Improving CNV Detection Performance in Microarray Data Using a Machine Learning-Based Approach

Copy number variation (CNV) is a primary source of structural variation in the human genome, leading to several disorders. Therefore, analyzing neonatal CNVs is crucial for managing CNV-related chromosomal disabilities. However, genomic waves can hinder accurate CNV analysis. To mitigate the influences of the waves, we adopted a machine learning approach and developed a new method that uses a modified log R ratio instead of the commonly used log R ratio. Validation results using samples with known CNVs demonstrated the superior performance of our method. We analyzed a total of 16,046 Korean newborn samples using the new method and identified CNVs related to 39 genetic disorders were identified in 342 cases. The most frequently detected CNV-related disorder was Joubert syndrome 4. The accuracy of our method was further confirmed by analyzing a subset of the detected results using NGS and comparing them with our results. The utilization of a genome-wide single nucleotide polymorphism array with wave offset was shown to be a powerful method for identifying CNVs in neonatal cases. The accurate screening and the ability to identify various disease susceptibilities offered by our new method could facilitate the identification of CNV-associated chromosomal disease etiologies.