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See detailRevolutionizing medicine in the 21(st) century through systems approaches
Hood, Leroy UL; Balling, Rudi UL; Auffray, Charles

in Biotechnology Journal (2012), 7(8), 937-1054

Personalized medicine is a term for a revolution in medicine that envisions the individual patient as the central focus of healthcare in the future. The term "personalized medicine", however, fails to ... [more ▼]

Personalized medicine is a term for a revolution in medicine that envisions the individual patient as the central focus of healthcare in the future. The term "personalized medicine", however, fails to reflect the enormous dimensionality of this new medicine that will be predictive, preventive, personalized, and participatory-a vision of medicine we have termed P4 medicine. This reflects a paradigm change in how medicine will be practiced that is revolutionary rather than evolutionary. P4 medicine arises from the confluence of a systems approach to medicine and from the digitalization of medicine that creates the large data sets necessary to deal with the complexities of disease. We predict that systems approaches will empower the transition from conventional reactive medical practice to a more proactive P4 medicine focused on wellness, and will reverse the escalating costs of drug development an will have enormous social and economic benefits. Our vision for P4 medicine in 10 years is that each patient will be associated with a virtual data cloud of billions of data points and that we will have the information technology for healthcare to reduce this enormous data dimensionality to simple hypotheses about health and/or disease for each individual. These data will be multi-scale across all levels of biological organization and extremely heterogeneous in type - this enormous amount of data represents a striking signal-to-noise (S/N) challenge. The key to dealing with this S/N challenge is to take a "holistic systems approach" to disease as we will discuss in this article. [less ▲]

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See detailFrom experimental setup to bioinformatics: An RNAi screening platform to identify host factors involved in HIV-1 replication
Boerner, Kathleen; Hermle, Johannes; Sommer, Christoph et al

in Biotechnology Journal (2010), 5(1), 39-49

RNA interference (RNAi) has emerged as a powerful technique for studying loss-of-function phenotypes by specific down-regulation of gene expression, allowing the investigation of virus-host interactions ... [more ▼]

RNA interference (RNAi) has emerged as a powerful technique for studying loss-of-function phenotypes by specific down-regulation of gene expression, allowing the investigation of virus-host interactions by large-scale high-throughput RNAi screens. Here we present a robust and sensitive small interfering RNA screening platform consisting of an experimental setup, single-cell image and statistical analysis as well as bioinformatics. The workflow has been established to elucidate host gene functions exploited by viruses, monitoring both suppression and enhancement of viral replication simultaneously by fluorescence microscopy. The platform comprises a two-stage procedure in which potential host factors are first identified in a primary screen and afterwards re-tested in a validation screen to confirm true positive hits. Subsequent bioinformatics allows the identification of cellular genes participating in metabolic pathways and cellular networks utilised by viruses for efficient infection. Our workflow has been used to investigate host factor usage by the human immunodeficiency virus-1 (HIV-1), but can also be adapted to other viruses. Importantly, we expect that the description of the platform will guide further screening approaches for virus-host interactions. The ViroQuant-Cell Networks RNAi Screening core facility is an integral part of the recently founded BioQuant centre for systems biology at the University of Heidelberg and will provide service to external users in the near future. [less ▲]

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