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Artificial intelligence for dementia genetics and omics.

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Peer-reviewed

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Abstract

Genetics and omics studies of Alzheimer's disease and other dementia subtypes enhance our understanding of underlying mechanisms and pathways that can be targeted. We identified key remaining challenges: First, can we enhance genetic studies to address missing heritability? Can we identify reproducible omics signatures that differentiate between dementia subtypes? Can high-dimensional omics data identify improved biomarkers? How can genetics inform our understanding of causal status of dementia risk factors? And which biological processes are altered by dementia-related genetic variation? Artificial intelligence (AI) and machine learning approaches give us powerful new tools in helping us to tackle these challenges, and we review possible solutions and examples of best practice. However, their limitations also need to be considered, as well as the need for coordinated multidisciplinary research and diverse deeply phenotyped cohorts. Ultimately AI approaches improve our ability to interrogate genetics and omics data for precision dementia medicine. HIGHLIGHTS: We have identified five key challenges in dementia genetics and omics studies. AI can enable detection of undiscovered patterns in dementia genetics and omics data. Enhanced and more diverse genetics and omics datasets are still needed. Multidisciplinary collaborative efforts using AI can boost dementia research.

Description

Funder: UK DRI Ltd.


Funder: UK Medical Research Council


Funder: Multiple System Atrophy Trust; doi: http://dx.doi.org/10.13039/100013128


Funder: Edmond and Lily Safra Early Career Fellowship Program


Funder: Darby Rimmer Foundation


Funder: NIHR Maudsley Biomedical Research Centre


Funder: Ser Cymru II programme


Funder: National Institutefor Health Research (NIHR)


Funder: National Health and Medical Research Council (NHMRC)

Journal Title

Alzheimers Dement

Conference Name

Journal ISSN

1552-5260
1552-5279

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Publisher

Wiley

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Except where otherwised noted, this item's license is described as Attribution 4.0 International
Sponsorship
Alzheimer's Society (573 (AS-RF-21-017))
British Heart Foundation (RE/18/1/34212)
Medical Research Council (MR/X005674/1)
With thanks to the Deep Dementia Phenotyping (DEMON) Network State of the Science symposium participants (in alphabetical order): Peter Bagshaw, Robin Borchert, Magda Bucholc, James Duce, Charlotte James, David Llewellyn, Donald Lyall, Sarah Marzi, Danielle Newby, Neil Oxtoby, Janice Ranson, Tim Rittman, Nathan Skene, Eugene Tang, Michele Veldsman, Laura Winchester, Zhi Yao. This paper was the product of a DEMON Network state of the science symposium entitled “Harnessing Data Science and AI in Dementia Research” funded by Alzheimer's Research UK. C.B. is supported by Alzheimer's Research UK (ARUK-RF2019B-005) and Multiple System Atrophy Trust. N.S. is supported by the UK Dementia Research Institute which receives its funding from UK DRI Ltd., funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK. N.S. also received funding from a UKRI Future Leaders Fellowship (MR/T04327X/1). E.A. is supported by MRC Skills Development Fellowship (MR/W011581/1) and UKRI Future Leaders Fellowship (MR/W011581/1). L.W. is supported Alzheimer's Research UK. I.F.F. is supported by the National Institute on Aging (RF1AG073593). M.A.N.’s participation in this project was part of a competitive contract awarded to Data Tecnica International LLC by the National Institutes of Health to support open science research. J.H. is supported by the NIH National Institute of Neurological Disorders and Stroke (U54NS123743). S.J.M. is funded by the Edmond and Lily Safra Early Career Fellowship Program and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd., funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK. A.A.K. is funded by ALS Association Milton Safenowitz Research Fellowship (grant number22-PDF-609. DOI:10.52546/pc.gr.150909), The Motor Neurone Disease Association (MNDA) Fellowship (Al Khleifat/Oct21/975-799), The Darby Rimmer Foundation, and The NIHR Maudsley Biomedical Research Centre. E.L.H. is supported by the Alzheimer's Society (AS-RF-21-017) and the Cambridge British Heart Foundation Centre of Research Excellence (RE/18/1/34212). V.G. is supported by Diabetes UK (15/0005250), British Heart Foundation (SP/16/6/32726) and Professor David Matthews Non-Clinical Fellowship from the Diabetes Research and Wellness Foundation (SCA/01/NCF/22). C.S. is supported by the UK Dementia Research Institute (UK DRI) funded by the Medical Research Council (MRC), Alzheimer's Society and Alzheimer's Research UK, and by the Ser Cymru II programme which is part-funded by Cardiff University and the European Regional Development Fund through the Welsh Government. S.K. is supported by a PhD studentship award from Alzheimer's Society, UK (AS-PhD-19b-014) and the Ser Cymru II programme. J.M.R. and D.J.L. are supported by Alzheimer's Research UK and the Alan Turing Institute/Engineering and Physical Sciences Research Council (EP/N510129/1). D.J.L. also receives funding from the Medical Research Council (MR/X005674/1), National Institute for Health Research (NIHR) Applied Research Collaboration South West Peninsula, National Health and Medical Research Council (NHMRC), and National Institute on Aging/National Institutes of Health (RF1AG055654). This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging (NIA), National Institutes of Health, Department of Health and Human Services; project number ZO1 AG000535 and ZIA AG000949, as well as the National Institute of Neurological Disorders and Stroke (NINDS). The views expressed in this publication are those of the authors and not necessarily those of the NIHR, NHS, or UK Department of Health and Social Care. This manuscript was facilitated by the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART), through the AI for Precision Dementia Medicine Professional Interest Area (PIA). The views and opinions expressed by authors in this publication represent those of the authors and do not necessarily reflect those of the PIA membership, ISTAART or the Alzheimer's Association.