Thank you to all those who accepted the Single Cell Genomes Scientific Challenge and shared your ideas and inspiration with us! We received high-quality proposals from all over the world, each describing innovative experimental plans to advance research using high-resolution single cell genome sequencing.
Now, we’re thrilled to announce our winners—please join us in congratulating Samira Asgari and Subhajyoti De! Both scientists are making exciting strides in cancer research. Dr. Asgari hopes to identify driver copy number variants (CNVs) in adult T-cell leukemia, while Dr. De is studying the dynamics of cancer progression.
Here at 10x Genomics, we’re honored to jump-start the work of these researchers by awarding each a single cell DNA project. The prizes include a 4-reaction Chromium Single CNV Solution kit, with library prep, sequencing, and bioinformatics support from GENEWIZ. Our Chromium Single Cell CNV Solution profiles copy number variation at the chromosomal or subchromosomal level in hundreds to thousands of cells from the same sample. At a single cell level, you can detect megabase-size events and resolve down to 100s of kilobases with clusters of cells.
For her single cell DNA project, Samira Asgari, a postdoctoral research fellow in Soumya Raychaudhuri’s laboratory at Brigham and Women's Hospital in Boston, Massachusetts, proposed a project focused on adult T-cell leukemia (ATL), a CD4+ T-cell malignancy with an extremely poor prognosis. CNVs contribute largely to ATL’s clonal heterogeneity and are associated with more aggressive disease.
As Dr. Asgari explained, "In a tumour tissue, different genetic mutations give rise to different populations of cells or subclones. Among these, the subclones harboring mutations that resist cell death and promote cell growth generate the most invasive cancerous cells and are the main source of unsatisfactory treatment outcome and resistance to chemotherapy in ATL." The Single Cell CNV solution will help her detect the specific subclones that are driving aggressive disease and match each individual cell to its associated genetic copy number changes.
Since bulk methods can only recover the average genetic profile of the tumor, they may miss variants in subclones related to drug resistance. Dr. Asgari plans to study CD4+ T cells from ATL patients, recruited by Juan Carlos Ramos at the University of Miami Health System, to reconstruct the genetic phylogeny of aggressive subclones and identify CNVs that happen early during clonal evolution. The results of this study could lead to the identification of clinically relevant CD4+ T-cell subclones to serve as drug targets for ATL, and/or the discovery of novel driver genes that can be used as markers for early disease detection.
Subhajyoti De, an assistant professor at Rutgers Cancer Institute of New Jersey, aims to use single cell DNA sequencing to understand the timing of tumor cell spreading and metastatic growth in pancreatic cancer patients. His team has isolated metastasized pancreatic tumor cells and used the Chromium Single Cell Gene Expression Solution to identify multiple tumor cell populations with distinct gene expression profiles. Now, Dr. De and his team will use the Chromium Single Cell CNV Solution and a novel bioinformatics framework to investigate the genetic basis of heterogeneity in pancreatic cancer.
"The Single Cell CNV Solution is particularly ideal to address our research question—whether metastasis occurs early during pancreatic cancer progression, a question otherwise difficult to study using alternative techniques," explained Dr. De.
Using the CNV solution, the team will be able to directly identify genomic copy number alterations at single cell resolution, allowing them to determine the phylogenetic relationship between subclonal cell populations within the primary tumor and in those in metastatic lesions. Dr. De anticipates that his proposed research will provide novel insights into the metastasis of pancreatic cancer by potentially challenging the paradigm that metastasis is a late event in cancer progression.
Dr. Asgari and Dr. De will begin their proposed experiments soon, and we look forward to seeing the exciting results in the next several months!
Resources and Additional Reading
AGBT Fellowship in Cancer Genomics—Another exciting opportunity for research support!
Advances in Genome Biology and Technology (AGBT) is partnering with the Damon Runyon Cancer Research Foundation to award a new fellowship in honor of Elaine R. Mardis, a founding member of the AGBT Scientific Organizing Committee and world renowned genomics pioneer. Applications for the AGBT Elaine R. Mardis Fellowship in Cancer Genomics are due August 15th.