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Systems pharmacology and genome medicine: a future perspective.

Wist AD, Berger SI, Iyengar R - Genome Med (2009)

Bottom Line: Genome medicine forms the base on which systems pharmacology can develop.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029, USA.

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.

No MeSH data available.


Related in: MedlinePlus

Multi-scale analyses in systems pharmacology. The top half of the figure is a schematic representation of different scales of organization involved in human pathophysiology and systems pharmacology. Clinical indicators and analyses (left) indicate measurements of various types of blood concentrations, blood pressure, stress and so on; these parameters are available in the electronic medical records of patients. From left to right, the scale becomes smaller, or 'zoomed in'. The human body (or organism) can be analyzed at the levels of organs, tissues, cells (represented here together with tissues) or molecules. Drugs are prescribed and taken at the organismal level but exert their effects by interacting with their target at the molecular level (red arrow). The gradient from white to blue corresponds to the various levels of interaction systems: white represents a clinical setting; blue represents a laboratory setting. Studies in systems pharmacology fully span all levels shown here.
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Figure 2: Multi-scale analyses in systems pharmacology. The top half of the figure is a schematic representation of different scales of organization involved in human pathophysiology and systems pharmacology. Clinical indicators and analyses (left) indicate measurements of various types of blood concentrations, blood pressure, stress and so on; these parameters are available in the electronic medical records of patients. From left to right, the scale becomes smaller, or 'zoomed in'. The human body (or organism) can be analyzed at the levels of organs, tissues, cells (represented here together with tissues) or molecules. Drugs are prescribed and taken at the organismal level but exert their effects by interacting with their target at the molecular level (red arrow). The gradient from white to blue corresponds to the various levels of interaction systems: white represents a clinical setting; blue represents a laboratory setting. Studies in systems pharmacology fully span all levels shown here.

Mentions: Systems pharmacology seeks to develop a global understanding of the interactions between pathophysiology and drug action. To develop such an understanding it is necessary to analyze interactions across and between various scales of organization. The representations of different scales are illustrated in Figure 2. The biological insights gained from multi-scale analyses of physiological processes have been noted previously [28,29]. Analysis of such multi-scale systems requires one to 'zoom' in and out depending on the type of analysis being conducted. During the process of multi-scale analysis (zooming), it is essential that we develop a mechanistic understanding of the relationships across the various levels. Simply correlating structural information or molecular interactions with clinical phenotypes is a good starting point, but it will not yield the ability to predict disease progression or drug treatment outcomes. The type of 'system' to be analyzed can vary depending on the zoom level (Figure 2) of information desired. The system can be considered at the organismal, organ, tissue, cellular or molecular levels. The effects of a drug on pathophysiology that are seen at the organismal level, that is, symptoms or clinical measurements, are zoomed-out observations. These observations usually consist of clinical data, ranging from blood chemistry to measurements reflecting organismal function, such as blood pressure and stress tests, all of which are documented in the electronic medical records of the patient that will aid future computational analyses across scales.


Systems pharmacology and genome medicine: a future perspective.

Wist AD, Berger SI, Iyengar R - Genome Med (2009)

Multi-scale analyses in systems pharmacology. The top half of the figure is a schematic representation of different scales of organization involved in human pathophysiology and systems pharmacology. Clinical indicators and analyses (left) indicate measurements of various types of blood concentrations, blood pressure, stress and so on; these parameters are available in the electronic medical records of patients. From left to right, the scale becomes smaller, or 'zoomed in'. The human body (or organism) can be analyzed at the levels of organs, tissues, cells (represented here together with tissues) or molecules. Drugs are prescribed and taken at the organismal level but exert their effects by interacting with their target at the molecular level (red arrow). The gradient from white to blue corresponds to the various levels of interaction systems: white represents a clinical setting; blue represents a laboratory setting. Studies in systems pharmacology fully span all levels shown here.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2651594&req=5

Figure 2: Multi-scale analyses in systems pharmacology. The top half of the figure is a schematic representation of different scales of organization involved in human pathophysiology and systems pharmacology. Clinical indicators and analyses (left) indicate measurements of various types of blood concentrations, blood pressure, stress and so on; these parameters are available in the electronic medical records of patients. From left to right, the scale becomes smaller, or 'zoomed in'. The human body (or organism) can be analyzed at the levels of organs, tissues, cells (represented here together with tissues) or molecules. Drugs are prescribed and taken at the organismal level but exert their effects by interacting with their target at the molecular level (red arrow). The gradient from white to blue corresponds to the various levels of interaction systems: white represents a clinical setting; blue represents a laboratory setting. Studies in systems pharmacology fully span all levels shown here.
Mentions: Systems pharmacology seeks to develop a global understanding of the interactions between pathophysiology and drug action. To develop such an understanding it is necessary to analyze interactions across and between various scales of organization. The representations of different scales are illustrated in Figure 2. The biological insights gained from multi-scale analyses of physiological processes have been noted previously [28,29]. Analysis of such multi-scale systems requires one to 'zoom' in and out depending on the type of analysis being conducted. During the process of multi-scale analysis (zooming), it is essential that we develop a mechanistic understanding of the relationships across the various levels. Simply correlating structural information or molecular interactions with clinical phenotypes is a good starting point, but it will not yield the ability to predict disease progression or drug treatment outcomes. The type of 'system' to be analyzed can vary depending on the zoom level (Figure 2) of information desired. The system can be considered at the organismal, organ, tissue, cellular or molecular levels. The effects of a drug on pathophysiology that are seen at the organismal level, that is, symptoms or clinical measurements, are zoomed-out observations. These observations usually consist of clinical data, ranging from blood chemistry to measurements reflecting organismal function, such as blood pressure and stress tests, all of which are documented in the electronic medical records of the patient that will aid future computational analyses across scales.

Bottom Line: Genome medicine forms the base on which systems pharmacology can develop.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029, USA.

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.

No MeSH data available.


Related in: MedlinePlus