Journal article
Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference
Nature communications, Vol.9(1), 4273
10/15/2018
DOI: 10.1038/s41467-018-05892-0
PMCID: PMC6189176
PMID: 30323170
Abstract
The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique-Subtype and Stage Inference (SuStaIn)-able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer's disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18 × 10
) or temporal stage (p = 3.96 × 10
). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine.
Details
- Title: Subtitle
- Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference
- Creators
- Alexandra L Young - Department of Computer Science, University College London, London, WC1E 6BT, UK. alexandra.young@ucl.ac.ukRazvan V Marinescu - Department of Computer Science, University College London, London, WC1E 6BT, UKNeil P Oxtoby - Department of Computer Science, University College London, London, WC1E 6BT, UKMartina Bocchetta - Dementia Research Centre, Institute of Neurology, University College London, London, WC1N 3BG, UKKeir Yong - Dementia Research Centre, Institute of Neurology, University College London, London, WC1N 3BG, UKNicholas C Firth - Department of Computer Science, University College London, London, WC1E 6BT, UKDavid M Cash - Dementia Research Centre, Institute of Neurology, University College London, London, WC1N 3BG, UKDavid L Thomas - Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, University College London, London, WC1N 3BG, UKKatrina M Dick - Dementia Research Centre, Institute of Neurology, University College London, London, WC1N 3BG, UKJorge Cardoso - School of Biomedical Engineering and Imaging Sciences, King's College London, London, WC2R 2LS, UKJohn van Swieten - Erasmus Medical Center, 3000 CA, Rotterdam, The NetherlandsBarbara Borroni - Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, 25121, Brescia, ItalyDaniela Galimberti - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, via F. Sforza, 35, 20122, Milan, ItalyMario Masellis - Sunnybrook Health Sciences Centre, University of Toronto, ON, M4N 3M5, CanadaMaria Carmela Tartaglia - Centre for Research in Neurodegenerative Diseases, University of Toronto, ON, Toronto, M5T 0S8, CanadaJames B Rowe - University of Cambridge, Department of Clinical Neurosciences, Cambridge, CB2 0SZ, UKCaroline Graff - Karolinska Institutet, 171 77, Solna, SwedenFabrizio Tagliavini - Istituto Neurologico Carlo Besta, 20133, Milan, ItalyGiovanni B Frisoni - University Hospitals and University of Geneva, Geneva, SwitzerlandRobert Laforce Jr - Université Laval, Quebec, QC, G1V 0A6, CanadaElizabeth Finger - University of Western Ontario, London, ON, N6A 3K7, CanadaAlexandre de Mendonça - Faculdade de Medicina, Universidade de Lisboa, 1649-028, Lisboa, PortugalSandro Sorbi - IRCCS Fondazione Don Carlo Gnocchi, Florence, ItalyJason D Warren - Dementia Research Centre, Institute of Neurology, University College London, London, WC1N 3BG, UKSebastian Crutch - Dementia Research Centre, Institute of Neurology, University College London, London, WC1N 3BG, UKNick C Fox - Dementia Research Centre, Institute of Neurology, University College London, London, WC1N 3BG, UKSebastien Ourselin - School of Biomedical Engineering and Imaging Sciences, King's College London, London, WC2R 2LS, UKJonathan M Schott - Dementia Research Centre, Institute of Neurology, University College London, London, WC1N 3BG, UKJonathan D Rohrer - Dementia Research Centre, Institute of Neurology, University College London, London, WC1N 3BG, UKDaniel C Alexander - Department of Computer Science, University College London, London, WC1E 6BT, UKGenetic FTD Initiative (GENFI)Alzheimer’s Disease Neuroimaging Initiative (ADNI)
- Contributors
- Laura L Boles-Ponto (Contributor) - University of Iowa, Radiology
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.9(1), 4273
- DOI
- 10.1038/s41467-018-05892-0
- PMID
- 30323170
- PMCID
- PMC6189176
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Publisher
- England
- Grant note
- MR/J009482/1 / Medical Research Council MR/M023664/1 / Medical Research Council Wellcome Trust MC_U105597119 / Medical Research Council MR/M009041/1 / Medical Research Council MR/M008525/1 / Medical Research Council MC_UU_00005/12 / Medical Research Council P30 AG010129 / NIA NIH HHS U01 AG024904 / NIA NIH HHS MC_UU_00024/1 / Medical Research Council MR/M009106/1 / Medical Research Council
- Language
- English
- Date published
- 10/15/2018
- Academic Unit
- Radiology; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984051598002771
Metrics
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