AACR 2018: From NGS to Single-cell Genomics and Beyond

The 109th Annual Meeting of the American Association for Cancer Research (AACR) meeting took place in Chicago, Illinois, from April 14 to April 18. Attendance increased around 3% this year to more than 22,600. The number of exhibitors jumped 11.8% to 556. The meeting’s presentations and exhibits showed clear enthusiasm for progress in personalized medicine and immumno-oncology. The opening plenary session featured updates on immune checkpoint therapies, and another session discussed how advancements in cancer genomics can lead to the identification of new therapeutic biomarkers and more personalized medicine. Among the most exciting lab technology updates were developments in imaging and single-cell resolution products, especially for use in investigating tumor heterogeneity.

 

Agilent Technologies: Science Overview

Bridging a multitude of analysis techniques, Agilent Technologies held a press conference showcasing how customers utilize their products in the fight against cancer. Customer speakers touched on the subjects of genomics, clinical MS in prostate cancer diagnosis, and cell metabolism. Agilent’s technology covers a broad range of the various cancer characterization workflows from changes in nucleic acids, to proteomics, to cell respiration to help customers better understand the development of cancer as well as potential leads for therapies.

 

Thermo Fisher Scientific: NGS Workflows

In conjunction with the conference, Thermo Fisher Scientific announced the launch of the International Childhood Oncology Network (ICON), in which members will share data, best practices and protocols. ICON addresses pediatric, childhood and young adult cancers, whose recurrent somatic variations can be different than adults for the same disease. Thermo Fisher also introduced the NGS-based Oncomine Childhood Cancer Research Assay, developed with the Children’s Hospital of Los Angeles. It targets the unique mutations associated with childhood cancers, and is the first Assay to detect RNA gene fusions and DNA mutations simultaneously. The Assay interrogates 203 genes and 1,700 fusion transcripts. As Thermo Fisher told IBO, childhood cancers have a different molecular signature than adult cancers and thus require a different type of panel. The panel is priced in the same range as other cancer panels.

Additionally, Thermo Fisher launched the Applied Biosystems Arcturus Cellect Laser Capture Microdissection System, a smaller-sized, next generation laser-capture microdissection device. Supporting the cancer research workflow, the System combines a gentle IR laser to capture cells and a UV laser to extract them. The device should be available by mid-year at a price of around $125,000–$175,000.

 

Illumina: TMB Panels

Illumina also exhibited at the show. As Garret Hampton, Executive Vice President of Clinical Genomics at Illumina, told IBO, the company is focused on advancing personalized medicine, both through internal development and partnerships. In particular, Illumina highlighted its focus on test panels for estimating tumor mutational burden (TMB). Developments in this area include the TruSight Tumor 170 Panel, launched last year, which accesses fusions, splice variants, insertions/deletions and SNVs and amplifications all in one assay, using DNA and RNA. The company also recently announced a partnership with Bristol-Myers Squibb to develop its TruSight Oncology 500 assay as a companion diagnostic for oncology therapeutics, and which would include predictive genomic biomarkers such as TMBs.

 

10x Genomics: Single-cell Solutions

10x Genomics announced the launch of its Chromium Single Cell CNV Solution. Offering a scalable, high-throughput method for parallel profiling of single-cell genomes, the Single Cell CNV Solution is the latest addition to the 10x product portfolio that uses the Chromium Controller instruments, a microfluidics platform that is compatible with short-read Illumina sequencers, to characterize the genomic landscapes of thousands of individual cells. The Single Cell CNV Solution uses the Chromium Controller in a two-step process to: one, capture individual cells, cleanse and isolate genomic DNA within a gel bead; and two, barcode single cells and construct DNA libraries via the formation of cell bead–gel bead (CGBG) droplets. The Solution scales from hundreds to thousands of cells. Advantages include the ability to run scDNAseq and scRNAseq in parallel on the same sample. 10x will also offer a software suite that will analyze and visualize the CNV data collected (Cell Ranger DNA Analyses Pipelines and Loupe scDNA Browser).

The Single Cell CNV Solution can be used to promote understanding of tumor heterogeneity, clonal architecture and evolution, neuronal mosaicism, and more. Shipments of the CNV solution is expected to begin in July 2018; however, many early access users presented posters and presentations at AACR. In addition, new genomic solutions to the 10x Chromium System are in development and are slated to be released later this year, featuring chromatin/epigenomic analyses (ATAC-seq) and protein/phenotype analyses (single-cell-feature barcode technology).

Fluidigm: Imaging and Gene Expression

Fluidigm highlighted several systems at AACR including the Hyperion Imaging System for imaging mass cytometry.  The system enables the user to simultaneously visualize 4 to 37 proteins, transcending the current capabilities of fluorescent IHC. The system allows for subcellular resolution while simultaneously preserving tissue structure and cellular morphology. The user friendly viewing capabilities include images that are ready for analysis in minutes and are easily exported for secondary analysis.

For the the Helios CyTof mass cytometry system, Fluidigm recently introduced the Maxpar Human Immune Monitoring Panel Kit for deep profiling of PBMC [Peripheral blood mononuclear cells] in a single tube. The simplified workflow includes the ability to easily stain PBMC with 29 antibodies simultaneously and analyze results with third-party software. This software includes the Gemstone, which enables automated probability state modeling of viable single cells, population identification and quantification, and rapid results reporting with mass cytometry.

For its complete mass cytometry portfolio, the company offers over 600 Maxpar antibodies, pre-designed panels and the flexibility to conjugate new antibodies. The kit is designed for human immune monitoring for early translational studies and multicenter clinical research.

The company also highlighted the Juno system for automated targeted NGS library preparation. Its offerings for the system include D3 Assay Design custom services. In addition, the company is developing an expanding menu of high-value genetic assays for the system.

For use on the Juno, the new Advanta CFTR NGS Library Prep Assay is designed to be more comprehensive for CFTR (cystic fibrosis transmembrane conductance regulator) analysis than traditional genotyping. To reduce the cost per sample and hands-on time of current NGS targeted sequencing library prep workflows, the Assay automates target enrichment of CFTR variants from each of the gene’s 27 exons and selected intronic regions. This product is commercially available.

 

Bio-Rad Laboratories: Digital PCR

On the exhibit floor, Bio-Rad Laboratories previewed its latest Droplet Digital PCR system, the QX ONE. Scheduled to be begin shipping next year, the system leverages 4-color multiplexed digital PCR instead of 2 color. In addition, it is fully automated and up to 16 samples can be processed. Droplet generation, thermal cycling and droplet reading are integrated into one system. The system itself is expected to be priced at around $195,000, with a estimated cost per run of $3–$5 per sample.

 

NanoString Technologies: Gene Expression and Spatial Profiling

NanoString Technologies announced the release of the Breast Cancer 360 (BC360) gene expression panel for its nCounter system. The BC360 panel is the latest addition to NanoString’s portfolio of RUO expression panels. Encompassing 33 biological signatures and 770 target genes including breast cancer subtype classification, key pathway analysis and tumor inflammation, the BC360 panel enables researchers to gain an understanding of the breast cancer microenvironment, tumor heterogeneity, immune response and more. With a simple workflow, low-sample input, and results within 24 hours, the BC360 is designed to allow for fast characterization of breast cancer, with translational implications for treatments and precision medicine. In addition, NanoString is also offering a custom BC360 data analysis service for $500/sample.

Also highlighted at AACR were the latest developments in NanoString’s digital spatial profiling (DSP) technology. The DSP platform combines multiplexed RNA and protein analysis with microscopy to resolve spatial profiling of the tumor microenvironment at single-cell resolutions. Using nCounter digital optical barcoding technology, DSP technology couples RNA probes and/or antibodies with photocleavable oligonucleotide tags that can be quantitated and mapped to a tissue sample. Currently, DSP is only available via NanoString’s technology access program, but is anticipated to be commercially available in early 2019.

 

Greiner Bio-One: 3D Cell Models

Greiner Bio-One exhibited Nano3D Biosciences’ products at the show. Nano3D utilizes magnetic 3D cell culture technology to form 3D cell models in vitro. Aggregation occurs using either levitation or printing. The company’s products include the NanoShuttle-PL reagents, and a number of single-well and microplate assembly kits, as well as accessories. The advantages of the technology, according to Greiner Bio-One, is that it is the only scalable 3D cell culture system with single well to 1,536 wells using the same workflow. In addition, it is the only 3D system utilizing a 2D workflow and does not require specialized equipment, media or artificial substrates. Designed for 3D cell culture, target applications are life science research, drug discovery, toxicology testing, cancer research, stem cell research, tissue engineering and personalized medicine.

 

LifeNet Health: Microtumor Assays

LifeNet Health was also present at the show. Last year, the company added a Life Sciences Division, which specializes in biomedical research, particularly in pharmaceutical discovery and preclinical testing.  The company’s latest product, the 3D Hubiogel, is a predictive fully-human microtumor assay platform. Hubiogel is a growth factor–free, non-denatured extracelluar matrix (ECM) derived from human amnions. This ECM supports the generation of microtumors which translate into 3D tumor assay models.  The product improves preclinical success rates by identifying lead bioactive candidates, providing an advantage in animal studies.  This assay platform is also designed to improve standardization of results by minimizing variance. This method of testing allows for informed decisions to be made before engagement in expensive in vivo studies and prevent failure at later stages of clinical trials.

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