The new sequencer on the block: comparison of Life Technology's Proton sequencer to an Illumina HiSeq for whole-exome sequencing

Abstract

We assessed the performance of the new Life Technologies Proton sequencer by comparing whole-exome sequence data in a Centre d'Etude du Polymorphisme 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 methods 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. However, 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 supported 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.

Fig. 1

Distribution of sizes of insertion/deletion polymorphisms (indels) by a all indels detected by Proton and Illumina overall, b indels detected in common by both Illumina and Proton, c indels detected by Illumina only and d indels detected by Proton only. Blue bars represent indels previously reported in dbSNP build 137, while red bars represent novel indels

Fig. 2

Venn diagrams of the overlap in numbers of variant calls by sequencing platform for a SNPs and b indels