Journal Article

Performance comparison of exome DNA sequencing technologies

Chen, Rong, Butte, Atul J, Euskirchen, Ghia, Clark, Michael J, Lam, Hugo Y K, Snyder, Michael, Karczewski, Konrad J, Chen, Rui

2011

Overview

Capturing and sequencing only the coding regions of the human genome leverages resources in the pursuit of rare disease-causing mutations. Clark et al . compare the performance of three leading exome-capture methods and their advantages over whole-genome sequencing. Whole exome sequencing by high-throughput sequencing of target-enriched genomic DNA (exome-seq) has become common in basic and translational research as a means of interrogating the interpretable part of the human genome at relatively low cost. We present a comparison of three major commercial exome sequencing platforms from Agilent, Illumina and Nimblegen applied to the same human blood sample. Our results suggest that the Nimblegen platform, which is the only one to use high-density overlapping baits, covers fewer genomic regions than the other platforms but requires the least amount of sequencing to sensitively detect small variants. Agilent and Illumina are able to detect a greater total number of variants with additional sequencing. Illumina captures untranslated regions, which are not targeted by the Nimblegen and Agilent platforms. We also compare exome sequencing and whole genome sequencing (WGS) of the same sample, demonstrating that exome sequencing can detect additional small variants missed by WGS.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/61/212/748 / 631/61/514/1948 / Agriculture / analysis / Baits / Base Composition - genetics / Base Sequence / Bioinformatics / Biological and medical sciences / Biomedical and Life Sciences / Biomedical Engineering/Biotechnology / Biomedicine / Biotechnology / Blood / Deoxyribonucleic acid / Diverse techniques / DNA / DNA sequencing / Exome - genetics / Exome sequencing / Fundamental and applied biological sciences. Psychology / Gene targeting / Genetic engineering / Genetic technics / Genetic variation / Genome, Human - genetics / Genomes / Genomics / Humans / Identification and classification / Life Sciences / Methods / Methods. Procedures. Technologies / Molecular and cellular biology / Nucleotide sequencing / Open Reading Frames - genetics / Polymorphism, Single Nucleotide - genetics / Properties / RNA, Messenger - genetics / Sequence Analysis, DNA - methods / Sequence Analysis, DNA - standards / Sequence Deletion - genetics / Synthetic digonucleotides and genes. Sequencing