CNVind: an open source cloud-based pipeline for rare CNVs detection in whole exome sequencing data based on the depth of coverage

BACKGROUND: A typical Copy Number Variations (CNVs) detection process based on the depth of coverage in the Whole Exome Sequencing (WES) data consists of several steps: (I) calculating the depth of coverage in sequencing regions, (II) quality control, (III) normalizing the depth of coverage, (IV) calling CNVs. Previous tools performed one normalization process for each chromosome—all the coverage depths in the sequencing regions from a given chromosome were normalized in a single run. METHODS: Herein, we present the new CNVind tool for calling CNVs, where the normalization process is conducted separately for each of the sequencing regions. The total number of normalizations is equal to the number of sequencing regions in the investigated dataset. For example, when analyzing a dataset composed of n sequencing regions, CNVind performs n independent depth of coverage normalizations. Before each normalization, the application selects the k most correlated sequencing regions with the depth of coverage Pearson’s Correlation as distance metric. Then, the resulting subgroup of [Formula: see text] sequencing regions is normalized, the results of all n independent normalizations are combined; finally, the segmentation and CNV calling process is performed on the resultant dataset. RESULTS AND CONCLUSIONS: We used WES data from the 1000 Genomes project to evaluate the impact of independent normalization on CNV calling performance and compared the results with state-of-the-art tools: CODEX and exomeCopy. The results proved that independent normalization allows to improve the rare CNVs detection specificity significantly. For example, for the investigated dataset, we reduced the number of FP calls from over 15,000 to around 5000 while maintaining a constant number of TP calls equal to about 150 CNVs. However, independent normalization of each sequencing region is a computationally expensive process, therefore our pipeline is customized and can be easily run in the cloud computing environment, on the computer cluster, or the single CPU server. To our knowledge, the presented application is the first attempt to implement an innovative approach to independent normalization of the depth of WES data coverage. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12859-022-04617-x.