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Careful feature selection is key in classification of Alzheimer's disease patients based on whole-genome sequencing data.


ABSTRACT: Despite great increase of the amount of data from genome-wide association studies (GWAS) and whole-genome sequencing (WGS), the genetic background of a partially heritable Alzheimer's disease (AD) is not fully understood yet. Machine learning methods are expected to help researchers in the analysis of the large number of SNPs possibly associated with the disease onset. To date, a number of such approaches were applied to genotype-based classification of AD patients and healthy controls using GWAS data and reported accuracy of 0.65-0.975. However, since the estimated influence of genotype on sporadic AD occurrence is lower than that, these very high classification accuracies may potentially be a result of overfitting. We have explored the possibilities of applying feature selection and classification using random forests to WGS and GWAS data from two datasets. Our results suggest that this approach is prone to overfitting if feature selection is performed before division of data into the training and testing set. Therefore, we recommend avoiding selection of features used to build the model based on data included in the testing set. We suggest that for currently available dataset sizes the expected classifier performance is between 0.55 and 0.7 (AUC) and higher accuracies reported in literature are likely a result of overfitting.

SUBMITTER: Osipowicz M 

PROVIDER: S-EPMC8315124 | biostudies-literature |

REPOSITORIES: biostudies-literature

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