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The start of the field of integrative mathematical modelling and simulations in the study of human biology and physiology can probably be traced back to three highly influential leaders in the field, Prof. James Bassingthwaighte1, Prof. Peter Hunter2, and Prof. Dennis Noble.3 They laid the foundation for the Physiome project.4 As an interesting historical footnote, the workshop on the design of the Physiome project was actually held in Petrodvoretz, Russia, following the 33rd IUPS World Congress in St Petersburg in 1997. Quoting from the Physiome website, the challenge is described as: “The nursery rhyme analogy belies the vast scope and complexity of the physiome challenge. ‘Physi’ means ‘life’ and ‘ome’ means ‘as a whole’. Major diseases like cancer and neurological and cardiovascular diseases are complex in nature, involving everything from genes to environment, lifestyle and in particular aging. Integrating knowledge of all these different components into robust, reliable computer models will yield enormous medical advances in the shape of new therapies and diagnostic tools. Already, mathematical modelling is being used to make better diagnoses and to design advanced medical devices. Within five years, in silico models (computer simulations) will be used for trialling pharmaceutical drugs as well.” The European Union has substantially invested in the Virtual Physiological Human (VPH), which is a methodological and technological framework that, once established, will enable collaborative investigation of the human body as a single complex system. VPH is not “the supermodel” that will explain all possible aspects of human physiology or pathology. It is a way to share observations, to derive predictive hypotheses from them, and to integrate them into a constantly improving understanding of human physiology and pathology, by regarding it as a single system. The driving forces behind this endeavour were many well-known European scientists who were the authors of two influential roadmaps from 20055 and 20076 that laid the foundation for the VPH. Currently, the VPH is a worldwide effort to develop next-generation computer technologies to integrate all information available, from genetics to medical images to clinical data for each patient, and generate computer models capable of predicting how the health of that patient will evolve under certain conditions. In a TEDx lecture in Sheffield Prof. Viceconti gave an overview of the current state of the VPH.7 The VPH is now a well-established worldwide community, with the VPH institute representing it.8 After the unravelling of the human genome in 2001,9 the hunt for genes related to disease, the hunt for understanding of regulatory pathways involved in disease, and the hunt for targets for drugs to fight disease was on. This is not the place to write anymore on this exciting and highly relevant field, other than that the role of computing, as captured in the word bioinformatics, is obvious and extremely relevant. This relates not only to the models and algorithms used, but also to the huge amounts of genomic and proteomic data collected and stored all around the world. One of the main challenges in the field of Computational Systems Biomedicine is to merge these fields together. The Physiome and Virtual Physiological Human aim to deliver computational modelling frameworks for integrating every level in human biology – one that links genes, proteins, cells and organs to the whole body. Ultimately, the goal of the VPH/Physiome Project is to piece together the complete virtual physiological human: a personalised, 3-D model of an individual’s unique physiological make-up. However, having said that, a fair observation is that linking the molecular level, those of genes and proteins, to models for cells, tissue, etc., has not yet been achieved, albeit the whole community believes that this is an important missing link. The VPH series of conferences offers a platform to present research related to the Physiome/VPH, and more broadly, to research into Computational Systems Biomedicine, as well as applications thereof in clinical settings, towards predictive personalised medicine. The conference contributes to better understanding of health and disease, and the healthy living and ageing.