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Prediction of Probable Major Depressive Disorder in the Taiwan Biobank: An Integrated Machine Learning and Genome-Wide Analysis Approach.

ABSTRACT: In light of recent advancements in machine learning, personalized medicine using predictive algorithms serves as an essential paradigmatic methodology. Our goal was to explore an integrated machine learning and genome-wide analysis approach which targets the prediction of probable major depressive disorder (MDD) using 9828 individuals in the Taiwan Biobank. In our analysis, we reported a genome-wide significant association with probable MDD that has not been previously identified: FBN1 on chromosome 15. Furthermore, we pinpointed 17 single nucleotide polymorphisms (SNPs) which show evidence of both associations with probable MDD and potential roles as expression quantitative trait loci (eQTLs). To predict the status of probable MDD, we established prediction models with random undersampling and synthetic minority oversampling using 17 eQTL SNPs and eight clinical variables. We utilized five state-of-the-art models: logistic ridge regression, support vector machine, C4.5 decision tree, LogitBoost, and random forests. Our data revealed that random forests had the highest performance (area under curve = 0.8905 ± 0.0088; repeated 10-fold cross-validation) among the predictive algorithms to infer complex correlations between biomarkers and probable MDD. Our study suggests that an integrated machine learning and genome-wide analysis approach may offer an advantageous method to establish bioinformatics tools for discriminating MDD patients from healthy controls.

SUBMITTER: Lin E

PROVIDER: S-EPMC8308113 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

Dataset Information

Prediction of Probable Major Depressive Disorder in the Taiwan Biobank: An Integrated Machine Learning and Genome-Wide Analysis Approach.

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