Alzheimer's disease biomarker discovery using in silico literature mining and clinical validation

Journal of Translational Medicine

Research

Magda Tsolaki¹  Christian Spenger²  Lars-Olof Wahlund³  Patrizia Mecocci⁴  Joanna Riddoch-Contreras⁵  Andrew Simmons⁵  Simon Lovestone⁵  Ines Greco⁵  Iwona Kłoszewska⁶  Bruno Vellas⁷  Hilkka Soininen⁸  Jane Reed⁹  Nicola Day⁹  Julie Barnes^1,10 

[1] 3rd Department of Neurology, "G. Papanicolaou" Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece;Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden;Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden;Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy;King’s College London, Institute of Psychiatry, De Crespigny Park, SE5 8AF, London, UK;Medical University of Lodz, Lodz, Poland;UMR INSERM 1027, Gerontopole, CHU Toulouse, University of Toulouse, Toulouse, France;University of Eastern Finland and University Hospital of Kuopio, Kuopio, Finland;now Instem Scientific, BioWisdom Ltd, Cambridge, UK;now Instem Scientific, BioWisdom Ltd, Cambridge, UK;Currently at Somaxa Ltd and Abcodia Ltd, London, UK;

关键词: Alzheimer’s disease;    Proteomics;    Biomarkers;    Choline acetyltransferase (ChAt);    Urokinase-type plasminogen activator receptor (PLAUR);    Intelligence network;    Bioinformatics;    MRI;    in silico;    Literature mining;   

DOI  :  10.1186/1479-5876-10-217

 received in 2012-03-28, accepted in 2012-09-14,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundAlzheimer’s Disease (AD) is the most widespread form of dementia in the elderly but despite progress made in recent years towards a mechanistic understanding, there is still an urgent need for disease modification therapy and for early diagnostic tests. Substantial international efforts are being made to discover and validate biomarkers for AD using candidate analytes and various data-driven 'omics' approaches. Cerebrospinal fluid is in many ways the tissue of choice for biomarkers of brain disease but is limited by patient and clinician acceptability, and increasing attention is being paid to the search for blood-based biomarkers. The aim of this study was to use a novel in silico approach to discover a set of candidate biomarkers for AD.MethodsWe used an in silico literature mining approach to identify potential biomarkers by creating a summarized set of assertional metadata derived from relevant legacy information. We then assessed the validity of this approach using direct assays of the identified biomarkers in plasma by immunodetection methods.ResultsUsing this in silico approach, we identified 25 biomarker candidates, at least three of which have subsequently been reported to be altered in blood or CSF from AD patients. Two further candidate biomarkers, indicated from the in silico approach, were choline acetyltransferase and urokinase-type plasminogen activator receptor. Using immunodetection, we showed that, in a large sample set, these markers are either altered in disease or correlate with MRI markers of atrophy.ConclusionsThese data support as a proof of concept the use of data mining and in silico analyses to derive valid biomarker candidates for AD and, by extension, for other disorders.

【 授权许可】

Unknown   
© Greco et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.