Barbiero Pietro, Viñas Torné Ramon, Lió Pietro
Department of Computer Science and Technology, University of Cambridge, Cambridge, United Kingdom.
Front Genet. 2021 Sep 16;12:652907. doi: 10.3389/fgene.2021.652907. eCollection 2021.
Modern medicine needs to shift from a wait and react, curative discipline to a preventative, interdisciplinary science aiming at providing personalized, systemic, and precise treatment plans to patients. To this purpose, we propose a "digital twin" of patients modeling the human body as a whole and providing a panoramic view over individuals' conditions. We propose a general framework that composes advanced artificial intelligence (AI) approaches and integrates mathematical modeling in order to provide a panoramic view over current and future pathophysiological conditions. Our modular architecture is based on a graph neural network (GNN) forecasting clinically relevant endpoints (such as blood pressure) and a generative adversarial network (GAN) providing a proof of concept of transcriptomic integrability. We tested our digital twin model on two simulated clinical case studies combining information at organ, tissue, and cellular level. We provided a panoramic overview over current and future patient's conditions by monitoring and forecasting clinically relevant endpoints representing the evolution of patient's vital parameters using the GNN model. We showed how to use the GAN to generate multi-tissue expression data for blood and lung to find associations between cytokines conditioned on the expression of genes in the renin-angiotensin pathway. Our approach was to detect inflammatory cytokines, which are known to have effects on blood pressure and have previously been associated with SARS-CoV-2 infection (e.g., CXCR6, XCL1, and others). The graph representation of a computational patient has potential to solve important technological challenges in integrating multiscale computational modeling with AI. We believe that this work represents a step forward toward next-generation devices for precision and predictive medicine.
现代医学需要从一种等待和应对的治疗学科转变为一种预防性的跨学科科学,旨在为患者提供个性化、系统性和精确的治疗方案。为此,我们提出构建患者的“数字孪生”,将人体作为一个整体进行建模,并提供个体状况的全景视图。我们提出了一个通用框架,该框架结合了先进的人工智能(AI)方法并集成了数学建模,以便提供当前和未来病理生理状况的全景视图。我们的模块化架构基于一个预测临床相关终点(如血压)的图神经网络(GNN)和一个提供转录组可整合性概念验证的生成对抗网络(GAN)。我们在两个模拟临床案例研究中测试了我们的数字孪生模型,这些研究结合了器官、组织和细胞水平的信息。通过使用GNN模型监测和预测代表患者生命参数演变的临床相关终点,我们提供了当前和未来患者状况的全景概述。我们展示了如何使用GAN生成血液和肺部的多组织表达数据,以发现肾素 - 血管紧张素途径中基因表达条件下细胞因子之间的关联。我们的方法是检测已知对血压有影响且先前与SARS-CoV-2感染相关的炎性细胞因子(例如CXCR6、XCL1等)。计算患者的图表示有潜力解决将多尺度计算建模与AI整合中的重要技术挑战。我们相信这项工作代表了朝着精准和预测医学的下一代设备迈出的一步。