Integrated Patient Digital and Biomimetic Twins for Precision Medicine: A Perspective.

IF 3.7 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Mark T Miedel, Mark E Schurdak, Andrew M Stern, Alejandro Soto-Gutierrez, Eric von Strobl, Jaideep Behari, D Lansing Taylor
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Abstract

A new paradigm for drug development and patient therapeutic strategies is required, especially for complex, heterogeneous diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). Heterogeneity in MASLD patients is driven by genetics, various comorbidities, gut microbiota composition, lifestyle, environment, and demographics that produce multiple patient disease presentations and outcomes. Existing drug development methods have had limited success for complex, heterogeneous diseases like MASLD where only a fraction of patients respond to specific treatments, prediction of a therapeutic response is not presently possible, and the cost of the new classes of drugs is high. However, it is now possible to generate patient digital twins (PDTs) that are computational models of patients using clinomics and other "omics" data collected from patients to make various predictions, including responses to therapeutics. PDTs are then integrated with patient biomimetic twins (PBTs) that are patient-derived organoids or induced pluripotent stem cells that are then differentiated into the optimal number of organ-specific cells to produce organ experimental models. The PBTs mimic key aspects of the patient's pathophysiology, enabling predictions to be tested. In conclusion, integration of PTDs and PBTs has the potential to create a powerful precision medicine platform, yet there are challenges.

精准医学中整合病人数字和仿生双胞胎:一个视角。
需要一种新的药物开发模式和患者治疗策略,特别是对于复杂的异质疾病,包括代谢功能障碍相关的脂肪变性肝病(MASLD)。MASLD患者的异质性是由遗传学、各种合并症、肠道微生物群组成、生活方式、环境和人口统计学驱动的,这些因素会产生多种患者疾病表现和结果。现有的药物开发方法在复杂的异质性疾病方面取得的成功有限,例如MASLD,其中只有一小部分患者对特定治疗有反应,目前无法预测治疗反应,而且新型药物的成本很高。然而,现在有可能生成患者数字双胞胎(PDTs),这是使用从患者收集的临床组学和其他“组学”数据的患者计算模型,以做出各种预测,包括对治疗的反应。然后将pdt与患者仿生双胞胎(pbt)结合,pbt是患者来源的类器官或诱导多能干细胞,然后分化成最佳数量的器官特异性细胞,以产生器官实验模型。PBTs模拟了患者病理生理学的关键方面,使预测能够得到验证。综上所述,数字双胞胎患者和仿生双胞胎患者的整合有可能创造一个强大的精准医疗平台,但也存在挑战。
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来源期刊
Seminars in liver disease
Seminars in liver disease 医学-胃肠肝病学
CiteScore
8.20
自引率
2.40%
发文量
38
期刊介绍: Seminars in Liver Disease is a quarterly review journal that publishes issues related to the specialties of hepatology and gastroenterology. As the premiere review journal in the field, Seminars in Liver Disease provides in-depth coverage with articles and issues focusing on topics such as cirrhosis, transplantation, vascular and coagulation disorders, cytokines, hepatitis B & C, Nonalcoholic Steatosis Syndromes (NASH), pediatric liver diseases, hepatic stem cells, porphyrias as well as a myriad of other diseases related to the liver. Attention is also given to the latest developments in drug therapy along with treatment and current management techniques. Seminars in Liver Disease publishes commissioned reviews. Unsolicited reviews of an exceptional nature or original articles presenting remarkable results will be considered, but case reports will not be published.
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