The Sequencing Bead Array (SBA), a next-generation digital suspension array

• Published in: PloS one 2013-10, Vol.8 (10), p.e76696-e76696
• Main Authors: Akhras, Michael S, Pettersson, Erik, Diamond, Lisa, Unemo, Magnus, Okamoto, Jennifer, Davis, Ronald W, Pourmand, Nader
• Format: Article
• Language: English
• Subjects: Arrays; Bioindicators; Biomarkers; Cervical cancer; Cervix; Chromosomes; Coinfection - diagnosis; Coinfection - virology; Deoxyribonucleic acid; Development and progression; Diagnostic software; Diagnostic systems; Disease Progression; DNA; DNA, Viral - chemistry; DNA, Viral - genetics; Female; Gene Frequency; Gene sequencing; Genomes; Genomics; Genotype; Genotypes; Genotyping; High-Throughput Nucleotide Sequencing - instrumentation; High-Throughput Nucleotide Sequencing - methods; Host-Pathogen Interactions; Human papillomavirus; Humans; Hybridization; Immunoassays; Laboratories; Molecular chains; Oligonucleotide Array Sequence Analysis - methods; Papillomaviridae - classification; Papillomaviridae - genetics; Papillomaviridae - physiology; Papillomavirus infections; Papillomavirus Infections - diagnosis; Papillomavirus Infections - virology; Polymorphism, Single Nucleotide; Reproducibility of Results; Sensitivity and Specificity; Sequence Analysis, DNA - instrumentation; Sequence Analysis, DNA - methods; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Software; Technology; Technology application; Uterine Cervical Neoplasms - diagnosis; Uterine Cervical Neoplasms - virology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0076696

Here we describe the novel Sequencing Bead Array (SBA), a complete assay for molecular diagnostics and typing applications. SBA is a digital suspension array using Next-Generation Sequencing (NGS), to replace conventional optical readout platforms. The technology allows for reducing the number of instruments required in a laboratory setting, where the same NGS instrument could be employed from whole-genome and targeted sequencing to SBA broad-range biomarker detection and genotyping. As proof-of-concept, a model assay was designed that could distinguish ten Human Papillomavirus (HPV) genotypes associated with cervical cancer progression. SBA was used to genotype 20 cervical tumor samples and, when compared with amplicon pyrosequencing, was able to detect two additional co-infections due to increased sensitivity. We also introduce in-house software Sphix, enabling easy accessibility and interpretation of results. The technology offers a multi-parallel, rapid, robust, and scalable system that is readily adaptable for a multitude of microarray diagnostic and typing applications, e.g. genetic signatures, single nucleotide polymorphisms (SNPs), structural variations, and immunoassays. SBA has the potential to dramatically change the way we perform probe-based applications, and allow for a smooth transition towards the technology offered by genomic sequencing.