From Individual Cells to Pangenomes: Key Insights from AGBT 2023

Introduction

Earlier this month, seqWell made our annual sojourn to Florida for the Advances in Genome Biology and Technology (AGBT) General Meeting. We spent four exciting days in the company of more than 1,000 genomics scientists and innovators. We spent our time networking and gathering insights on the future of our field.

Below we’ve highlighted some of the innovations and breakthrough research noted at this year’s meeting. We believe these trends could shift how we tackle ongoing challenges in multiomics, sequencing technology, cost, accessibility, and more.

The Trend Toward Multiomics

We’ve long known that examining two or more -omics datasets can offer a closer look into areas like disease mechanisms and gene expression.¹ Now a standard approach to complex questions, the breadth of multiomics applications continues to accelerate, thanks in large part to more powerful tools and sequencing efficiency.

At AGBT 2023, spatial transcriptomics garnered much attention for its promise in disease research. Companies like 10x, Nanostring, and Akoya are integrating co-localized protein detection with visualization of gene expression patterns to maximize deep insights from precious tissue samples.

Researchers are also continuing to map the pangenome—the entire set of genes within a species, consisting of a core genome. In humans, pangenomics aims to expand the reference genome to better represent global human variation. Crop geneticists also build pangenomes of rapidly evolving pathogens to better identify “core” genes that mutate less quickly and could be targeted for disease control.^2,3

As sequencing improves and becomes more cost-effective, more pangenomes will be built faster. These innovations help to deliver on the promise of safeguarding genomics for human and ecological health.

New High-Throughput Sequencing Technology

Not surprisingly, eyes were on both established and emerging sequencing players to announce their latest products and data. As expected, AGBT 2023 attendees saw Illumina’s competition grow on the heels of its new NovaSeq X system.

PacBio announced reduced pricing, enhanced performance, and optimized data for both their Onso and Revio short- and long-read systems. Ultima Genomics presented initial results from its UG-100 instrument, which uses an open flow cell based on a silicon wafer and may deliver the first $100 genome.

Element Biosciences continues to expand chemistry offerings for its AVITI short-read benchtop sequencing system. Their new Cloudbreak chemistry is slated to deliver improved run times and enable a 2 x 300 configuration for more applications while matching the $200 genome. seqWell recently partnered with Element to create an accessible and robust alternative to microarrays for genotyping.^4,5

On the long-read side, Illumina offered more details about its much-anticipated Illumina Complete Long Read (CLR) technology, slated to launch later this quarter. The jury is still out on whether users, especially those currently on Illumina platforms, will opt for CLR or pivot to PacBio’s Revio system, which uses the HiFi workflow and can deliver a 15-18kb read length at about $1000 per genome.

Reductions in Cost

One of the most thrilling outcomes of all this healthy competition is the plummeting cost of the genome.⁶ Illumina reports that its new NovaSeq X can produce 20,000 whole genomes a year at $200 each, but its competitors are dreaming even bigger.

Ultima believes the UG-100 will slash the cost of the genome to $100. That price point is also the touchstone of Complete Genomics’ DNBSEQ-TSOx2 system, one of two new sequencers the company is launching this year—and the largest commercial sequencer to date. As a subsidiary of BGI, Complete Genomics’ viability in the U.S. market depends on the impact of last year’s investment ban.

In any case, we will certainly see the cost of NGS continue to decrease and drive more research and clinical breakthroughs.

Increasing Equity and Accessibility

Falling sequencing costs also factor into broader efforts to break down barriers to genetic testing for all people.

Solenne Correard (University of British Columbia) used her AGBT 2023 presentation to highlight the Silent Genomes Project, an initiative at BC Children’s Hospital Research Institute to bring genomic testing and healthcare to Canada’s Indigenous communities. A major component of this project is developing an Indigenous Background Variant Library of DNA samples from Indigenous individuals and working closely with Indigenous communities to understand how best to apply the data.

Alicia Martin (Broad Institute, Mass General, and Harvard Medical School) also addressed genomic disparities, with particular emphasis on revealing potential biases of polygenic risk scores applications in non-European populations.

Leveraging Innovations

Other individual AGBT presenters showcased how novel NGS technology and applications drive critical work. Here are just a few highlights:

Karen Miga (University of California, Santa Cruz) presented results from her initiative to produce a complete telomere-to-telomere genome assembly with PacBio’s HiFi high-coverage long accurate reads and ONT’s duplex reads. Her work also acknowledges implications on health care, genome diversity, and cell biology.
Heonseok Kim (Stanford University) reviewed a method to detect gene expression and variants from within individual cells using a multiplex CRISPR editor combined with ONT long-read sequencing.^7,8
Beth Shapiro (UCSC) gave a talk on the genetic history of bison—and how ranchers interbred them with cows to produce “beefalo.”⁹ Shapiro’s presentation aligns with seqWell’s recent collaboration with the U.S. Department of Agriculture where researchers evaluated the use of our plexWell Low-Pass 384 library preparation kit for low-coverage WGS of a cattle breeding population.¹⁰

Powering Breakthroughs

We had the honor of sponsoring an afternoon poster session at AGBT 2023. During the conference, we also showcased a 90-minute library prep workflow and presented some of our exciting work through a series of presentations, including:

A novel library preparation technology that links short reads across long DNA fragments and multiplexes samples for fast and affordable parallel phasing of dozens of gene-length amplicons
Custom transposase-based reagents to characterize and quantify transgene-induced editing in the human genome (You can also watch a free webinar about this project.)¹¹

Conclusion

By featuring the full scope of our industry’s trajectory, AGBT drives companies like those in this article to prioritize products that our field needs the most—And seqWell is aware of and a part of this trajectory. We help innovators and researchers rise to the occasion with optimized library prep products, designed to simplify workflows and enable true multiplexing.

We hope to see you back at AGBT next year!

From Individual Cells to Pangenomes: Key Insights from AGBT 2023

seqWell News

Introduction

The Trend Toward Multiomics

New High-Throughput Sequencing Technology

Reductions in Cost

Increasing Equity and Accessibility

Leveraging Innovations

Powering Breakthroughs

Conclusion

References

seqWell Blog

Short-Read Sequencing vs. Long-Read Sequencing: Which Technology is Right for Your Research?

Why does chronic inflammation lead to cancer?

seqWell is designated as a PacBio Compatible Partner with novel tagmentation-based workflow that improves throughput and scalability of long read assays