Let’s Talk In Situ Sequencing

May 15, 2024

We deep dive into G4X and spatial sequencing for this recap the ABRF 2024 Breakfast Showcase presented by Sabrina Shore, Associate Director of Sequencing Applications, and Rahul Lodhavia, Product Manager.

Imagine if you could sequence RNA, proteins, and variable genomic regions directly in cells and tissues in-situ and at an unprecedented scale and speed. This capability is now a reality with the innovative G4X™ Spatial Sequencer. Building upon the high-speed, high-resolution sequencing chemistry and advanced imaging systems of the G4™ Sequencing Platform, researchers can now discover deeper biological insights faster than ever before with the high-throughput spatial multiomic analysis of the G4X.

Both solutions are rapidly advancing and are poised to transform a wide range of fields, from immunology and oncology to genetic screening and drug discovery, by providing scientists with the ability to interrogate complex biological systems at a level of detail and throughput previously unattainable.

Fast, Flexible Next-Generation Sequencing with the G4

G4 is an exceptionally fast, powerful, and versatile benchtop DNA sequencer. It can produce industry-leading output in under 24 hours, enabling daily sequencing workflows while delivering high-quality results of >85% of bases over Q30. G4 offers unparalleled run flexibility with its 16 individually addressable lanes across 4 flow cells and the ability to run 1-to-4 independent flow cells in parallel. This customizable configuration allows researchers to optimize for speed, throughput, or cost-efficiency based on their experimental needs.

Beyond its incredible versatility, G4 is extremely user-friendly and addresses several pain points experienced with other commercial benchtop sequencers. In addition to G4s intuitive user interface, preparing libraries for G4 sequencing is quick and easy. Singular offers a comprehensive suite of library prep products to enable both de novo and adaptation-based library prep methods. These adaptation methods have been shown to have minimal impact on original library complexity and GC content. Additionally, G4 is highly tolerant to a wide range of library loading concentrations, reducing the need to expend time and costly reagents to repeat experiments over again due to over- or under-clustering. G4 also performs exceptionally well with low-diversity libraries, eliminating the need for PhiX spike-in and giving users more usable reads in each run. These capabilities further G4s utility as a highly effective benchtop sequencer.

Breakthrough Spatial Sequencing with G4X

The G4X is ushering in a new era of spatial multiomic analysis at unprecedented scale. This innovative system performs integrated, multiomic in situ sequencing of RNA transcripts and proteins, along with a fluorescent H&E for every sample. In addition, it boasts the capability of Direct-SeqTM, an innovative methodology to directly sequence variable genomic regions within cells and tissues, unlocking even more powerful multiomic insights. Powered by a barcode-free chemistry utilizing padlock probes and oligo-tagged antibodies, the G4X eliminates the need for cumbersome barcoding strategies.

What truly sets the G4X apart is its remarkable ability to interrogate over 10 times larger sample areas and at single-run throughputs of 20-fold higher than current spatial genomics platforms. Moreover, it provides an additional layer of histological context by correlating the multiomic in-situ sequencing data with co-registered fluorescent H&E imaging on the same tissue section. The transformative capabilities of the G4X have already been demonstrated across a range of sample types, including kidney, tonsil, and even challenging bone marrow specimens.

Advancing Translational Research

Singular Genomics is translating their pioneering spatial sequencing technologies into high-impact biomedical research applications. Collaborative technology access programs are already generating unique insights into treatment response in Acute Myeloid Leukemia (AML) by profiling patient bone marrow samples, and enabling direct sequencing of variable regions, such as the T cell receptor CDR3 region and the immunoglobulin heavy chains on B cells in their native context within tissues.

Looking ahead, Singular is poised to launch an expansive 300-gene, 15-protein immuno-oncology panel optimized for FFPE samples. To rapidly disseminate these capabilities, the company is offering both an early adopter package and research services for running samples or creating custom panels.

A New Frontier in Multiomic Analysis

The powerful next-generation sequencing and high-throughput spatial multiomics capabilities of the G4X can be leveraged to accelerate translational studies across disease areas like immuno-oncology, driving biomarker discovery and the development of precision medicine strategies. Always innovating, Singular Genomics stands at the forefront of this exciting new frontier in multiomic analysis.

Ready to learn more about in-situ multiomics on the G4X?

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Drew Spaventa

Drew founded Singular Genomics in 2016 serving as the CEO and Chairman. Drew is a serial entrepreneur and venture investor in the biotech industry and has been involved in the founding of several successful companies. Prior to Singular Genomics, Drew founded Truvian Sciences, a low volume blood testing technology aimed at making routine blood tests easier, less invasive, and more affordable. Drew was also involved in the founding of Aspen Neurosciences where he co-led the seed financing and helped assemble a world-class team to combat Parkinson’s Disease using a patient’s own stem cells. Drew was also a seed investor and held an operating role in Edico Genome which sold to Illumina in 2018.

Drew received an MBA from the Rady School of Management at the University of California, San Diego and a BA in Political Science and International Relations from the University of California, San Diego.

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