Uncovering the intricate details of individual cell functions on a grand scale

Researchers at the OHSU Knight Cancer Institute have developed a groundbreaking method that significantly improves the efficiency of single-cell sequencing, leading to a third reduction in sequencing costs. This innovation is set to revolutionise the understanding of cancer, brain function, immunity, and other biological processes.

The new method builds upon a technique called single-cell combinatorial indexed sequencing, which generates DNA libraries for thousands of single cells simultaneously. This approach is particularly important in understanding cancer, as the cells of a tumor can be strikingly diverse.

Single-cell analysis allows the study of cell-to-cell variation within an organ, tissue, or cancerous tumor. The method can now reveal DNA alterations that have emerged in a subset of cells in tumor samples taken from patients with pancreatic cancer.

The team is working to test the single-cell method as a way to find out if some of the cells in a patient's tumor have evolved resistance to a particular chemo drug or targeted therapy. This could potentially lead to more personalised treatment plans for cancer patients.

The adapters in the new method are designed to be compatible with standard sequencing recipes, making it compatible with many different tests. Moreover, custom workflows and primers are no longer required, unlike competing methods.

Andrew Adey and OHSU colleague Ryan M. Mulqueen are authors on licensed patents that cover components of the technologies described in the research. The inventive methods developed and licensed by these researchers at OHSU include techniques related to advanced genomic sequencing and molecular analysis technologies.

The genetic code is written in DNA in a sequence of units, called bases, which are like letters of an alphabet. Sequencing DNA reveals the order of the bases, and it is the first step to understanding the genetic makeup of a cell and whether particular genes are active or silent.

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The research was supported by the National Institutes of Health (grants R01DA047237, R35GM124704, and R01MH113926). This research was published in the journal Nature Biotechnology (DOI: 10.1038/s41587-021-00962-z).

The new method delivers about a ten-fold improvement in the amount of DNA that can be recovered from a single cell for sequencing and interpretation. This improvement will undoubtedly lead to a more comprehensive understanding of how populations of tumor cells evolve and become deadly. The innovation is a significant step towards understanding cancer development and personalised treatment strategies.