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Updated: May 26, 2026
16:37
Technical Demonstration of Whole Genome Array Comparative Genomic Hybridization
Published on: August 5, 2008
Performance comparison of whole-genome sequencing platforms
Hugo Y K Lam1, Michael J Clark, Rui Chen
1Department of Genetics, Stanford University, Stanford, California, USA.
Nature Biotechnology
|December 20, 2011
Summary
Whole-genome sequencing platforms from Illumina and Complete Genomics show high concordance for single-nucleotide variants (SNVs) but significant differences for insertions and deletions (indels). Many platform-specific variants are genuine, impacting genome accuracy assessments.
Area of Science:
- Genomics
- Bioinformatics
- Molecular Biology
Background:
- Whole-genome sequencing (WGS) is increasingly utilized, yet comparative accuracy assessments of major platforms are limited.
- Understanding variant calling accuracy and completeness is crucial for reliable genomic data interpretation.
Purpose of the Study:
- To compare the performance of Illumina and Complete Genomics WGS platforms.
- To evaluate the accuracy and completeness of single-nucleotide variant (SNV) and insertion/deletion (indel) calling.
- To assess the biological significance of platform-specific variant calls.
Main Methods:
- High-coverage (∼76×) whole-genome sequencing of an individual using both Illumina and Complete Genomics platforms.
- Comparative analysis of SNV and indel calls between the two platforms.
- Validation of variant calls using target enrichment and genotyping arrays.
Main Results:
- High concordance (88.1%) for SNVs, but low concordance (26.5%) for indels between platforms.
- Tens of thousands of platform-specific SNVs and indels were identified, with validation suggesting >60% are true genomic variants.
- Target enrichment validated 92.7% of concordant SNVs; genotyping arrays showed 99.3% sensitivity.
Conclusions:
- Significant differences exist in indel calling between major WGS platforms, impacting genome completeness assessments.
- A substantial proportion of platform-specific variants are biologically real, necessitating careful consideration in comparative genomics.
- The findings highlight the importance of understanding platform-specific performance for accurate whole-genome sequencing data interpretation.
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