点的人工神经网络构建。训练数据包括单细胞 RNA 测序数据集,这些数据集涵盖了细胞特征发育过程中的特定细胞谱系。通过该框架测试了几种典型的癌症相关细胞状态/特征模型。最后,我们说明了利用源自不良细胞状态/特征的训练参数进行药物再利用的管道,该管道在体外和体内均得到了成功验证。SuperFeat 可在 https://github.com/weilin-genomics/rSuperFeat 上获得。

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