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Open Access Highly Accessed Research article

Identification of recurrent regions of copy-number variants across multiple individuals

Teo Shu Mei125, Agus Salim12, Stefano Calza3, Ku Chee Seng2, Chia Kee Seng12 and Yudi Pawitan4*

Author Affiliations

1 Department of Epidemiology and Public Health, National University of Singapore, 16 Medical Drive, 117597, Singapore

2 Centre for Molecular Epidemiology, National University of Singapore, 30 Biopolis Street, 138671, Singapore

3 Department of Biomedical Sciences and Biotechnology, University of Brescia, Viale Europa, 11 25123 Brescia, Italy

4 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, Stockholm 17177, Sweden

5 NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 28 Medical Drive, 117456, Singapore

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BMC Bioinformatics 2010, 11:147  doi:10.1186/1471-2105-11-147

Published: 22 March 2010



Algorithms and software for CNV detection have been developed, but they detect the CNV regions sample-by-sample with individual-specific breakpoints, while common CNV regions are likely to occur at the same genomic locations across different individuals in a homogenous population. Current algorithms to detect common CNV regions do not account for the varying reliability of the individual CNVs, typically reported as confidence scores by SNP-based CNV detection algorithms. General methodologies for identifying these recurrent regions, especially those directed at SNP arrays, are still needed.


In this paper, we describe two new approaches for identifying common CNV regions based on (i) the frequency of occurrence of reliable CNVs, where reliability is determined by high confidence scores, and (ii) a weighted frequency of occurrence of CNVs, where the weights are determined by the confidence scores. In addition, motivated by the fact that we often observe partially overlapping CNV regions as a mixture of two or more distinct subregions, regions identified using the two approaches can be fine-tuned to smaller sub-regions using a clustering algorithm. We compared the performance of the methods with sequencing-based results in terms of discordance rates, rates of departure from Hardy-Weinberg equilibrium (HWE) and average frequency and size of the identified regions. The discordance rates as well as the rates of departure from HWE decrease when we select CNVs with higher confidence scores. We also performed comparisons with two previously published methods, STAC and GISTIC, and showed that the methods we consider are better at identifying low-frequency but high-confidence CNV regions.


The proposed methods for identifying common CNV regions in multiple individuals perform well compared to existing methods. The identified common regions can be used for downstream analyses such as group comparisons in association studies.