The annual American Society of Human Genetics (ASHG) conference was held October 16–20 in San Diego, California. Total registration, including exhibitors, staff and press, rose 21.2% from last year, when the conference was held in Orlando, Florida, to 9,043. The number of scientific attendees increased 19.3% to 7,058. The number of exhibitors grew 9.4% to 256. In 2016, the last time the show was held in San Diego, it attracted 7,998 total attendees (see IBO 10/31/18).

Presentations

The presentations that IBO attended illustrated both the advancements and continued challenges in genomics research. The value of the results of population-scale genomic analyses was evident by the number of presentations involving samples collected as part of the UK Biobank. On Wednesday morning, Sara Rashkin, PhD, presented “Pan-cancer Analysis Detects Novel Genetic Risk Variants and Shared Genetic Basis in the UK Biobank Cohort,” discussing her research finding a shared genetic basis of various cancer types based on an analysis of 18 cancer phenotypes. Results from GWAS for each phenotype and cancer outcome revealed 49 regions associated with multiple cancers, and 23 SNPs associated with both positive and negative cancer outcomes.

Introducing the session “Large-Scale Functional Annotation of Variants of Uncertain Significance,” Stan Letovsky, PhD, of LabCorp, highlighted the value of high-throughput functional assays for genomic analysis.  As he stated, “Functional annotations are often the only information available regarding the clinical impact of rare variants.” In the future, such assays may be scaled up to whole-genome studies.

As part of this session, in the presentation “Understanding Tumor Heterogeneity from Single Cell Sequencing of Genomes, Transcriptomes and Epigenomes,” Eham Aziz, PhD, of Memorial Sloan Kettering Cancer Center described her work using single-cell RNAseq to characterize “a full range of phenotypic states occupied by immune cells in the breast tumor microenvironment.” In particular, she discussed her labs’ efforts to create bioinformatics solutions to address the challenges of normalizing scRNAseq data. Ideally, she said, there would be different normalization for each cell type, as normalization independent of cell type, does not adequately account for cellular variation.

Based on a collaboration with 10x Genomics, Monte Winslow, PhD’s presentation “Single-cell phenotypes and cancer genotypes” reviewed his work exploring the diversity of the response of single cells to cancer. Specifically, he listed the diversity of cell growth potential, the impact of the genotype of this potential and intratumor cancer cell heterogeneity, as well as using CRISPR/Cas9 to edit cells in mouse models to study lung cancer tumors. He noted the need for better methods for quantification of tumor sizes, which currently rely on histology and imaging. CRISPR/Cas9 was used to generate greater genomic diversity in the mouse models. Sequencing of integrated barcoded vectors enabled the quantification of cancer cell numbers.

Product Introductions

At the show, 10x Genomics launched an update to its Chromium Single Cell Gene Expression Solution, including a new version (v3) of the Chromium Single Cell 3’ Reagent Kit. With greater sensitivity, the v3 solution can now measure twice the number of genes in the same experiment, or the same the number of genes by sequencing only half the number of samples, according to Giovanna Prout, director of Strategic Marketing, Single Cell Genomics, at 10x Genomics.

10x Genomics also highlighted its Chromium Single Cell ATAC Solution (Assay for Transposase-Accessible Chromatin) for epigenetic research using single cells, building on its acquisition in August of Epinomics (see IBO 8/31/18). Compared to other approaches for examining chromatin accessibility such as ChIP-Seq, ATAC-seq has higher sensitivity, improving detection of accessible regions in rarer cells, and requires smaller sample amounts. The 10x Chromium Single Cell ATAC Solution works with as few as a hundred cells. Deliveries began next week.

The company also showcased its Feature Barcoding technology, available in December, with kits for measuring CRISPR perturbation and protein surface cells, each done in parallel with gene expression measurements. Feature Barcoding capability also enables single-cell immune profiling with cell surface proteins, part of the technology’s ability to measure gene expression, receptor-pair full sequences, cell surface proteins and cell specificity in the same cell. The company is currently working with BioLegend and Immudex as non-exclusive partners, who are both members of the company’s Compatible Partnership Program. The company also plans to partner with additional companies, including guide RNA suppliers for the CRISPR application.

At ASHG 2018, Pacific Biosciences announced a major leap for its SMRT sequencing technology. The company launched v6.0 software and v3.0 reagents for its Sequel long-read sequencing system. The product updates increase read length from up to 30 kb for gDNA and up to 100 kb for amplicons, according to Pacific Biosciences Chief Scientific Officer Jonas Korlach, PhD. The new enhancements are also a major development in that they increase single-molecule read accuracy to over 99%, on par with Illumina’s short-read sequencing and Sanger sequencing, according to Dr. Korlach. The new v6.0 software update also provides faster analysis times, benefitting applications such as targeted sequencing and RNA transcript isoform sequencing. These developments will impact Pacific Biosciences’ applications in the clinical markets. SMRT technology is already being used for clinical research, including research into genes of pharmacogenomic significance and to resolve structural variation.

Pacific Biosciences told IBO that SMRT sequencing will be able to compete directly with Illumina on price per whole genome as the company will next year release the 8M SMRT Cell, with eight times higher throughput. Dr. Korlach said that it will now be more cost effective for researchers to use Pacific Biosciences on all sample types as opposed to just high-value samples. The use of SMRT technology will allow access to structural variation at a price comparative to Illumina’s for whole genomes. Other applications include studying rare diseases to further increase solve rates, and de novo assembly of population-specific reference genomes.

Other NGS product launches at the show included Roche’s AVENIO Tumor Tissue Analysis Kits for research, consisting of the AVENIO Tumor Tissue Targeted Kit, Expanded Kit and Surveillance Kit. The Kits enable a single workflow for measurement of SNVs, indels, fusions and CNVs. This follow last year’s introduction of the AVENIO ctDNA Targeted Kit liquid biopsy, providing a tissue equivalent to that kit. According to the company, it is the only supplier with such panels for both liquid biopsy and tissue analyses, enabling testing for similar results.

Among the products Agilent Technologies promoted at its booth was the Agilent XT HS and XT Low Input  Enzymatic Fragmentation Kit. The Kit enables fragmentation of 10–200 ng of DNA. As Kamni Vijay, Vice President and General Manager, Agilent Genomics Division told IBO, the Kit is another example of Agilent providing its NGS cusomters with a full range of options for their workflows. She also emphasized the company’s ability to offer customized solutions for NGS as a differentiating factor. Other differentiators from NGS competitors include Agilent’s ability to offer its solutions with its own automation and its molecular barcoding IP, acquired with its purchase of Population Genetics Technologies (see IBO 7/31/17).

Mission Bio and NanoCellect were among the companies exhibiting products introduced within the last year. MissionBio’s Trapestri system is a cell capture solution for targeted single-cell analysis using DNA. Up to twenty thousand cells can be analyzed at a time, resulting in a decreased cost compared to lower-capture techniques, such as FACS, according to the company. Applications include QC of CRISPR/Cas9 techniques. Addressing the need for low-cost cell sorting solutions, NanoCellect exhibited the WOLF Cell Sorter. Disposable chips guarantee a sterilized solution with 3-color, 5-parameter sorting at 300 cells per second. The base cost of the system is $85,000. Applications include validity of CRISPR-modified human iPSC cells. At the show, the company also discussed an informal partnership with QIAGEN for single-cell RNAseq using the WOLF Cell Sorter and QIAGEN QIAseq UPX 3’ Transcriptome kit.

Also exhibiting was TriLink BioTechnologies, part of the Maravai LifeSciences group of companies. The 170-person firm offers synthesis of modified nucleic acid products and NGS sample preparation kits, as a direct seller, as well as supplier of kit contents to both research and diagnostic tool companies. Specialties include customized offerings for complex applications, including synthetic RNA and DNA oligonucleotides for bioprocessing, and mRNA with the proprietary enzymatic capping technology, CleanCap. Growing markets for the company’s products include gene editing and mRNA therapeutics.

ASHG 2019 will take place October 15–19 in Houston, Texas.