American Society of Human Genetics (ASHG)

Mitu Chaudhary is a Sr. Director, International Business Leader, Sequencing Systems at Roche Sequencing Solutions since Feb 2023. She is responsible for the full product lifecycle of sequencing systems that includes AXELIOS NGS and automation platforms. She has about 20 years of professional experience, holding business leader and product management positions at 10x Genomics, Illumina and Agilent Technologies prior to Roche. Mitu holds a Master's Diploma in Business Administration (MBA) with a specialization in International Marketing and a Bachelor of Technology, Engineering.

Jagadeeswaran Chandrasekar is the Director of Advanced SBX Applications at Roche Sequencing Solutions. He earned his PhD in Chemistry from the University of Illinois at Urbana-Champaign in 2016. Following his doctoral studies, Jagdeesh began his career as a chemist and biochemist at Stratos Genomics, where he contributed to advancing SBX technology, an innovative approach to genome sequencing. In his current role, he continues to specialize in SBX technology, with a strong focus on library preparation and the development of advanced workflows.

SBX uses a biochemical process to encode the sequence of a target nucleic acid molecule into a highly measurable surrogate polymer called an Xpandomer. Xpandomers encode the sequence information into high signal-to-noise reporters, enabling high-fidelity, single-molecule nanopore sequencing using a highly parallel CMOS-based sensor array. We will provide more information on the capabilities of the AXELIOS system and how it leverages SBX technology to drive very high speed, throughput and flexibility. We will also dive into more details of SBX-duplex (SBX-D) which links both strands of the target DNA in a single sequencing read. This approach uses intramolecular consensus of the complementary reads to identify discordant calls and achieve high accuracy. We will present how SBX-D can be used for very high performance for whole genome sequencing (WGS) for genomic DNA, including from low quality FFPE as well as cfDNA in the context of minimal residual disease (MRD) research. With throughput rates in excess of 500 million bases per second, this advancement in molecular measurement allows for flexible system operation across a range of throughput scales and read lengths, enabling users to better optimize workflows and rethink how sequencing applications can be implemented. 

Disclaimer: The Sequencing By Expansion (SBX) technology is in development and not commercially available. The content of this material reflects current study results and/or design goals.The Sequencing Platform based on SBX Technology will be launched for Research Use Only. Not for use in diagnostic procedures.

With nearly 30 years of experience working on the cutting edge of biotechnology, Mark’s passion is to conceive and develop innovative and transformative technologies. His vision of creating a next generation DNA sequencing technology that would enable broader use in healthcare led him to co-invent the SBX technology in 2007. The same year, he co-founded Stratos Genomics, where he held roles as president and Chief Science Officer then later as CEO. In 2020, he led Stratos through the company’s acquisition by Roche, where the SBX chemistry could be brought together with Genia’s massively parallel IC technology. Mark, who heads all SBX research at Roche, is an inventor on over 20 issued US patents.

Katie helps drive product innovation and shapes strategic direction to advance BCL’s mission. She has been at the Broad Institute since 2009, with experience spanning lab operations, clinical sequencing, and next-generation sequencing technologies.

The technology enables high-fidelity, single-molecule nanopore sequencing using a highly parallel CMOS-based sensor array. It also enables a flexible system operation across a range of throughput scales and read lengths, enabling users to better optimize workflows and rethink how sequencing applications can be implemented.

Mark Kokoris, inventor of SBX Technology,  will cover improvements to existing workflows and introduce novel research applications, expanding SBX's capabilities into multiomics. This includes an approach to leverage a longer read workflow to read the cDNA fragment from both the 3’ and 5’ ends. This allows for studies that were not possible on traditional short read platforms such as isoform detection and potentially enhanced differential transcript usage for infection. We will also demonstrate how the SBX-Duplex methodology is combined with high-fidelity methylation mapping. This results in a high efficiency intra-molecular consensus workflow which can have significant advantages in research applications, including liquid biopsy-based cancer detection and identification of novel epigenetic biomarkers. 

The session concludes with a presentation from the Broad Clinical Labs on a WGS workflow in development that, when tested on 10 research samples, allowed for relatively rapid turnaround times. Current robust methods achieve WGS from sample to VCF in 2-3 days, while achieving same-day WGS has historically faced challenges in robustness. This research workflow with streamlined lab and data analysis processes, leveraging the SBX technology, enabled end-to-end completion within a day by a single technician under test conditions. The Broad Clinical Labs tested this workflow on 10 consented research samples obtained in collaboration with Boston Children’s Hospital (BCH). Turnaround times were under 6 hours from DNA to VCF for all runs. This illustrates the potential for ultra-rapid WGS to deliver robust yet rapid results.

Brian is a bioinformatics software developer and data analyst with a focus on leveraging transcriptomics for studies in genomics and biomedical applications. Brian has a passion for biological software development and scientific research, with over 20 years of experience at world renowned genome research institutes including the The Institute for Genomic Research (TIGR) and J. Craig Venter Research Institute.

Emma's research focuses on integrating functional genomics and clinical data in order to understand how genetics contributes to the patient-to-patient heterogeneity in treatment response. She completed her PhD research under the supervision of Professor Julian Knight at the University of Oxford. Emma conducted her postdoctoral research in Professor Soumya Raychaudhuri’s lab at Brigham and Women’s Hospital, Harvard Medical School and the Broad Institute. 

After he graduated from UTokyo in 1999, Dr. Suzuki spent one year at Genome Science Center, RIKEN and then moved on to UTokyo where he researched full-length cDNA sequencing analysis. He has been a professor at UTokyo since 2013. His specialties include full-length cDNA, transcriptome, transcriptional start site, next-generation sequencing, cancer genomics, and spatial biology.

Brian Haas from the Broad Institute discusses the characterization of cancer transcriptomes and fusion isoforms using SBX. He presents the sequencing and analysis of nearly 100 cancer cell line transcriptomes, demonstrating how SBX's extended read lengths improve the detection of transcript splice isoforms and capture full-length transcripts. His work evaluates isoform detection, splicing diversity, and the resolution of alternative splicing events relevant to cancer, as well as the identification and characterization of fusion transcript isoforms, which are key drivers of oncogenesis. The findings establish SBX's utility for advancing cancer transcriptomics research.

Emma Davenport from the Wellcome Sanger Institute presents research on using long-read bulk RNA-seq to understand variation in response to infection, specifically melioidosis, a bacterial infection with varied clinical outcomes. Her team generated short-read bulk RNA-sequencing and whole genome sequencing for over 1,000 individuals from Thailand and will use longer-read bulk RNA-seq in a subset (n=90) to explore differential transcript usage in response to infection.

Yutaka Suzuki from the University of Tokyo shares results from an initial trial of the Roche SBX sequencer for sequencing-based spatial gene expression analysis using Visium HD. He notes that while powerful, sequence-based approaches require high sequencing depth (1-5 billion reads), making them costly. His analysis of banked  human lung cancer libraries using Visium HD libraries sequenced with SBX yielded 15 billion reads in just one hour. The results showed almost perfect consistency with Illumina reads in spatial distribution of total UMI and representative genes (Pearson's correlation coefficient >0.99), with an average accuracy of 99.7%. Suzuki discusses how SBX could be integrated into core laboratories worldwide alongside hybridization-based approaches.