title: Bioinformatics Mining and Modeling Methods for the Identification of Disease Mechanisms in Neurodegenerative Disorders.
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).
authors.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.|Rheinische Friedrich-Wilhelms-Universitaet Bonn, University of Bonn, Bonn 53113, Germany. martin.hofmann-apitius@scai.fraunhofer.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Hofmann-Apitius
authors.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.|Science for Life Laboratories, Karolinska Institutet, Stockholm SE-171 77, Sweden. gordon.ball@ki.se.
authors.forename: Gordon
authors.initials: G
authors.lastname: Ball
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 7, avenue des Hauts-Fourneaux, Esch-sur-Alzette L-4362, Luxembourg. stephan.gebel@uni.lu.
authors.forename: Stephan
authors.initials: S
authors.lastname: Gebel
authors.affiliation: Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Institutszentrum Birlinghoven, Sankt Augustin D-53754, Germany. shweta.bagewadi@scai.fraunhofer.de.
authors.forename: Shweta
authors.initials: S
authors.lastname: Bagewadi
authors.affiliation: Institute of Health Informatics, University College London, London NW1 2DA, UK. b.bono@ucl.ac.uk.|Auckland Bioengineering Institute, University of Auckland, Symmonds Street, Auckland 1142, New Zealand. b.bono@ucl.ac.uk.
authors.forename: Bernard
authors.initials: B
authors.lastname: de Bono
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 7, avenue des Hauts-Fourneaux, Esch-sur-Alzette L-4362, Luxembourg. reinhard.schneider@uni.lu.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schneider
authors.affiliation: Translational Bioinformatics, UCB Pharma, 216 Bath Rd, Slough SL1 3WE, UK. matthew.page@ucb.com.
authors.forename: Matt
authors.initials: M
authors.lastname: Page
authors.affiliation: Rheinische Friedrich-Wilhelms-Universitaet Bonn, University of Bonn, Bonn 53113, Germany. alpha.tom.kodamullil@scai.fraunhofer.de.
authors.forename: Alpha Tom
authors.initials: AT
authors.lastname: Kodamullil
authors.affiliation: Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Institutszentrum Birlinghoven, Sankt Augustin D-53754, Germany. erfan.younesi@scai.fraunhofer.de.
authors.forename: Erfan
authors.initials: E
authors.lastname: Younesi
authors.affiliation: Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Institutszentrum Birlinghoven, Sankt Augustin D-53754, Germany. christian.ebeling@scai.fraunhofer.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Ebeling
authors.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.|Science for Life Laboratories, Karolinska Institutet, Stockholm SE-171 77, Sweden. jesper.tegner@ki.se.
authors.forename: Jesper
authors.initials: J
authors.lastname: Tegnér
authors.affiliation: Translational Science Unit, SANOFI Recherche &amp; Développement, 1 Avenue Pierre Brossolette, Chilly-Mazarin Cedex 91385, France. luc.canard@sanofi.com.
authors.forename: Luc
authors.initials: L
authors.lastname: Canard
mesh_terms: D000818:Animals; D019295:Computational Biology; D057225:Data Mining; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D051188:Knowledge Bases; D019636:Neurodegenerative Diseases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
keywords: bioinformatics; data integration; disease models; genetics; graphical models; knowledge-based modeling; mechanism-identification; multiscale; neurodegeneration