Comprehensive assessment of array-based platforms and calling algorithms for detection of copy number variants.

Pinto D, Darvishi K, Shi X, Rajan D, Rigler D, Fitzgerald T, Lionel AC, Thiruvahindrapuram B, Macdonald JR, Mills R, Prasad A, Noonan K, Gribble S, Prigmore E, Donahoe PK, Smith RS, Park JH, Hurles ME, Carter NP, Lee C, Scherer SW, Feuk L

Nat. Biotechnol. 29 (6) 512-520 [2011-05-08; online 2011-05-08]

We have systematically compared copy number variant (CNV) detection on eleven microarrays to evaluate data quality and CNV calling, reproducibility, concordance across array platforms and laboratory sites, breakpoint accuracy and analysis tool variability. Different analytic tools applied to the same raw data typically yield CNV calls with <50% concordance. Moreover, reproducibility in replicate experiments is <70% for most platforms. Nevertheless, these findings should not preclude detection of large CNVs for clinical diagnostic purposes because large CNVs with poor reproducibility are found primarily in complex genomic regions and would typically be removed by standard clinical data curation. The striking differences between CNV calls from different platforms and analytic tools highlight the importance of careful assessment of experimental design in discovery and association studies and of strict data curation and filtering in diagnostics. The CNV resource presented here allows independent data evaluation and provides a means to benchmark new algorithms.

Affiliated researcher

PubMed 21552272

DOI 10.1038/nbt.1852

Crossref 10.1038/nbt.1852

pii: nbt.1852
pmc: PMC3270583
mid: NIHMS346122
GEO: GSE25893

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