Bioinformatics Mining and Modeling Methods for the Identification of Disease Mechanisms in Neurodegenerative Disorders.
Identifieur interne : 000405 ( PubMed/Checkpoint ); précédent : 000404; suivant : 000406Bioinformatics Mining and Modeling Methods for the Identification of Disease Mechanisms in Neurodegenerative Disorders.
Auteurs : Martin Hofmann-Apitius [Allemagne] ; Gordon Ball [Suède] ; Stephan Gebel [Luxembourg (pays)] ; Shweta Bagewadi [Allemagne] ; Bernard De Bono [Royaume-Uni] ; Reinhard Schneider [Luxembourg (pays)] ; Matt Page [Royaume-Uni] ; Alpha Tom Kodamullil [Allemagne] ; Erfan Younesi [Allemagne] ; Christian Ebeling [Allemagne] ; Jesper Tegnér [Suède] ; Luc Canard [France]Source :
- International journal of molecular sciences [ 1422-0067 ] ; 2015.
English descriptors
- KwdEn :
- MESH :
Abstract
Since the decoding of the Human Genome, techniques from bioinformatics, statistics, and machine learning have been instrumental in uncovering patterns in increasing amounts and types of different data produced by technical profiling technologies applied to clinical samples, animal models, and cellular systems. Yet, progress on unravelling biological mechanisms, causally driving diseases, has been limited, in part due to the inherent complexity of biological systems. Whereas we have witnessed progress in the areas of cancer, cardiovascular and metabolic diseases, the area of neurodegenerative diseases has proved to be very challenging. This is in part because the aetiology of neurodegenerative diseases such as Alzheimer´s disease or Parkinson´s disease is unknown, rendering it very difficult to discern early causal events. Here we describe a panel of bioinformatics and modeling approaches that have recently been developed to identify candidate mechanisms of neurodegenerative diseases based on publicly available data and knowledge. We identify two complementary strategies-data mining techniques using genetic data as a starting point to be further enriched using other data-types, or alternatively to encode prior knowledge about disease mechanisms in a model based framework supporting reasoning and enrichment analysis. Our review illustrates the challenges entailed in integrating heterogeneous, multiscale and multimodal information in the area of neurology in general and neurodegeneration in particular. We conclude, that progress would be accelerated by increasing efforts on performing systematic collection of multiple data-types over time from each individual suffering from neurodegenerative disease. The work presented here has been driven by project AETIONOMY; a project funded in the course of the Innovative Medicines Initiative (IMI); which is a public-private partnership of the European Federation of Pharmaceutical Industry Associations (EFPIA) and the European Commission (EC).
DOI: 10.3390/ijms161226148
PubMed: 26690135
Affiliations:
- Allemagne, France, Luxembourg (pays), Royaume-Uni, Suède
- Angleterre, District de Cologne, Grand Londres, Rhénanie-du-Nord-Westphalie, Île-de-France
- Bonn, Londres, Luxembourg, Sankt Augustin
- University College de Londres, Université du Luxembourg
Links toward previous steps (curation, corpus...)
Links to Exploration step
pubmed:26690135Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Bioinformatics Mining and Modeling Methods for the Identification of Disease Mechanisms in Neurodegenerative Disorders.</title><author><name sortKey="Hofmann Apitius, Martin" sort="Hofmann Apitius, Martin" uniqKey="Hofmann Apitius M" first="Martin" last="Hofmann-Apitius">Martin Hofmann-Apitius</name><affiliation wicri:level="3"><nlm:affiliation>Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Institutszentrum Birlinghoven, Sankt Augustin D-53754, Germany. martin.hofmann-apitius@scai.fraunhofer.de.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Institutszentrum Birlinghoven, Sankt Augustin D-53754</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Sankt Augustin</settlement></placeName></affiliation></author><author><name sortKey="Ball, Gordon" sort="Ball, Gordon" uniqKey="Ball G" first="Gordon" last="Ball">Gordon Ball</name><affiliation wicri:level="1"><nlm:affiliation>Unit of Computational Medicine, Center for Molecular Medicine, Department of Medicine, and Unit of Clinical Epidemiology, Karolinska University Hospital, Stockholm SE-171 77, Sweden. gordon.ball@ki.se.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Unit of Computational Medicine, Center for Molecular Medicine, Department of Medicine, and Unit of Clinical Epidemiology, Karolinska University Hospital, Stockholm SE-171 77</wicri:regionArea><wicri:noRegion>Stockholm SE-171 77</wicri:noRegion></affiliation></author><author><name sortKey="Gebel, Stephan" sort="Gebel, Stephan" uniqKey="Gebel S" first="Stephan" last="Gebel">Stephan Gebel</name><affiliation wicri:level="4"><nlm:affiliation>Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 7, avenue des Hauts-Fourneaux, Esch-sur-Alzette L-4362, Luxembourg. stephan.gebel@uni.lu.</nlm:affiliation><country xml:lang="fr">Luxembourg (pays)</country><wicri:regionArea>Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 7, avenue des Hauts-Fourneaux, Esch-sur-Alzette L-4362</wicri:regionArea><orgName type="university">Université du Luxembourg</orgName><placeName><settlement type="city">Luxembourg</settlement></placeName></affiliation></author><author><name sortKey="Bagewadi, Shweta" sort="Bagewadi, Shweta" uniqKey="Bagewadi S" first="Shweta" last="Bagewadi">Shweta Bagewadi</name><affiliation wicri:level="3"><nlm:affiliation>Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Institutszentrum Birlinghoven, Sankt Augustin D-53754, Germany. shweta.bagewadi@scai.fraunhofer.de.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Institutszentrum Birlinghoven, Sankt Augustin D-53754</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Sankt Augustin</settlement></placeName></affiliation></author><author><name sortKey="De Bono, Bernard" sort="De Bono, Bernard" uniqKey="De Bono B" first="Bernard" last="De Bono">Bernard De Bono</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Health Informatics, University College London, London NW1 2DA, UK. b.bono@ucl.ac.uk.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Health Informatics, University College London, London NW1 2DA</wicri:regionArea><orgName type="university">University College de Londres</orgName><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Schneider, Reinhard" sort="Schneider, Reinhard" uniqKey="Schneider R" first="Reinhard" last="Schneider">Reinhard Schneider</name><affiliation wicri:level="4"><nlm:affiliation>Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 7, avenue des Hauts-Fourneaux, Esch-sur-Alzette L-4362, Luxembourg. reinhard.schneider@uni.lu.</nlm:affiliation><country xml:lang="fr">Luxembourg (pays)</country><wicri:regionArea>Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 7, avenue des Hauts-Fourneaux, Esch-sur-Alzette L-4362</wicri:regionArea><orgName type="university">Université du Luxembourg</orgName><placeName><settlement type="city">Luxembourg</settlement></placeName></affiliation></author><author><name sortKey="Page, Matt" sort="Page, Matt" uniqKey="Page M" first="Matt" last="Page">Matt Page</name><affiliation wicri:level="1"><nlm:affiliation>Translational Bioinformatics, UCB Pharma, 216 Bath Rd, Slough SL1 3WE, UK. matthew.page@ucb.com.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Translational Bioinformatics, UCB Pharma, 216 Bath Rd, Slough SL1 3WE</wicri:regionArea><wicri:noRegion>Slough SL1 3WE</wicri:noRegion></affiliation></author><author><name sortKey="Kodamullil, Alpha Tom" sort="Kodamullil, Alpha Tom" uniqKey="Kodamullil A" first="Alpha Tom" last="Kodamullil">Alpha Tom Kodamullil</name><affiliation wicri:level="3"><nlm:affiliation>Rheinische Friedrich-Wilhelms-Universitaet Bonn, University of Bonn, Bonn 53113, Germany. alpha.tom.kodamullil@scai.fraunhofer.de.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Rheinische Friedrich-Wilhelms-Universitaet Bonn, University of Bonn, Bonn 53113</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Younesi, Erfan" sort="Younesi, Erfan" uniqKey="Younesi E" first="Erfan" last="Younesi">Erfan Younesi</name><affiliation wicri:level="3"><nlm:affiliation>Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Institutszentrum Birlinghoven, Sankt Augustin D-53754, Germany. erfan.younesi@scai.fraunhofer.de.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Institutszentrum Birlinghoven, Sankt Augustin D-53754</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Sankt Augustin</settlement></placeName></affiliation></author><author><name sortKey="Ebeling, Christian" sort="Ebeling, Christian" uniqKey="Ebeling C" first="Christian" last="Ebeling">Christian Ebeling</name><affiliation wicri:level="3"><nlm:affiliation>Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Institutszentrum Birlinghoven, Sankt Augustin D-53754, Germany. christian.ebeling@scai.fraunhofer.de.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Institutszentrum Birlinghoven, Sankt Augustin D-53754</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Sankt Augustin</settlement></placeName></affiliation></author><author><name sortKey="Tegner, Jesper" sort="Tegner, Jesper" uniqKey="Tegner J" first="Jesper" last="Tegnér">Jesper Tegnér</name><affiliation wicri:level="1"><nlm:affiliation>Unit of Computational Medicine, Center for Molecular Medicine, Department of Medicine, and Unit of Clinical Epidemiology, Karolinska University Hospital, Stockholm SE-171 77, Sweden. jesper.tegner@ki.se.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Unit of Computational Medicine, Center for Molecular Medicine, Department of Medicine, and Unit of Clinical Epidemiology, Karolinska University Hospital, Stockholm SE-171 77</wicri:regionArea><wicri:noRegion>Stockholm SE-171 77</wicri:noRegion></affiliation></author><author><name sortKey="Canard, Luc" sort="Canard, Luc" uniqKey="Canard L" first="Luc" last="Canard">Luc Canard</name><affiliation wicri:level="3"><nlm:affiliation>Translational Science Unit, SANOFI Recherche & Développement, 1 Avenue Pierre Brossolette, Chilly-Mazarin Cedex 91385, France. luc.canard@sanofi.com.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Translational Science Unit, SANOFI Recherche & Développement, 1 Avenue Pierre Brossolette, Chilly-Mazarin Cedex 91385</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:26690135</idno><idno type="pmid">26690135</idno><idno type="doi">10.3390/ijms161226148</idno><idno type="wicri:Area/PubMed/Corpus">000240</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000240</idno><idno type="wicri:Area/PubMed/Curation">000239</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000239</idno><idno type="wicri:Area/PubMed/Checkpoint">000239</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000239</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Bioinformatics Mining and Modeling Methods for the Identification of Disease Mechanisms in Neurodegenerative Disorders.</title><author><name sortKey="Hofmann Apitius, Martin" sort="Hofmann Apitius, Martin" uniqKey="Hofmann Apitius M" first="Martin" last="Hofmann-Apitius">Martin Hofmann-Apitius</name><affiliation wicri:level="3"><nlm:affiliation>Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Institutszentrum Birlinghoven, Sankt Augustin D-53754, Germany. martin.hofmann-apitius@scai.fraunhofer.de.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Institutszentrum Birlinghoven, Sankt Augustin D-53754</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Sankt Augustin</settlement></placeName></affiliation></author><author><name sortKey="Ball, Gordon" sort="Ball, Gordon" uniqKey="Ball G" first="Gordon" last="Ball">Gordon Ball</name><affiliation wicri:level="1"><nlm:affiliation>Unit of Computational Medicine, Center for Molecular Medicine, Department of Medicine, and Unit of Clinical Epidemiology, Karolinska University Hospital, Stockholm SE-171 77, Sweden. gordon.ball@ki.se.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Unit of Computational Medicine, Center for Molecular Medicine, Department of Medicine, and Unit of Clinical Epidemiology, Karolinska University Hospital, Stockholm SE-171 77</wicri:regionArea><wicri:noRegion>Stockholm SE-171 77</wicri:noRegion></affiliation></author><author><name sortKey="Gebel, Stephan" sort="Gebel, Stephan" uniqKey="Gebel S" first="Stephan" last="Gebel">Stephan Gebel</name><affiliation wicri:level="4"><nlm:affiliation>Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 7, avenue des Hauts-Fourneaux, Esch-sur-Alzette L-4362, Luxembourg. stephan.gebel@uni.lu.</nlm:affiliation><country xml:lang="fr">Luxembourg (pays)</country><wicri:regionArea>Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 7, avenue des Hauts-Fourneaux, Esch-sur-Alzette L-4362</wicri:regionArea><orgName type="university">Université du Luxembourg</orgName><placeName><settlement type="city">Luxembourg</settlement></placeName></affiliation></author><author><name sortKey="Bagewadi, Shweta" sort="Bagewadi, Shweta" uniqKey="Bagewadi S" first="Shweta" last="Bagewadi">Shweta Bagewadi</name><affiliation wicri:level="3"><nlm:affiliation>Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Institutszentrum Birlinghoven, Sankt Augustin D-53754, Germany. shweta.bagewadi@scai.fraunhofer.de.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Institutszentrum Birlinghoven, Sankt Augustin D-53754</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Sankt Augustin</settlement></placeName></affiliation></author><author><name sortKey="De Bono, Bernard" sort="De Bono, Bernard" uniqKey="De Bono B" first="Bernard" last="De Bono">Bernard De Bono</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Health Informatics, University College London, London NW1 2DA, UK. b.bono@ucl.ac.uk.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Health Informatics, University College London, London NW1 2DA</wicri:regionArea><orgName type="university">University College de Londres</orgName><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Schneider, Reinhard" sort="Schneider, Reinhard" uniqKey="Schneider R" first="Reinhard" last="Schneider">Reinhard Schneider</name><affiliation wicri:level="4"><nlm:affiliation>Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 7, avenue des Hauts-Fourneaux, Esch-sur-Alzette L-4362, Luxembourg. reinhard.schneider@uni.lu.</nlm:affiliation><country xml:lang="fr">Luxembourg (pays)</country><wicri:regionArea>Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 7, avenue des Hauts-Fourneaux, Esch-sur-Alzette L-4362</wicri:regionArea><orgName type="university">Université du Luxembourg</orgName><placeName><settlement type="city">Luxembourg</settlement></placeName></affiliation></author><author><name sortKey="Page, Matt" sort="Page, Matt" uniqKey="Page M" first="Matt" last="Page">Matt Page</name><affiliation wicri:level="1"><nlm:affiliation>Translational Bioinformatics, UCB Pharma, 216 Bath Rd, Slough SL1 3WE, UK. matthew.page@ucb.com.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Translational Bioinformatics, UCB Pharma, 216 Bath Rd, Slough SL1 3WE</wicri:regionArea><wicri:noRegion>Slough SL1 3WE</wicri:noRegion></affiliation></author><author><name sortKey="Kodamullil, Alpha Tom" sort="Kodamullil, Alpha Tom" uniqKey="Kodamullil A" first="Alpha Tom" last="Kodamullil">Alpha Tom Kodamullil</name><affiliation wicri:level="3"><nlm:affiliation>Rheinische Friedrich-Wilhelms-Universitaet Bonn, University of Bonn, Bonn 53113, Germany. alpha.tom.kodamullil@scai.fraunhofer.de.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Rheinische Friedrich-Wilhelms-Universitaet Bonn, University of Bonn, Bonn 53113</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Younesi, Erfan" sort="Younesi, Erfan" uniqKey="Younesi E" first="Erfan" last="Younesi">Erfan Younesi</name><affiliation wicri:level="3"><nlm:affiliation>Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Institutszentrum Birlinghoven, Sankt Augustin D-53754, Germany. erfan.younesi@scai.fraunhofer.de.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Institutszentrum Birlinghoven, Sankt Augustin D-53754</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Sankt Augustin</settlement></placeName></affiliation></author><author><name sortKey="Ebeling, Christian" sort="Ebeling, Christian" uniqKey="Ebeling C" first="Christian" last="Ebeling">Christian Ebeling</name><affiliation wicri:level="3"><nlm:affiliation>Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Institutszentrum Birlinghoven, Sankt Augustin D-53754, Germany. christian.ebeling@scai.fraunhofer.de.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Institutszentrum Birlinghoven, Sankt Augustin D-53754</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Sankt Augustin</settlement></placeName></affiliation></author><author><name sortKey="Tegner, Jesper" sort="Tegner, Jesper" uniqKey="Tegner J" first="Jesper" last="Tegnér">Jesper Tegnér</name><affiliation wicri:level="1"><nlm:affiliation>Unit of Computational Medicine, Center for Molecular Medicine, Department of Medicine, and Unit of Clinical Epidemiology, Karolinska University Hospital, Stockholm SE-171 77, Sweden. jesper.tegner@ki.se.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Unit of Computational Medicine, Center for Molecular Medicine, Department of Medicine, and Unit of Clinical Epidemiology, Karolinska University Hospital, Stockholm SE-171 77</wicri:regionArea><wicri:noRegion>Stockholm SE-171 77</wicri:noRegion></affiliation></author><author><name sortKey="Canard, Luc" sort="Canard, Luc" uniqKey="Canard L" first="Luc" last="Canard">Luc Canard</name><affiliation wicri:level="3"><nlm:affiliation>Translational Science Unit, SANOFI Recherche & Développement, 1 Avenue Pierre Brossolette, Chilly-Mazarin Cedex 91385, France. luc.canard@sanofi.com.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Translational Science Unit, SANOFI Recherche & Développement, 1 Avenue Pierre Brossolette, Chilly-Mazarin Cedex 91385</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author></analytic><series><title level="j">International journal of molecular sciences</title><idno type="eISSN">1422-0067</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Computational Biology</term><term>Data Mining</term><term>Genetic Predisposition to Disease</term><term>Genome-Wide Association Study</term><term>Humans</term><term>Knowledge Bases</term><term>Neurodegenerative Diseases (genetics)</term><term>Polymorphism, Single Nucleotide</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Neurodegenerative Diseases</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Computational Biology</term><term>Data Mining</term><term>Genetic Predisposition to Disease</term><term>Genome-Wide Association Study</term><term>Humans</term><term>Knowledge Bases</term><term>Polymorphism, Single Nucleotide</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Since the decoding of the Human Genome, techniques from bioinformatics, statistics, and machine learning have been instrumental in uncovering patterns in increasing amounts and types of different data produced by technical profiling technologies applied to clinical samples, animal models, and cellular systems. Yet, progress on unravelling biological mechanisms, causally driving diseases, has been limited, in part due to the inherent complexity of biological systems. Whereas we have witnessed progress in the areas of cancer, cardiovascular and metabolic diseases, the area of neurodegenerative diseases has proved to be very challenging. This is in part because the aetiology of neurodegenerative diseases such as Alzheimer´s disease or Parkinson´s disease is unknown, rendering it very difficult to discern early causal events. Here we describe a panel of bioinformatics and modeling approaches that have recently been developed to identify candidate mechanisms of neurodegenerative diseases based on publicly available data and knowledge. We identify two complementary strategies-data mining techniques using genetic data as a starting point to be further enriched using other data-types, or alternatively to encode prior knowledge about disease mechanisms in a model based framework supporting reasoning and enrichment analysis. Our review illustrates the challenges entailed in integrating heterogeneous, multiscale and multimodal information in the area of neurology in general and neurodegeneration in particular. We conclude, that progress would be accelerated by increasing efforts on performing systematic collection of multiple data-types over time from each individual suffering from neurodegenerative disease. The work presented here has been driven by project AETIONOMY; a project funded in the course of the Innovative Medicines Initiative (IMI); which is a public-private partnership of the European Federation of Pharmaceutical Industry Associations (EFPIA) and the European Commission (EC).</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26690135</PMID><DateCreated><Year>2015</Year><Month>12</Month><Day>22</Day></DateCreated><DateCompleted><Year>2016</Year><Month>09</Month><Day>26</Day></DateCompleted><DateRevised><Year>2016</Year><Month>01</Month><Day>07</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1422-0067</ISSN><JournalIssue CitedMedium="Internet"><Volume>16</Volume><Issue>12</Issue><PubDate><Year>2015</Year><Month>Dec</Month><Day>07</Day></PubDate></JournalIssue><Title>International journal of molecular sciences</Title><ISOAbbreviation>Int J Mol Sci</ISOAbbreviation></Journal><ArticleTitle>Bioinformatics Mining and Modeling Methods for the Identification of Disease Mechanisms in Neurodegenerative Disorders.</ArticleTitle><Pagination><MedlinePgn>29179-206</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.3390/ijms161226148</ELocationID><Abstract><AbstractText>Since the decoding of the Human Genome, techniques from bioinformatics, statistics, and machine learning have been instrumental in uncovering patterns in increasing amounts and types of different data produced by technical profiling technologies applied to clinical samples, animal models, and cellular systems. Yet, progress on unravelling biological mechanisms, causally driving diseases, has been limited, in part due to the inherent complexity of biological systems. Whereas we have witnessed progress in the areas of cancer, cardiovascular and metabolic diseases, the area of neurodegenerative diseases has proved to be very challenging. This is in part because the aetiology of neurodegenerative diseases such as Alzheimer´s disease or Parkinson´s disease is unknown, rendering it very difficult to discern early causal events. Here we describe a panel of bioinformatics and modeling approaches that have recently been developed to identify candidate mechanisms of neurodegenerative diseases based on publicly available data and knowledge. We identify two complementary strategies-data mining techniques using genetic data as a starting point to be further enriched using other data-types, or alternatively to encode prior knowledge about disease mechanisms in a model based framework supporting reasoning and enrichment analysis. Our review illustrates the challenges entailed in integrating heterogeneous, multiscale and multimodal information in the area of neurology in general and neurodegeneration in particular. We conclude, that progress would be accelerated by increasing efforts on performing systematic collection of multiple data-types over time from each individual suffering from neurodegenerative disease. The work presented here has been driven by project AETIONOMY; a project funded in the course of the Innovative Medicines Initiative (IMI); which is a public-private partnership of the European Federation of Pharmaceutical Industry Associations (EFPIA) and the European Commission (EC).</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Hofmann-Apitius</LastName><ForeName>Martin</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Institutszentrum Birlinghoven, Sankt Augustin D-53754, Germany. martin.hofmann-apitius@scai.fraunhofer.de.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Rheinische Friedrich-Wilhelms-Universitaet Bonn, University of Bonn, Bonn 53113, Germany. martin.hofmann-apitius@scai.fraunhofer.de.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ball</LastName><ForeName>Gordon</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Unit of Computational Medicine, Center for Molecular Medicine, Department of Medicine, and Unit of Clinical Epidemiology, Karolinska University Hospital, Stockholm SE-171 77, Sweden. gordon.ball@ki.se.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Science for Life Laboratories, Karolinska Institutet, Stockholm SE-171 77, Sweden. gordon.ball@ki.se.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gebel</LastName><ForeName>Stephan</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 7, avenue des Hauts-Fourneaux, Esch-sur-Alzette L-4362, Luxembourg. stephan.gebel@uni.lu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bagewadi</LastName><ForeName>Shweta</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Institutszentrum Birlinghoven, Sankt Augustin D-53754, Germany. shweta.bagewadi@scai.fraunhofer.de.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>de Bono</LastName><ForeName>Bernard</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Institute of Health Informatics, University College London, London NW1 2DA, UK. b.bono@ucl.ac.uk.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Auckland Bioengineering Institute, University of Auckland, Symmonds Street, Auckland 1142, New Zealand. b.bono@ucl.ac.uk.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schneider</LastName><ForeName>Reinhard</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 7, avenue des Hauts-Fourneaux, Esch-sur-Alzette L-4362, Luxembourg. reinhard.schneider@uni.lu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Page</LastName><ForeName>Matt</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Translational Bioinformatics, UCB Pharma, 216 Bath Rd, Slough SL1 3WE, UK. matthew.page@ucb.com.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kodamullil</LastName><ForeName>Alpha Tom</ForeName><Initials>AT</Initials><AffiliationInfo><Affiliation>Rheinische Friedrich-Wilhelms-Universitaet Bonn, University of Bonn, Bonn 53113, Germany. alpha.tom.kodamullil@scai.fraunhofer.de.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Younesi</LastName><ForeName>Erfan</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Institutszentrum Birlinghoven, Sankt Augustin D-53754, Germany. erfan.younesi@scai.fraunhofer.de.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ebeling</LastName><ForeName>Christian</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Institutszentrum Birlinghoven, Sankt Augustin D-53754, Germany. christian.ebeling@scai.fraunhofer.de.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tegnér</LastName><ForeName>Jesper</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Unit of Computational Medicine, Center for Molecular Medicine, Department of Medicine, and Unit of Clinical Epidemiology, Karolinska University Hospital, Stockholm SE-171 77, Sweden. jesper.tegner@ki.se.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Science for Life Laboratories, Karolinska Institutet, Stockholm SE-171 77, Sweden. jesper.tegner@ki.se.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Canard</LastName><ForeName>Luc</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Translational Science Unit, SANOFI Recherche & Développement, 1 Avenue Pierre Brossolette, Chilly-Mazarin Cedex 91385, France. luc.canard@sanofi.com.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>12</Month><Day>07</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Int J Mol Sci</MedlineTA><NlmUniqueID>101092791</NlmUniqueID><ISSNLinking>1422-0067</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Bioinformatics. 2012 Apr 15;28(8):1114-21</RefSource><PMID Version="1">22355083</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>PLoS One. 2012;7(4):e35012</RefSource><PMID Version="1">22514701</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Hum Mutat. 2012 May;33(5):837-48</RefSource><PMID Version="1">22616108</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nat Rev Neurol. 2012 Aug;8(8):451-64</RefSource><PMID Version="1">22801974</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Cold Spring Harb Perspect Med. 2012;2(8). pii: a006239. doi: 10.1101/cshperspect.a006239</RefSource><PMID Version="1">22908189</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>N Engl J Med. 2012 Aug 30;367(9):795-804</RefSource><PMID Version="1">22784036</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Environ Health Perspect. 2003 May;111(6):793-5</RefSource><PMID Version="1">12760826</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Genome Res. 2003 Nov;13(11):2498-504</RefSource><PMID Version="1">14597658</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nucleic Acids Res. 2004 Jan 1;32(Database issue):D452-5</RefSource><PMID Version="1">14681455</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nature. 1998 Apr 9;392(6676):605-8</RefSource><PMID Version="1">9560156</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50</RefSource><PMID Version="1">16199517</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Neuroimaging Clin N Am. 2005 Nov;15(4):869-77, xi-xii</RefSource><PMID Version="1">16443497</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Science. 2006 Sep 29;313(5795):1960-4</RefSource><PMID Version="1">17008531</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nucleic Acids Res. 2007 Jan;35(Database issue):D572-4</RefSource><PMID Version="1">17135203</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>BMC Syst Biol. 2007;1:37</RefSource><PMID Version="1">17683609</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nucleic Acids Res. 2008 Jan;36(Database issue):D344-50</RefSource><PMID Version="1">17932057</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Biomed Inform. 2008 Oct;41(5):706-16</RefSource><PMID Version="1">18472304</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nature. 2009 Feb 19;457(7232):1012-4</RefSource><PMID Version="1">19020500</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>BMC Syst Biol. 2009;3:56</RefSource><PMID Version="1">19497118</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nature. 2009 Sep 10;461(7261):218-23</RefSource><PMID Version="1">19741703</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nature. 2011 May 5;473(7345):43-9</RefSource><PMID Version="1">21441907</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Biochim Biophys Acta. 2010 Jan;1802(1):2-10</RefSource><PMID Version="1">19853658</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Sci Transl Med. 2010 Oct 6;2(52):52ra73</RefSource><PMID Version="1">20926834</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nat Biotechnol. 2010 Oct;28(10):1045-8</RefSource><PMID Version="1">20944595</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Comput Biol. 2011 Mar;18(3):507-22</RefSource><PMID Version="1">21385051</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Curr Neurol Neurosci Rep. 2011 Jun;11(3):246-53</RefSource><PMID Version="1">21487954</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Neurosci Res. 2011 Jun;89(6):808-14</RefSource><PMID Version="1">21374699</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Cold Spring Harb Perspect Med. 2012 Oct;2(10). pii: a006296. doi: 10.1101/cshperspect.a006296</RefSource><PMID Version="1">23028126</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Drug Discov Today. 2012 Nov;17(21-22):1188-98</RefSource><PMID Version="1">22683805</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Lancet Neurol. 2013 Jan;12(1):92-104</RefSource><PMID Version="1">23237904</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nucleic Acids Res. 2013 Jan;41(Database issue):D991-5</RefSource><PMID Version="1">23193258</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Lancet Neurol. 2013 Feb;12(2):207-16</RefSource><PMID Version="1">23332364</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nat Biotechnol. 2013 May;31(5):419-25</RefSource><PMID Version="1">23455439</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nat Rev Neurosci. 2011 Dec;12(12):723-38</RefSource><PMID Version="1">22048062</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nature. 2013 Oct 17;502(7471):333-9</RefSource><PMID Version="1">24132290</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Toxicol Appl Pharmacol. 2013 Nov 1;272(3):863-78</RefSource><PMID Version="1">23933166</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nat Genet. 2013 Dec;45(12):1452-8</RefSource><PMID Version="1">24162737</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Sci Rep. 2013;3:3375</RefSource><PMID Version="1">24287435</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>BMC Bioinformatics. 2013;14:340</RefSource><PMID Version="1">24266983</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nat Rev Genet. 2014 Jan;15(1):34-48</RefSource><PMID Version="1">24296534</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Toxicol Sci. 2014 Jan;137(1):234-48</RefSource><PMID Version="1">24136188</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nucleic Acids Res. 2014 Jan;42(Database issue):D1091-7</RefSource><PMID Version="1">24203711</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nucleic Acids Res. 2014 Jan;42(Database issue):D472-7</RefSource><PMID Version="1">24243840</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Mol Neurobiol. 2014 Feb;49(1):88-102</RefSource><PMID Version="1">23832570</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Sci Signal. 2014 Feb 18;7(313):ra17</RefSource><PMID Version="1">24550542</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Drug Discov Today. 2014 Feb;19(2):193-8</RefSource><PMID Version="1">24444544</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Alzheimers Dement. 2014 Mar;10(2):238-46</RefSource><PMID Version="1">23830913</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Brain Imaging Behav. 2014 Jun;8(2):153-82</RefSource><PMID Version="1">24399358</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nat Commun. 2014;5:3887</RefSource><PMID Version="1">24871328</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nat Rev Immunol. 2014 Jul;14(7):463-77</RefSource><PMID Version="1">24962261</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>BMC Syst Biol. 2014;8 Suppl 2:I1</RefSource><PMID Version="1">25032990</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Trends Pharmacol Sci. 2014 Sep;35(9):450-60</RefSource><PMID Version="1">25109570</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Cell. 2014 Dec 4;159(6):1461-75</RefSource><PMID Version="1">25433701</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Biol Psychiatry. 2015 Jan 1;77(1):43-51</RefSource><PMID Version="1">24951455</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nat Rev Genet. 2015 Feb;16(2):85-97</RefSource><PMID Version="1">25582081</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nucleic Acids Res. 2015 Jan;43(Database issue):D204-12</RefSource><PMID Version="1">25348405</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nucleic Acids Res. 2015 Jan;43(Database issue):D447-52</RefSource><PMID Version="1">25352553</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nucleic Acids Res. 2015 Jan;43(Database issue):D1079-85</RefSource><PMID Version="1">25361968</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nucleic Acids Res. 2015 Jan;43(Database issue):D1113-6</RefSource><PMID Version="1">25361974</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nucleic Acids Res. 2015 Jan;43(Database issue):D470-8</RefSource><PMID Version="1">25428363</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nucleic Acids Res. 2015 Jan;43(Database issue):D213-21</RefSource><PMID Version="1">25428371</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Science. 2015 Jan 23;347(6220):1260419</RefSource><PMID Version="1">25613900</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nat Genet. 2015 Feb;47(2):106-14</RefSource><PMID Version="1">25501392</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nat Rev Drug Discov. 2015 Feb;14(2):75-6</RefSource><PMID Version="1">25633780</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>CNS Neurol Disord Drug Targets. 2014;13(10):1654-66</RefSource><PMID Version="1">25470401</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Neurobiol Dis. 2015 Feb;74:1-13</RefSource><PMID Version="1">25447234</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>PLoS One. 2015;10(2):e0116718</RefSource><PMID Version="1">25665127</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Cell Death Dis. 2015;6:e1708</RefSource><PMID Version="1">25837484</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Brief Bioinform. 2015 May;16(3):393-412</RefSource><PMID Version="1">24916300</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Alzheimers Dement. 2015 Jul;11(7):792-814</RefSource><PMID Version="1">26194313</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Theor Biol Med Model. 2015;12:20</RefSource><PMID Version="1">26395080</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Database (Oxford). 2015;2015. pii: bav099. doi: 10.1093/database/bav099</RefSource><PMID Version="1">26475471</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Alzheimers Dement. 2015 Nov;11(11):1329-39</RefSource><PMID Version="1">25849034</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nucleic Acids Res. 2016 Jan 4;44(D1):D488-94</RefSource><PMID Version="1">26481357</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Brief Bioinform. 2016 May;17(3):505-16</RefSource><PMID Version="1">26249223</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nature. 1999 Dec 2;402(6761 Suppl):C47-52</RefSource><PMID Version="1">10591225</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Clin Pharmacol Ther. 2001 Mar;69(3):89-95</RefSource><PMID Version="1">11240971</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nucleic Acids Res. 2011 Jul;39(Web Server issue):W541-5</RefSource><PMID Version="1">21672956</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nat Rev Drug Discov. 2011 Sep;10(9):641-2</RefSource><PMID Version="1">21878965</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>PLoS Comput Biol. 2011 Sep;7(9):e1002180</RefSource><PMID Version="1">21980275</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Physiol Rev. 2011 Oct;91(4):1161-218</RefSource><PMID Version="1">22013209</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Adv Exp Med Biol. 2012;736:645-53</RefSource><PMID Version="1">22161357</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nucleic Acids Res. 2012 Jan;40(Database issue):D930-4</RefSource><PMID Version="1">22064851</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Bioinformatics. 2012 Feb 1;28(3):448-50</RefSource><PMID Version="1">22130590</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Cell. 2012 Mar 16;148(6):1204-22</RefSource><PMID Version="1">22424230</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019295" MajorTopicYN="N">Computational Biology</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D057225" MajorTopicYN="Y">Data Mining</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020022" MajorTopicYN="N">Genetic Predisposition to Disease</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D055106" MajorTopicYN="N">Genome-Wide Association Study</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051188" MajorTopicYN="N">Knowledge Bases</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019636" MajorTopicYN="N">Neurodegenerative Diseases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020641" MajorTopicYN="N">Polymorphism, Single Nucleotide</DescriptorName></MeshHeading></MeshHeadingList><OtherID Source="NLM">PMC4691095</OtherID><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">bioinformatics</Keyword><Keyword MajorTopicYN="N">data integration</Keyword><Keyword MajorTopicYN="N">disease models</Keyword><Keyword MajorTopicYN="N">genetics</Keyword><Keyword MajorTopicYN="N">graphical models</Keyword><Keyword MajorTopicYN="N">knowledge-based modeling</Keyword><Keyword MajorTopicYN="N">mechanism-identification</Keyword><Keyword MajorTopicYN="N">multiscale</Keyword><Keyword MajorTopicYN="N">neurodegeneration</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2015</Year><Month>10</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2015</Year><Month>11</Month><Day>10</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2015</Year><Month>11</Month><Day>12</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2015</Year><Month>12</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2015</Year><Month>12</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2016</Year><Month>9</Month><Day>27</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">26690135</ArticleId><ArticleId IdType="pii">ijms161226148</ArticleId><ArticleId IdType="doi">10.3390/ijms161226148</ArticleId><ArticleId IdType="pmc">PMC4691095</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Allemagne</li><li>France</li><li>Luxembourg (pays)</li><li>Royaume-Uni</li><li>Suède</li></country><region><li>Angleterre</li><li>District de Cologne</li><li>Grand Londres</li><li>Rhénanie-du-Nord-Westphalie</li><li>Île-de-France</li></region><settlement><li>Bonn</li><li>Londres</li><li>Luxembourg</li><li>Sankt Augustin</li></settlement><orgName><li>University College de Londres</li><li>Université du Luxembourg</li></orgName></list><tree><country name="Allemagne"><region name="Rhénanie-du-Nord-Westphalie"><name sortKey="Hofmann Apitius, Martin" sort="Hofmann Apitius, Martin" uniqKey="Hofmann Apitius M" first="Martin" last="Hofmann-Apitius">Martin Hofmann-Apitius</name></region><name sortKey="Bagewadi, Shweta" sort="Bagewadi, Shweta" uniqKey="Bagewadi S" first="Shweta" last="Bagewadi">Shweta Bagewadi</name><name sortKey="Ebeling, Christian" sort="Ebeling, Christian" uniqKey="Ebeling C" first="Christian" last="Ebeling">Christian Ebeling</name><name sortKey="Kodamullil, Alpha Tom" sort="Kodamullil, Alpha Tom" uniqKey="Kodamullil A" first="Alpha Tom" last="Kodamullil">Alpha Tom Kodamullil</name><name sortKey="Younesi, Erfan" sort="Younesi, Erfan" uniqKey="Younesi E" first="Erfan" last="Younesi">Erfan Younesi</name></country><country name="Suède"><noRegion><name sortKey="Ball, Gordon" sort="Ball, Gordon" uniqKey="Ball G" first="Gordon" last="Ball">Gordon Ball</name></noRegion><name sortKey="Tegner, Jesper" sort="Tegner, Jesper" uniqKey="Tegner J" first="Jesper" last="Tegnér">Jesper Tegnér</name></country><country name="Luxembourg (pays)"><noRegion><name sortKey="Gebel, Stephan" sort="Gebel, Stephan" uniqKey="Gebel S" first="Stephan" last="Gebel">Stephan Gebel</name></noRegion><name sortKey="Schneider, Reinhard" sort="Schneider, Reinhard" uniqKey="Schneider R" first="Reinhard" last="Schneider">Reinhard Schneider</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="De Bono, Bernard" sort="De Bono, Bernard" uniqKey="De Bono B" first="Bernard" last="De Bono">Bernard De Bono</name></region><name sortKey="Page, Matt" sort="Page, Matt" uniqKey="Page M" first="Matt" last="Page">Matt Page</name></country><country name="France"><region name="Île-de-France"><name sortKey="Canard, Luc" sort="Canard, Luc" uniqKey="Canard L" first="Luc" last="Canard">Luc Canard</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonFranceV1/Data/PubMed/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000405 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PubMed/Checkpoint/biblio.hfd -nk 000405 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonFranceV1
|flux= PubMed
|étape= Checkpoint
|type= RBID
|clé= pubmed:26690135
|texte= Bioinformatics Mining and Modeling Methods for the Identification of Disease Mechanisms in Neurodegenerative Disorders.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Checkpoint/RBID.i -Sk "pubmed:26690135" \
| HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Checkpoint/biblio.hfd \
| NlmPubMed2Wicri -a ParkinsonFranceV1
| This area was generated with Dilib version V0.6.29. |  |