Abstract
Genome medicine uses genomic information in the diagnosis of disease and in prescribing treatment. This transdisciplinary field brings together knowledge on the relationships between genetics, pathophysiology and pharmacology. Systems pharmacology aims to understand the actions and adverse effects of drugs by considering targets in the context of the biological networks in which they exist. Genome medicine forms the base on which systems pharmacology can develop. Experimental and computational approaches enable systems pharmacology to obtain holistic, mechanistic information on disease networks and drug responses, and to identify new drug targets and specific drug combinations. Network analyses of interactions involved in pathophysiology and drug response across various scales of organization, from molecular to organismal, will allow the integration of the systems-level understanding of drug action with genome medicine. The interface of the two fields will enable drug discovery for personalized medicine. Here we provide a perspective on the questions and approaches that drive the development of these new interrelated fields.
Highlights
Our knowledge of the mechanisms by which drugs act physiologically advanced radically during the twentieth century
Network analyses of interactions involved in pathophysiology and drug response across various scales of organization, from molecular to organismal, will allow the integration of the systems-level understanding of drug action with genome medicine
The influence and relevance of receptor theory in modern pharmacology is derived from the large number of drugs that target membrane receptors, the majority of which are G protein-coupled receptors (GPCRs)
Summary
Our knowledge of the mechanisms by which drugs act physiologically advanced radically during the twentieth century. Integrating the bottom-up and top-down approaches: network analysis Studies on cellular signaling pathways and networks drive systems pharmacology because they can lead to discoveries that enable new therapeutic interventions These networks are often based on genomic information. Genome medicine and systems pharmacology need to be integrated for defining the genes and proteins involved in drug treatment or drug resistance Such integrated analyses can lead to identification of targets that are likely to synergize with or add to the effect of the drug or therapy. A large-scale study of mitochondrial function identified mitochondrial expression profiles affected by drugs that can cause drug-induced myopathies [75]
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