Roche’s SBX platform reaches unprecedented speeds and unlocks multi-omics integration and research previously out of reach for traditional short read platforms

The recent annual meeting of the American Society of Human Genetics (ASHG) served as the crucial stage for a series of major announcements regarding Roche’s sequencing by expansion (SBX) technology. These advances showcased the platform’s capacity for ultra-rapid whole-genome sequencing (WGS) and its flexibility in resolving complex biological queries, from transcript isoforms to concurrent methylation mapping, to enable research and applications that were previously not feasible.

At the core of SBX technology is a sophisticated and proprietary chemistry that translates DNA into an "Xpandomer" - a surrogate polymer 50 times longer than the original molecule  - for sequence measurement. This chemistry, combined with a high-throughput sensor array, forms a  platform that is fundamentally designed for flexibility and performance, allowing efficient scaling for various future applications based on throughput, read length, and time to result.

Perhaps the most immediately striking news from the conference was the confirmation that the SBX technology had achieved a GUINNESS WORLD RECORDS™ title for the fastest DNA sequencing technique.

The ultra-rapid application, known as SBX-Fast, completed the full workflow—from library preparation through VCF generation—in just 3 hours and 59 minutes, surpassing the previous benchmark of 5 hours and 2 minutes. This breakthrough method provides speed and accuracy with an amplification-free workflow that starts with gDNA from sources like blood, saliva, or tissue. The Broad Clinical Labs and Boston Children’s Hospital subsequently applied this method in a  research study to demonstrate same day whole-genome analysis for multiple samples. 

Addressing the development of this fast method, Mark Kokoris, Head of SBX Technology at Roche Diagnostics Solutions, stated: "Our research teams, in developing SBX-Fast, meticulously optimized every step of the sequencing workflow. This included DNA isolation, library preparation, Xpandomer synthesis, sequencing, and the acceleration of primary analysis, mapping and alignment and variant calling. While the dramatic reduction in the timing led to a Guinness World Record, the true impact lies in what speed and accuracy shown over multiple days and across multiple samples can mean for the scientific community engaged in deciphering complex conditions."

The SBX platform also showed significant progress in RNA sequencing through the SBX Simplex Longer RNA (SBX-SLR) method, which targets longer and bi-directional reads. SBX-SLR delivers exceptional throughput, achieving between 2.5 and 4 billion reads per hour with an average read length of 400–600bp.

Longer reads can be vital for resolving transcript isoforms, a regulatory axis of biology that occurs in over 90% of human genes but can be left under-resolved by short-read assays. In the data presented SBX-SLR enabled greater unambiguous isoform identification. In studies using DepMap cancer cell lines, the platform achieved 95% saturation of identifiable isoforms.

Furthermore, in a project utilizing SBX-SLR to study a Melioidosis sample cohort (comprising healthy, survivors, and non-survivors), researchers were able to examine differential gene expression and identify differentially spliced isoforms including in genes associated with immune function and regulation, such as IL1RL1 and IL18R1.

A major advancement was the introduction of SBX-Duplex Methylation (SBX-DM), which enables the concurrent detection of DNA variants and methylation signals from a single library preparation.

 The research workflow combines SBX-Duplex, a methodology in which both strands of the target DNA are linked in a single read, with a high-fidelity methylation mapping method, TET-assisted pyridine borane sequencing (TAPS), a technology in development by Watchmaker Genomics. This integrated workflow allows for simultaneous DNA variant calling and methylation calling using standard DNA aligner and XOOS methylation caller.

This capability is central to the SBX Multi-Omics framework, which combines SBX-SLD (DNA), SBX-SLR (RNA), and SBX-DM (Methylation). This powerful combination facilitates sophisticated analysis, including long-range phased haplotypes, allele-specific methylation analysis, and phased allele-specific expression.

Moreover, the integration of these signals may have advantages in research applications, for example in Minimal Residual Disease (MRD) detection. When sequencing cell-free DNA (cfDNA), SBX-DM successfully detected methylation signals consistent with tissue methylation. This methylation data provides complementary information to cfDNA SNP detection, potentially improving MRD detection in low-TMB samples.

Reflecting on the platform's comprehensive capability across different research domains, Mark Kokoris also noted: "We designed the sequencing by expansion chemistry for flexibility and performance, allowing us to efficiently scale for a wide range of applications, from ultra-high-throughput duplex sequencing to longer reads that enable unambiguous isoform identification and concurrent DNA and methylation analysis, unlocking true multi-omic discovery."

These advances emphasize Roche’s commitment to advancing the entire NGS value chain, moving beyond individual tools to integrated solutions that accelerate research and translational applications across whole genome, whole transcriptome, multiomics, and epigenetics.