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诊疗基因组

The Theranostic Genome.

作者信息

Xu Xiaoying, Jané Pablo, Taelman Vincent, Jané Eduardo, Dumont Rebecca A, Garama Yonathan, Kim Francisco, Del Val Gómez María, Gariani Karim, Walter Martin A

机构信息

University of Lucerne, Lucerne, LU, Switzerland.

University of Geneva, Geneva, GE, Switzerland.

出版信息

Nat Commun. 2024 Dec 30;15(1):10904. doi: 10.1038/s41467-024-55291-x.

Abstract

Theranostic drugs represent an emerging path to deliver on the promise of precision medicine. However, bottlenecks remain in characterizing theranostic targets, identifying theranostic lead compounds, and tailoring theranostic drugs. To overcome these bottlenecks, we present the Theranostic Genome, the part of the human genome whose expression can be utilized to combine therapeutic and diagnostic applications. Using a deep learning-based hybrid human-AI pipeline that cross-references PubMed, the Gene Expression Omnibus, DisGeNET, The Cancer Genome Atlas and the NIH Molecular Imaging and Contrast Agent Database, we bridge individual genes in human cancers with respective theranostic compounds. Cross-referencing the Theranostic Genome with RNAseq data from over 17'000 human tissues identifies theranostic targets and lead compounds for various human cancers, and allows tailoring targeted theranostics to relevant cancer subpopulations. We expect the Theranostic Genome to facilitate the development of new targeted theranostics to better diagnose, understand, treat, and monitor a variety of human cancers.

摘要

治疗诊断药物代表了实现精准医学前景的一条新兴途径。然而,在表征治疗诊断靶点、确定治疗诊断先导化合物以及定制治疗诊断药物方面仍然存在瓶颈。为了克服这些瓶颈,我们提出了治疗诊断基因组,即人类基因组中其表达可用于结合治疗和诊断应用的部分。通过使用基于深度学习的人机混合人工智能管道,该管道对PubMed、基因表达综合数据库(Gene Expression Omnibus)、疾病基因网络(DisGeNET)、癌症基因组图谱(The Cancer Genome Atlas)和美国国立卫生研究院分子成像与造影剂数据库(NIH Molecular Imaging and Contrast Agent Database)进行交叉引用,我们将人类癌症中的单个基因与相应的治疗诊断化合物联系起来。将治疗诊断基因组与来自超过17000个人类组织的RNA测序数据进行交叉引用,可识别各种人类癌症的治疗诊断靶点和先导化合物,并能够针对相关癌症亚群定制靶向治疗诊断方法。我们期望治疗诊断基因组能够促进新型靶向治疗诊断方法的开发,以更好地诊断、理解、治疗和监测各种人类癌症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ac6/11686231/9976c781627f/41467_2024_55291_Fig1_HTML.jpg

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