One contribution of 25 to a Theme Issue 'The virtual physiological human: integrative approaches to computational biomedicine'. European funding under Framework 7 (FP7) for the virtual physiological human (VPH) project has been in place now for 5 years. The VPH Network of Excellence (NoE) has been set up to help develop common standards, open source software, freely accessible data and model repositories, and various training and dissemination activities for the project. It is also working to coordinate the many clinically targeted projects that have been funded under the FP7 calls. An initial vision for the VPH was defined by the FP6 STEP project in 2006. In 2010, we wrote an assessment of the accomplishments of the first two years of the VPH in which we considered the biomedical science, healthcare and information and communications technology challenges facing the project (Hunter et al.

Abstract. We present a design framework for a sensor-based stroke rehabilitation system for use at home developed through the analysis of data collected from a series of workshops. Participants had a variety of backgrounds and included people living with stroke and health professionals who work with them. Our focus in these workshops was to learn more about the social context around stroke care, to share early project ideas and develop a design framework for developing systems. In this paper we present a detailed analysis of participant responses and use this analysis to draw specific conclusions about the components and configuration that we believe should be in future systems.

Despite the promises made that genomic sequencing would transform therapy by introducing a new era of personalized medicine, relatively few tangible breakthroughs have been made. This has led to the recognition that complex interactions at multiple spatial, temporal, and organizational levels may often combine to produce disease. Understanding this complexity requires that existing and future models are used and interpreted within a framework that incorporates knowledge derived from investigations at multiple levels of biological function. It also requires a computational infrastructure capable of dealing with the vast quantities of data generated by genomic approaches. In this review, we discuss the use of molecular modeling to generate quantitative and qualitative insights at the smallest scales of the systems biology hierarchy, how it can play an important role in the development of a systems understanding of disease and in the application of such knowledge to help discover new therapies and target existing ones on a personal level.

Genomics has made enormous progress in the twelve years since the publication of the first draft human genome sequence, but it has not yet been translated into the clinic. Despite spiralling development costs, the number of new drug registrations is not increasing. One reason for this lies in the genetic complexity of disease. Most diseases involve dysregulation in pathways that involve many genes, and many (including most cancers) are themselves genetically heterogeneous. Systems biology involves the multi-level simulation of physiology, cell biology and biochemistry using complex computational techniques. We show here using case studies in cancer and HIV how such computational models, and particularly models based on individual patient data, can be used for drug design and development, and in the selection of the appropriate treatment for a given patient in the face of resistance mutations. If these techniques are to be adopted in routine clinical practice, clinicians will need better training in modern approaches to the integrated analysis of large-scale heterogeneous data and multi-scale models, while developers will need to provide much more usable tools. Investment in computational infrastructure is needed so that results can be returned on clinically relevant timescales and data warehouses designed with data protection as well as accessibility in mind.

As both the amount of generated biological data and the processing compute power increase, computational experimentation is no longer the exclusivity of bioinformaticians, but it is moving across all biomedical domains. For bioinformatics to realize its translational potential, domain experts need access to user-friendly solutions to navigate, integrate and extract information out of biological databases, as well as to combine tools and data resources in bioinformatics workflows. In this review, we present services that assist biomedical scientists in incorporating bioinformatics tools into their research. We review recent applications of Cytoscape, BioGPS and DAVID for data visualization, integration and functional enrichment. Moreover, we illustrate the use of Taverna, Kepler, GenePattern, and Galaxy as open-access workbenches for bioinformatics workflows. Finally, we mention services that facilitate the integration of biomedical ontologies and bioinformatics tools in computational workflows.