Table 1.

Current DT Application in Precision Medicine and Medical Decision-Making Support.

Target Organ/Disease	Reference (Company, Journal etc.)	Description
Heart [1]	Living Heart Project, Dassault Systèmes	The Living Heart Project is the first DT organ considering all aspects of the heart’s functionality, such as blood flow, mechanics, and electrical impulses. The 3D model of the organ has built with a 2D scan of the heart. The Living Heart Model on the 3DEXPERIENCE platform can be used to create new ways to design and test new devices and drug treatments. For instance, physicians can run hypothetical scenarios like adding a pacemaker or reversing the heart chambers to predict the outcome of treatment on the patient.
Heart [12]	CardioInsight, Medtronic	The CardioInsight Noninvasive 3D Mapping System collects chest electrocardiogram (ECG) signals and combines these signals with computerized tomography (CT) scan data to produce and display simultaneous 3-D cardiac maps. The mapping system enables physicians to characterize abnormal rhythms of the heart through a personalized heart model.
Heart [1]	Siemens Healthineers	Another heart DT has been developed by Siemens Healthineers and used for research purposes by Cardiologists of the Heidelberg University Hospital (HUH) in Germany. Although the first study is still in the data evaluation process, preliminary results are promising. Siemens Healthineers developed the DT model by exploiting a massive database containing more than 250 million annotated images, reports, and operational data. The AI-based DT model enables digital heart design based on patient data with the same conditions of the given patient (size, ejection fraction, and muscle contraction).
Brain [17]	Blue Brain Project, EPFL and Hewlett Packard Enterprise	Hewlett Packard Enterprise, partnering with Ecole Polytechnique Fédérale de Lausannes (EPFL), builds a DT of brain called the Blue Brain Project. The project is one of the sub-projects of the Human Brain Project and aims to build biologically detailed digital reconstructions (computer models) and simulations of the mouse brain. In 2018, researchers published the first 3D cell atlas for the entire mouse brain [22].
Human air-way system [1]	Oklahoma State University’s Computational Biofluidics and Biomechanics Laboratory	Researchers developed a prototype of human DT, named ‘‘virtual human V1.0”, with the high-resolution human respiratory system covering the entire conducting and respiratory zones, lung lobes, and body shell. The project aims to study and increase the success rate of cancer-destroying drugs in targeting tumor-only locations.
Brain aneurysm and surrounding blood vessels [1]	Sim&Cure	Sim&Cure developed a DT to treat aneurysms, which are enlarged blood vessels that can result in clots or strokes. DT of the aneurysm and the surrounding blood vessels (represented by a 3D model) allow brain surgeons to run simulations and understand the interactive relationship between the implant and the aneurysm. Although preliminary trials have shown promising results, further evaluation is required.
Multiple Sclerosis (MS) [9]	Frontiers in Immunology (journal)	Multiple sclerosis, also called the ‘disease of a thousand faces’, has high complexity, multidimensionality, and heterogeneity in disease progression and treatment options among patients. This results in extensive data to study the disease. Human DTs are promising in the case of precision medicine for people with MS (pwMS), allowing healthcare professionals to handle this big data, monitor the patient effectively, and provide more personalized treatment and care.
Viral Infection [23]	Science (journal)	Human DTs can predict the viral infection or immune response of a patient infected with a virus by integrating known human physiology and immunology with population and individual clinical data into AI-based models.
Trauma Management [24]	Journal of Medical Systems (journal)	Trauma management is highly critical among time-dependent pathologies. DTs can participate from the pre-hospital phase, where the physician provides the patient first aid and transfers them to the hospital emergency department, to the operative phase, where the trauma team assists the patient in hospital emergency. Although there is no real implementation yet, a system prototype has been developed.
Diabetes [25]	Diabetes (journal)	Human DT can also participate in diabetes management. California-based start-up Twin Health has applied DTs by modeling patient metabolism. The DT model tracks nutrition, sleep, and step changes and monitors patients’ blood sugar levels, liver function, weight, and more. Ongoing clinical trials show that daily precision nutrition guidance based on a continuous glucose monitoring system (CGM), food intake data, and machine learning algorithms can benefit patients with type 2 diabetes.