2013-hiseq和proton平台比较-The new sequencer on the block comparison of Life Technology’s.pdf

ORIGINAL INVESTIGATION The new sequencer on the block: comparison of Life Technology’s Proton sequencer to an Illumina HiSeq for whole-exome sequencing Joseph F. Boland ? Charles C. Chung ? David Roberson ? Jason Mitchell ? Xijun Zhang ? Kate M. Im ? Ji He ? Stephen J. Chanock ? Meredith Yeager ? Michael Dean Received: 22 May 2013 / Accepted: 26 May 2013  Springer-Verlag Berlin Heidelberg (outside the USA) 2013 Abstract We assessed the performance of the new Life Technologies Proton sequencer by comparing whole- exome sequence data in a Centre d’Etude du Polymor- phisme Humain trio (family 1463) to the Illumina HiSeq instrument. To simulate a typical user’s results, we utilized the standard capture, alignment and variant calling meth- ods specific to each platform. We restricted data analysis to include the capture region common to both methods. The Proton produced high quality data at a comparable average depth and read length, and the Ion Reporter variant caller identified 96 % of single nucleotide polymorphisms (SNPs) detected by the HiSeq and GATK pipeline. How- ever, only 40 % of small insertion and deletion variants (indels) were identified by both methods. Usage of the trio structure and segregation of platform-specific alleles sup- ported this result. Further comparison of the trio data with Complete Genomics sequence data and Illumina SNP microarray genotypes documented high concordance and accurate SNP genotyping of both Proton and Illumina platforms. However, our study underscored the problem of accurate detection of indels for both the Proton and HiSeq platforms. Background Genome sequence analysis has emerged as a powerful tool to detect a wide spectrum of genetic variation, from single base pair changes (single nucleotide variants), insertion/ deletions, structural rearrangements, chimeric transcripts and gene rearrangements (Gonzaga-Jauregui et al. 2012; Meyerson et al. 2010; Gilissen et al. 2012; Bras et al. 2012; St Hilaire et al. 2011; Veltman and