An adaptive genetic algorithm for selection of blood-based biomarkers for prediction of Alzheimer's disease progression

Conference name: Joint 26th Genome Informatics Workshop and Asia Pacific Bioinformatics Network (APBioNet) 14th International Conference on Bioinformatics (GIW/InCoB2015)

Conference date: 9-11 September 2015

Keywords: adaptive genetic algorithm, logistic regression, Alzheimer's, biomarkers, prediction

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Abstract

Background

Alzheimer's disease is a multifactorial disorder that may be diagnosed earlier using a combination of tests rather than any single test. Search algorithms and optimization techniques in combination with model evaluation techniques have been used previously to perform the selection of suitable feature sets. Previously we successfully applied GA with LR to neuropsychological data contained within the The Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, to select cognitive tests for prediction of progression of AD. This research addresses an Adaptive Genetic Algorithm (AGA) in combination with LR for identifying the best biomarker combination for prediction of the progression to AD.

Results

The model has been explored in terms of parameter optimization to predict conversion from healthy stage to AD with high accuracy. Several feature sets were selected - the resulting prediction moddels showed higher area under the ROC values (0.83-0.89). The results has shown consistency with some of the medical research reported in literature.

Conclusion

The AGA has proven useful in selecting the best combination of biomarkers for prediction of AD progression. The algorithm presented here is generic and can be extended to other data sets generated in projects that seek to identify combination of biomarkers or other features that are predictive of disease onset or progression.

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Most cited references 8

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Measuring the accuracy of diagnostic systems.

J Swets (1988)

Diagnostic systems of several kinds are used to distinguish between two classes of events, essentially "signals" and "noise". For them, analysis in terms of the "relative operating characteristic" of signal detection theory provides a precise and valid measure of diagnostic accuracy. It is the only measure available that is uninfluenced by decision biases and prior probabilities, and it places the performances of diverse systems on a common, easily interpreted scale. Representative values of this measure are reported here for systems in medical imaging, materials testing, weather forecasting, information retrieval, polygraph lie detection, and aptitude testing. Though the measure itself is sound, the values obtained from tests of diagnostic systems often require qualification because the test data on which they are based are of unsure quality. A common set of problems in testing is faced in all fields. How well these problems are handled, or can be handled in a given field, determines the degree of confidence that can be placed in a measured value of accuracy. Some fields fare much better than others.

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Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease.

R. Clarke, A. D. Smith, K A Jobst … (1998)

Recent studies suggest that vascular disease may contribute to the cause of Alzheimer disease (AD). Since elevated plasma total homocysteine (tHcy) level is a risk factor for vascular disease, it may also be relevant to AD. To examine the association of AD with blood levels of tHcy, and its biological determinants folate and vitamin B12. Case-control study of 164 patients, aged 55 years or older, with a clinical diagnosis of dementia of Alzheimer type (DAT), including 76 patients with histologically confirmed AD and 108 control subjects. Referral population to a hospital clinic between July 1988 and April 1996. Serum tHcy, folate, and vitamin B12 levels in patients and controls at entry; the odds ratio of DAT or confirmed AD with elevated tHcy or low vitamin levels; and the rate of disease progression in relation to tHcy levels at entry. Serum tHcy levels were significantly higher and serum folate and vitamin B12 levels were lower in patients with DAT and patients with histologically confirmed AD than in controls. The odds ratio of confirmed AD associated with a tHcy level in the top third (> or = 14 micromol/L) compared with the bottom third (< or = 11 micromol/L) of the control distribution was 4.5 (95% confidence interval, 2.2-9.2), after adjustment for age, sex, social class, cigarette smoking, and apolipoprotein E epsilon4. The corresponding odds ratio for the lower third compared with the upper third of serum folate distribution was 3.3 (95% confidence interval, 1.8-6.3) and of vitamin B12 distribution was 4.3 (95% confidence interval, 2.1-8.8). The mean tHcy levels were unaltered by duration of symptoms before enrollment and were stable for several years afterward. In a 3-year follow-up of patients with DAT, radiological evidence of disease progression was greater among those with higher tHcy levels at entry. Low blood levels of folate and vitamin B12, and elevated tHcy levels were associated with AD. The stability of tHcy levels over time and lack of relationship with duration of symptoms argue against these findings being a consequence of disease and warrant further studies to assess the clinical relevance of these associations for AD.

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Genetic Evidence Implicates the Immune System and Cholesterol Metabolism in the Aetiology of Alzheimer's Disease

Lesley Jones, Peter A. Holmans, Marian Hamshere … (2010)

Background Late Onset Alzheimer's disease (LOAD) is the leading cause of dementia. Recent large genome-wide association studies (GWAS) identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes. Methodology We applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset. Principal Findings We found a significant overrepresentation of association signals in pathways related to cholesterol metabolism and the immune response in both of the two largest genome-wide association studies for LOAD. Significance Processes related to cholesterol metabolism and the innate immune response have previously been implicated by pathological and epidemiological studies of Alzheimer's disease, but it has been unclear whether those findings reflected primary aetiological events or consequences of the disease process. Our independent evidence from two large studies now demonstrates that these processes are aetiologically relevant, and suggests that they may be suitable targets for novel and existing therapeutic approaches.

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Author and article information

Contributors

Luke Vandewater

Vladimir Brusic

William Wilson

Lance Macaulay

Ping Zhang

Conference

Journal ID (nlm-ta): BMC Bioinformatics

Journal ID (iso-abbrev): BMC Bioinformatics

Title: BMC Bioinformatics

Publisher: BioMed Central

ISSN (Electronic): 1471-2105

Publication date Collection: 2015

Publication date (Electronic): 9 December 2015

Volume: 16

Issue: Suppl 18

Page: S1

Affiliations

[1 ]Digital Productivity Flagship, CSIRO, Australia

[2 ]School of Medicine and Bioinformatics Center, Nazarbayev University, Kazakhstan

[3 ]Food and Nutrition Flagship, CSIRO, Australia

[4 ]Menzies Health Institute Queensland, Griffith University, Australia

Article

Publisher ID: 1471-2105-16-S18-S1

DOI: 10.1186/1471-2105-16-S18-S1

PMC ID: 4682419

PubMed ID: 26680269

SO-VID: 349f0b9e-3b2c-4e58-9614-524c5ef17c67

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Conference name: Joint 26th Genome Informatics Workshop and Asia Pacific Bioinformatics Network (APBioNet) 14th International Conference on Bioinformatics (GIW/InCoB2015)

An adaptive genetic algorithm for selection of blood-based biomarkers for prediction of Alzheimer's disease progression

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Abstract

Background

Results

Conclusion

Related collections

Alternative approaches to Alzheimer's Disease

Most cited references 8

Measuring the accuracy of diagnostic systems.

Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease.

Genetic Evidence Implicates the Immune System and Cholesterol Metabolism in the Aetiology of Alzheimer's Disease

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