Feb 27, 2018

AGBT gave me the CBGBs!

Scott 10x

AGBT 2018 delivered some great science, talks, posters and time to catch up with old friends. Since our workshop was jam-packed with great information this year, we wanted to share some highlights.

On Tuesday afternoon, it was time for our workshop, "Biology at True Resolution: What Have You Been Missing?" Founder and CSO, Ben Hindson, got the workshop underway with a brief history of 10x Genomics, highlighting how, in a relatively short space of time, we have launched Linked-Reads (2015), Single Cell Gene Expression (2016) and High Definition Immunology (2017). But the message was crystal clear - there is a lot more to come!  The company is currently 250+ people and growing (check out our careers page) and we have deep expertise across diverse disciplines, which has enabled us to invent technologies that cover a huge breadth of research areas from genetic health & cancer, stem cell and developmental biology through to immunology & agrigenomics. Ben closed by reviewing a number of other recent announcements:

  • New Partnership Program which encompasses 10x-Compatible Products and the 10x Certified Service Provider Program.
  • Collaboration with PerkinElmer demonstrating how Linked-Reads are compatible with dried blood spots, giving access to additional biological samples. Read more here.
  • Release of Supernova 2.0 software with increased support for de novo assembly of non-human genomes.
  • Adoption Project.

But, we are just getting started - there is a long way to go!

Professor Aude Chapuis, University of Washington & Fred Hutch CRC, then took the stage to present "Single Cell RNA-seq Unveils Mechanisms of Resistance to T-Cell Therapy". After a refresher on cytotoxic T cells Aude explained how her group is attempting to exploit T-cell biology by using endogenous T cell therapy (CD8+ cells targeting tumour antigens) in Merkel cell carcinoma (MCC), a type of cancer driven by the Merkel cell polyoma virus, a "perfect target for T cell therapy".

Dr. Chapuis showed two examples of patients who relapsed after initial positive response to T cell therapy;  blood and tumour samples were subsequently analysed using the Chromium Single Cell Gene Expression Solution and visualised via t-SNE plots. Single cell gene expression data identified specific clusters of T cells present during initial treatment and positive response, and then showed the absence of those specific T cell populations during relapse.

Next, Dr. Chapuis addressed the question of which T cell receptors (TCRs) should be used for gene therapy. Traditional methods to study this are labor intensive and time consuming and rely on bulk sequencing that masks the identification of biologically and clinically meaningful information. To address this issue, Aude and her team used the Chromium Single Cell Immune Profiling Solution to enable the profiling of thousands of T cells and sequence the full-length, paired alpha/beta chains of TCRs . The results indicated TCRs from T cells isolated from healthy donors have similar function to adoptively transferred "winning" T-cells, suggesting the "healthy" phenotype is restored by a subpopulation of T-cells.

Closing out the workshop with the much buzzed about "What's Next from 10x Genomics?" was Michael Schnall-Levin, VP of Product, R&D and Strategy. Mike announced 3 exciting new single cell products, widening the breath of applications on the Chromium Instrument.

  1. Single Cell Feature Barcoding – This solution will support the simultaneous measurement of gene expression and epitope/protein quantification as well as single cell RNA-seq readouts from pooled CRISPR screens. Reagents & protocols will support custom antibody-oligo conjugation, and compatible products for pre-conjugated antibodies. Consistent with all other solutions from 10x Genomics, analysis will include push-button pipelines for integration of data types, and interactive visualization in a consolidated Loupe Cell Browser.

    And, building on our Immunology applications we are also introducing a new Feature Barcode application: mapping of TCRs to antigens. To illustrate the approach Mike showed example data of peripheral T cells spiked with EBV-specific T cells -the mixed population was labelled with a barcoded MHC-EBV peptide complex and run on the Chromium Single Cell Immune Profiling Solution to yield full-length alpha & beta chains from single T cells . In addition to obtaining full-length alpha and beta chains from single T cells, the number of MHC-EBV peptide complexes bound to each cell was quantified, and then the data combined to link full-length TCR sequences to their antigen target with high specificity and sensitivity.

  2. Single Cell ATAC-Seq – Enables interrogation of chromatin accessibility at single cell resolution to define cell types/states and investigate regulatory mechanisms. This single cell epigenomics approach was used to profile a control sample of 1000 PBMCs; the resulting data were projected in t-SNE plots and cells clusters in patterns that would be predicted for the various cell types and transcriptional states in the sample population.

  3. Single Cell CNV Solution - Enabled by CBGBs (Cell Beads Gel Beads), this solution reveals tumour heterogeneity and clonal evolution and enables study of cancer pathogenesis and progression. The solution includes a turnkey analysis & visualisation pipeline that calls single cell CNV events down to a few 100 Kb. Mike also showed example data to demonstrate that the application meets or exceeds the performance seen in any plate-based method, and has the ability to detect rare clones down to 1%.

The Single Cell CNV Solution was also covered by 10xers Kamila Belhocine and Vijay Kumar as a poster where is received a considerable amount of attention both before and after the workshop!

Additional perspectives and information about these presentations and announcements: