How Implementation of Systems Biology into Clinical Trials Accelerates Understanding of Diseases
Identifieur interne : 001F17 ( Pmc/Curation ); précédent : 001F16; suivant : 001F18How 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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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></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><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><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Yankner, Ba" uniqKey="Yankner B">BA Yankner</name></author><author><name sortKey="Lu, T" uniqKey="Lu T">T Lu</name></author><author><name sortKey="Loerch, P" uniqKey="Loerch P">P Loerch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Soto, C" uniqKey="Soto C">C Soto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Confavreux, C" uniqKey="Confavreux C">C Confavreux</name></author><author><name sortKey="Vukusic, S" uniqKey="Vukusic S">S Vukusic</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kirkwood, Tb" uniqKey="Kirkwood T">TB 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Front Neurol</journal-id><journal-id journal-id-type="iso-abbrev">Front Neurol</journal-id><journal-id journal-id-type="publisher-id">Front. Neurol.</journal-id><journal-title-group><journal-title>Frontiers in Neurology</journal-title></journal-title-group><issn pub-type="epub">1664-2295</issn><publisher><publisher-name>Frontiers Media S.A.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25018747</article-id><article-id pub-id-type="pmc">4073421</article-id><article-id pub-id-type="doi">10.3389/fneur.2014.00102</article-id><article-categories><subj-group subj-group-type="heading"><subject>Neuroscience</subject><subj-group><subject>Review Article</subject></subj-group></subj-group></article-categories><title-group><article-title>How Implementation of Systems Biology into Clinical Trials Accelerates Understanding of Diseases</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Bielekova</surname><given-names>Bibiana</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="corresp" rid="cor1">*</xref><uri xlink:type="simple" xlink:href="http://frontiersin.org/people/u/147850"></uri></contrib><contrib contrib-type="author"><name><surname>Vodovotz</surname><given-names>Yoram</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><xref ref-type="aff" rid="aff4"><sup>4</sup></xref><uri xlink:type="simple" xlink:href="http://frontiersin.org/people/u/44682"></uri></contrib><contrib contrib-type="author"><name><surname>An</surname><given-names>Gary</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref><xref ref-type="aff" rid="aff5"><sup>5</sup></xref><uri xlink:type="simple" xlink:href="http://frontiersin.org/people/u/42993"></uri></contrib><contrib contrib-type="author"><name><surname>Hallenbeck</surname><given-names>John</given-names></name><xref ref-type="aff" rid="aff6"><sup>6</sup></xref></contrib></contrib-group><aff id="aff1"><sup>1</sup><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></aff><aff id="aff2"><sup>2</sup><institution>Center for Human Immunology of the National Institutes of Health</institution>,<addr-line>Bethesda, MD</addr-line>,<country>USA</country></aff><aff id="aff3"><sup>3</sup><institution>Department of Surgery, University of Pittsburgh</institution>,<addr-line>Pittsburgh, PA</addr-line>,<country>USA</country></aff><aff id="aff4"><sup>4</sup><institution>Center for Inflammation and Regenerative Modeling, McGowan Institute of Regenerative Medicine</institution>,<addr-line>Pittsburgh, PA</addr-line>,<country>USA</country></aff><aff id="aff5"><sup>5</sup><institution>Department of Surgery, Northwestern University</institution>,<addr-line>Chicago, IL</addr-line>,<country>USA</country></aff><aff id="aff6"><sup>6</sup><institution>Stroke Branch, National Institute of Neurological Disorder and Stroke, National Institutes of Health</institution>,<addr-line>Bethesda, MD</addr-line>,<country>USA</country></aff><author-notes><fn fn-type="edited-by"><p>Edited by: Amy Lovett-Racke, The Ohio State University, USA</p></fn><fn fn-type="edited-by"><p>Reviewed by: Nancy Monson, University of Texas Southwestern Medical Center, USA; Marie Csete, Huntington Medical Research Institutes, USA</p></fn><corresp content-type="corresp" id="cor1">*Correspondence: Bibiana Bielekova, NIH/NINDS/NIB, Bld10/R, 5C103, 10 Center Drive, MSC1400, Bethesda, MD 20892, USA e-mail: <email>bibi.bielekova@nih.gov</email></corresp><fn fn-type="other" id="fn001"><p>This article was submitted to Multiple Sclerosis and Neuroimmunology, a section of the journal Frontiers in Neurology.</p></fn></author-notes><pub-date pub-type="epub"><day>27</day><month>6</month><year>2014</year></pub-date><pub-date pub-type="collection"><year>2014</year></pub-date><volume>5</volume><elocation-id>102</elocation-id><history><date date-type="received"><day>28</day><month>3</month><year>2014</year></date><date date-type="accepted"><day>05</day><month>6</month><year>2014</year></date></history><permissions><copyright-statement>Copyright © 2014 Bielekova, Vodovotz, An and Hallenbeck.</copyright-statement><copyright-year>2014</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/3.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p></license></permissions><abstract><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></abstract><kwd-group><kwd>systems biology</kwd><kwd>clinical trials</kwd><kwd>clinical trials methodology</kwd><kwd>multiple sclerosis</kwd><kwd>polygenic diseases</kwd></kwd-group><counts><fig-count count="3"></fig-count><table-count count="0"></table-count><equation-count count="0"></equation-count><ref-count count="60"></ref-count><page-count count="9"></page-count><word-count count="8146"></word-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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