How Implementation of Systems Biology into Clinical Trials Accelerates Understanding of Diseases
Identifieur interne : 002986 ( Ncbi/Merge ); précédent : 002985; suivant : 002987How Implementation of Systems Biology into Clinical Trials Accelerates Understanding of Diseases
Auteurs : Bibiana Bielekova [États-Unis] ; Yoram Vodovotz [États-Unis] ; Gary An [États-Unis] ; John Hallenbeck [États-Unis]Source :
- Frontiers in Neurology [ 1664-2295 ] ; 2014.
Abstract
Systems biology comprises a series of concepts and approaches that have been used successfully both to delineate novel biological mechanisms and to drive translational advances. The goal of systems biology is to re-integrate putatively critical elements extracted from multi-modality datasets in order to understand how interactions among multiple components form functional networks at the organism/patient-level, and how dysfunction of these networks underlies a particular disease. Due to the genetic and environmental diversity of human subjects, identification of critical elements related to a particular disease process from cross-sectional studies requires prohibitively large cohorts. Alternatively, implementation of systems biology principles to interventional clinical trials represents a unique opportunity to gain predictive understanding of complex diseases in comparatively small cohorts of patients. This paper reviews systems biology principles applicable to translational research, focusing on lessons from systems approaches to inflammation applied to multiple sclerosis. We suggest that employing systems biology methods in the design and execution of biomarker-supported, proof-of-principle clinical trials provides a singular opportunity to merge therapeutic development with a basic understanding of disease processes. The ultimate goal is to develop predictive computational models of the disease, which will revolutionize diagnostic process and provide mechanistic understanding necessary for personalized therapeutic approaches. Added, biologically meaningful information can be derived from diagnostic tests, if they are interpreted in functional relationships, rather than as independent measurements. Such systems biology based diagnostics will transform disease taxonomies from phenotypical to molecular and will allow physicians to select optimal therapeutic regimens for individual patients.
Url:
DOI: 10.3389/fneur.2014.00102
PubMed: 25018747
PubMed Central: 4073421
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<front><div type="abstract" xml:lang="en"><p>Systems biology comprises a series of concepts and approaches that have been used successfully both to delineate novel biological mechanisms and to drive translational advances. The goal of systems biology is to re-integrate putatively critical elements extracted from multi-modality datasets in order to understand how interactions among multiple components form functional networks at the organism/patient-level, and how dysfunction of these networks underlies a particular disease. Due to the genetic and environmental diversity of human subjects, identification of critical elements related to a particular disease process from cross-sectional studies requires prohibitively large cohorts. Alternatively, implementation of systems biology principles to interventional clinical trials represents a unique opportunity to gain predictive understanding of complex diseases in comparatively small cohorts of patients. This paper reviews systems biology principles applicable to translational research, focusing on lessons from systems approaches to inflammation applied to multiple sclerosis. We suggest that employing systems biology methods in the design and execution of biomarker-supported, proof-of-principle clinical trials provides a singular opportunity to merge therapeutic development with a basic understanding of disease processes. The ultimate goal is to develop predictive computational models of the disease, which will revolutionize diagnostic process and provide mechanistic understanding necessary for personalized therapeutic approaches. Added, biologically meaningful information can be derived from diagnostic tests, if they are interpreted in functional relationships, rather than as independent measurements. Such systems biology based diagnostics will transform disease taxonomies from phenotypical to molecular and will allow physicians to select optimal therapeutic regimens for individual patients.</p>
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<double pmid="25018747"><pmc><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">How Implementation of Systems Biology into Clinical Trials Accelerates Understanding of Diseases</title>
<author><name sortKey="Bielekova, Bibiana" sort="Bielekova, Bibiana" uniqKey="Bielekova B" first="Bibiana" last="Bielekova">Bibiana Bielekova</name>
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,<addr-line>Bethesda, MD</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Center for Human Immunology of the National Institutes of Health</institution>
,<addr-line>Bethesda, MD</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Vodovotz, Yoram" sort="Vodovotz, Yoram" uniqKey="Vodovotz Y" first="Yoram" last="Vodovotz">Yoram Vodovotz</name>
<affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Department of Surgery, University of Pittsburgh</institution>
,<addr-line>Pittsburgh, PA</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Center for Inflammation and Regenerative Modeling, McGowan Institute of Regenerative Medicine</institution>
,<addr-line>Pittsburgh, PA</addr-line>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
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<author><name sortKey="An, Gary" sort="An, Gary" uniqKey="An G" first="Gary" last="An">Gary An</name>
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,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Department of Surgery, Northwestern University</institution>
,<addr-line>Chicago, IL</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hallenbeck, John" sort="Hallenbeck, John" uniqKey="Hallenbeck J" first="John" last="Hallenbeck">John Hallenbeck</name>
<affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Stroke Branch, National Institute of Neurological Disorder and Stroke, National Institutes of Health</institution>
,<addr-line>Bethesda, MD</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">How Implementation of Systems Biology into Clinical Trials Accelerates Understanding of Diseases</title>
<author><name sortKey="Bielekova, Bibiana" sort="Bielekova, Bibiana" uniqKey="Bielekova B" first="Bibiana" last="Bielekova">Bibiana Bielekova</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Neuroimmunological Diseases Unit, National Institute of Neurological Disorder and Stroke, National Institutes of Health</institution>
,<addr-line>Bethesda, MD</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Center for Human Immunology of the National Institutes of Health</institution>
,<addr-line>Bethesda, MD</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Vodovotz, Yoram" sort="Vodovotz, Yoram" uniqKey="Vodovotz Y" first="Yoram" last="Vodovotz">Yoram Vodovotz</name>
<affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Department of Surgery, University of Pittsburgh</institution>
,<addr-line>Pittsburgh, PA</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Center for Inflammation and Regenerative Modeling, McGowan Institute of Regenerative Medicine</institution>
,<addr-line>Pittsburgh, PA</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="An, Gary" sort="An, Gary" uniqKey="An G" first="Gary" last="An">Gary An</name>
<affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Center for Inflammation and Regenerative Modeling, McGowan Institute of Regenerative Medicine</institution>
,<addr-line>Pittsburgh, PA</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Department of Surgery, Northwestern University</institution>
,<addr-line>Chicago, IL</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hallenbeck, John" sort="Hallenbeck, John" uniqKey="Hallenbeck J" first="John" last="Hallenbeck">John Hallenbeck</name>
<affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Stroke Branch, National Institute of Neurological Disorder and Stroke, National Institutes of Health</institution>
,<addr-line>Bethesda, MD</addr-line>
,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Frontiers in Neurology</title>
<idno type="eISSN">1664-2295</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
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<front><div type="abstract" xml:lang="en"><p>Systems biology comprises a series of concepts and approaches that have been used successfully both to delineate novel biological mechanisms and to drive translational advances. The goal of systems biology is to re-integrate putatively critical elements extracted from multi-modality datasets in order to understand how interactions among multiple components form functional networks at the organism/patient-level, and how dysfunction of these networks underlies a particular disease. Due to the genetic and environmental diversity of human subjects, identification of critical elements related to a particular disease process from cross-sectional studies requires prohibitively large cohorts. Alternatively, implementation of systems biology principles to interventional clinical trials represents a unique opportunity to gain predictive understanding of complex diseases in comparatively small cohorts of patients. This paper reviews systems biology principles applicable to translational research, focusing on lessons from systems approaches to inflammation applied to multiple sclerosis. We suggest that employing systems biology methods in the design and execution of biomarker-supported, proof-of-principle clinical trials provides a singular opportunity to merge therapeutic development with a basic understanding of disease processes. The ultimate goal is to develop predictive computational models of the disease, which will revolutionize diagnostic process and provide mechanistic understanding necessary for personalized therapeutic approaches. Added, biologically meaningful information can be derived from diagnostic tests, if they are interpreted in functional relationships, rather than as independent measurements. Such systems biology based diagnostics will transform disease taxonomies from phenotypical to molecular and will allow physicians to select optimal therapeutic regimens for individual patients.</p>
</div>
</front>
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<author><name sortKey="Bartels, J" uniqKey="Bartels J">J Bartels</name>
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<author><name sortKey="Kumar, R" uniqKey="Kumar R">R Kumar</name>
</author>
<author><name sortKey="Constantine, G" uniqKey="Constantine G">G Constantine</name>
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<author><name sortKey="Vodovotz, Y" uniqKey="Vodovotz Y">Y Vodovotz</name>
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<pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">How implementation of systems biology into clinical trials accelerates understanding of diseases.</title>
<author><name sortKey="Bielekova, Bibiana" sort="Bielekova, Bibiana" uniqKey="Bielekova B" first="Bibiana" last="Bielekova">Bibiana Bielekova</name>
<affiliation wicri:level="2"><nlm:affiliation>Neuroimmunological Diseases Unit, National Institute of Neurological Disorder and Stroke, National Institutes of Health , Bethesda, MD , USA ; Center for Human Immunology of the National Institutes of Health , Bethesda, MD , USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Neuroimmunological Diseases Unit, National Institute of Neurological Disorder and Stroke, National Institutes of Health , Bethesda, MD , USA ; Center for Human Immunology of the National Institutes of Health , Bethesda, MD </wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Vodovotz, Yoram" sort="Vodovotz, Yoram" uniqKey="Vodovotz Y" first="Yoram" last="Vodovotz">Yoram Vodovotz</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Surgery, University of Pittsburgh , Pittsburgh, PA , USA ; Center for Inflammation and Regenerative Modeling, McGowan Institute of Regenerative Medicine , Pittsburgh, PA , USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Surgery, University of Pittsburgh , Pittsburgh, PA , USA ; Center for Inflammation and Regenerative Modeling, McGowan Institute of Regenerative Medicine , Pittsburgh, PA </wicri:regionArea>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="An, Gary" sort="An, Gary" uniqKey="An G" first="Gary" last="An">Gary An</name>
<affiliation wicri:level="2"><nlm:affiliation>Center for Inflammation and Regenerative Modeling, McGowan Institute of Regenerative Medicine , Pittsburgh, PA , USA ; Department of Surgery, Northwestern University , Chicago, IL , USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Inflammation and Regenerative Modeling, McGowan Institute of Regenerative Medicine , Pittsburgh, PA , USA ; Department of Surgery, Northwestern University , Chicago, IL </wicri:regionArea>
<placeName><region type="state">Illinois</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hallenbeck, John" sort="Hallenbeck, John" uniqKey="Hallenbeck J" first="John" last="Hallenbeck">John Hallenbeck</name>
<affiliation wicri:level="2"><nlm:affiliation>Stroke Branch, National Institute of Neurological Disorder and Stroke, National Institutes of Health , Bethesda, MD , USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Stroke Branch, National Institute of Neurological Disorder and Stroke, National Institutes of Health , Bethesda, MD </wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
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<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2014">2014</date>
<idno type="RBID">pubmed:25018747</idno>
<idno type="pmid">25018747</idno>
<idno type="doi">10.3389/fneur.2014.00102</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">How implementation of systems biology into clinical trials accelerates understanding of diseases.</title>
<author><name sortKey="Bielekova, Bibiana" sort="Bielekova, Bibiana" uniqKey="Bielekova B" first="Bibiana" last="Bielekova">Bibiana Bielekova</name>
<affiliation wicri:level="2"><nlm:affiliation>Neuroimmunological Diseases Unit, National Institute of Neurological Disorder and Stroke, National Institutes of Health , Bethesda, MD , USA ; Center for Human Immunology of the National Institutes of Health , Bethesda, MD , USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Neuroimmunological Diseases Unit, National Institute of Neurological Disorder and Stroke, National Institutes of Health , Bethesda, MD , USA ; Center for Human Immunology of the National Institutes of Health , Bethesda, MD </wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Vodovotz, Yoram" sort="Vodovotz, Yoram" uniqKey="Vodovotz Y" first="Yoram" last="Vodovotz">Yoram Vodovotz</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Surgery, University of Pittsburgh , Pittsburgh, PA , USA ; Center for Inflammation and Regenerative Modeling, McGowan Institute of Regenerative Medicine , Pittsburgh, PA , USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Surgery, University of Pittsburgh , Pittsburgh, PA , USA ; Center for Inflammation and Regenerative Modeling, McGowan Institute of Regenerative Medicine , Pittsburgh, PA </wicri:regionArea>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="An, Gary" sort="An, Gary" uniqKey="An G" first="Gary" last="An">Gary An</name>
<affiliation wicri:level="2"><nlm:affiliation>Center for Inflammation and Regenerative Modeling, McGowan Institute of Regenerative Medicine , Pittsburgh, PA , USA ; Department of Surgery, Northwestern University , Chicago, IL , USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Inflammation and Regenerative Modeling, McGowan Institute of Regenerative Medicine , Pittsburgh, PA , USA ; Department of Surgery, Northwestern University , Chicago, IL </wicri:regionArea>
<placeName><region type="state">Illinois</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hallenbeck, John" sort="Hallenbeck, John" uniqKey="Hallenbeck J" first="John" last="Hallenbeck">John Hallenbeck</name>
<affiliation wicri:level="2"><nlm:affiliation>Stroke Branch, National Institute of Neurological Disorder and Stroke, National Institutes of Health , Bethesda, MD , USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Stroke Branch, National Institute of Neurological Disorder and Stroke, National Institutes of Health , Bethesda, MD </wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Frontiers in neurology</title>
<idno type="ISSN">1664-2295</idno>
<imprint><date when="2014" type="published">2014</date>
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<front><div type="abstract" xml:lang="en">Systems biology comprises a series of concepts and approaches that have been used successfully both to delineate novel biological mechanisms and to drive translational advances. The goal of systems biology is to re-integrate putatively critical elements extracted from multi-modality datasets in order to understand how interactions among multiple components form functional networks at the organism/patient-level, and how dysfunction of these networks underlies a particular disease. Due to the genetic and environmental diversity of human subjects, identification of critical elements related to a particular disease process from cross-sectional studies requires prohibitively large cohorts. Alternatively, implementation of systems biology principles to interventional clinical trials represents a unique opportunity to gain predictive understanding of complex diseases in comparatively small cohorts of patients. This paper reviews systems biology principles applicable to translational research, focusing on lessons from systems approaches to inflammation applied to multiple sclerosis. We suggest that employing systems biology methods in the design and execution of biomarker-supported, proof-of-principle clinical trials provides a singular opportunity to merge therapeutic development with a basic understanding of disease processes. The ultimate goal is to develop predictive computational models of the disease, which will revolutionize diagnostic process and provide mechanistic understanding necessary for personalized therapeutic approaches. Added, biologically meaningful information can be derived from diagnostic tests, if they are interpreted in functional relationships, rather than as independent measurements. Such systems biology based diagnostics will transform disease taxonomies from phenotypical to molecular and will allow physicians to select optimal therapeutic regimens for individual patients.</div>
</front>
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