Application of artificial neural networks to investigate one-carbon metabolism in Alzheimer's disease and healthy matched individuals

• Published in: PloS one Vol. 8; no. 8; p. e74012
• Main Authors: Coppedè, Fabio, Grossi, Enzo, Buscema, Massimo, Migliore, Lucia
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.08.2013; Public Library of Science (PLoS)
• Subjects: Advertising executives; Aged; Aged, 80 and over; Aging; Algorithms; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer's disease; Artificial neural networks; Carbon; Case-Control Studies; Cognitive ability; Cyanocobalamin; Data processing; Dementia; Dementia disorders; Deoxyribonucleic acid; Disease; Disease control; DNA; DNA biosynthesis; DNA methylation; DNA repair; DNA synthesis; Down syndrome; Enzymes; Evolutionary algorithms; Female; Folic acid; Folic Acid - metabolism; Forecasts and trends; Genes; Genetic polymorphisms; Genome-wide association studies; Genomes; Genomics; Genotypes; Homocysteine; Humans; Insulin; Investigations; Male; Medical research; Metabolic Networks and Pathways; Metabolism; Methylation; Models, Biological; Neural networks; Neural Networks, Computer; Neurodegenerative diseases; Physiological aspects; Predictive control; Reproducibility of Results; Risk analysis; Risk factors; Studies; Variables; Vitamin B; Vitamin B12; Italy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0074012

Folate metabolism, also known as one-carbon metabolism, is required for several cellular processes including DNA synthesis, repair and methylation. Impairments of this pathway have been often linked to Alzheimer's disease (AD). In addition, increasing evidence from large scale case-control studies, genome-wide association studies, and meta-analyses of the literature suggest that polymorphisms of genes involved in one-carbon metabolism influence the levels of folate, homocysteine and vitamin B12, and might be among AD risk factors. We analyzed a dataset of 30 genetic and biochemical variables (folate, homocysteine, vitamin B12, and 27 genotypes generated by nine common biallelic polymorphisms of genes involved in folate metabolism) obtained from 40 late-onset AD patients and 40 matched controls to assess the predictive capacity of Artificial Neural Networks (ANNs) in distinguish consistently these two different conditions and to identify the variables expressing the maximal amount of relevant information to the condition of being affected by dementia of Alzheimer's type. Moreover, we constructed a semantic connectivity map to offer some insight regarding the complex biological connections among the studied variables and the two conditions (being AD or control). TWIST system, an evolutionary algorithm able to remove redundant and noisy information from complex data sets, selected 16 variables that allowed specialized ANNs to discriminate between AD and control subjects with over 90% accuracy. The semantic connectivity map provided important information on the complex biological connections among one-carbon metabolic variables highlighting those most closely linked to the AD condition.