title: Big data to smart data in Alzheimer's disease: The brain health modeling initiative to foster actionable knowledge.
abstract: Massive investment and technological advances in the collection of extensive and longitudinal information on thousands of Alzheimer patients results in large amounts of data. These "big-data" databases can potentially advance CNS research and drug development. However, although necessary, they are not sufficient, and we posit that they must be matched with analytical methods that go beyond retrospective data-driven associations with various clinical phenotypes. Although these empirically derived associations can generate novel and useful hypotheses, they need to be organically integrated in a quantitative understanding of the pathology that can be actionable for drug discovery and development. We argue that mechanism-based modeling and simulation approaches, where existing domain knowledge is formally integrated using complexity science and quantitative systems pharmacology can be combined with data-driven analytics to generate predictive actionable knowledge for drug discovery programs, target validation, and optimization of clinical development.
authors.affiliation: In Silico Biosciences, Inc., Berwyn, PA, USA. Electronic address: Hugo-Geerts@In-Silico-Biosciences.com.
authors.forename: Hugo
authors.initials: H
authors.lastname: Geerts
authors.affiliation: Alzheimer's Drug Discovery Foundation, New York, NY, USA.
authors.forename: Penny A
authors.initials: PA
authors.lastname: Dacks
authors.affiliation: Exploratory Statistics, AbbVie, Souderton, PA, USA.
authors.forename: Viswanath
authors.initials: V
authors.lastname: Devanarayan
authors.affiliation: Orion Bionetworks, Inc., Cambridge MA, USA.
authors.forename: Magali
authors.initials: M
authors.lastname: Haas
authors.affiliation: PAD2020, Potomac, MD, USA.
authors.forename: Zaven S
authors.initials: ZS
authors.lastname: Khachaturian
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, USA.
authors.forename: Mark Forrest
authors.initials: MF
authors.lastname: Gordon
authors.affiliation: VIB Department of Molecular Genetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Stuart
authors.initials: S
authors.lastname: Maudsley
authors.affiliation: C-Path Institute, Tucson, AZ, USA.
authors.forename: Klaus
authors.initials: K
authors.lastname: Romero
authors.affiliation: C-Path Institute, Tucson, AZ, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Stephenson
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D003198:Computer Simulation; D016208:Databases, Factual; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D008959:Models, Neurological
keywords: Alzheimer's dementia; Brain disorders; Complexity theory; Drug discovery and development; Systems biology; Systems pharmacology