Cell Pathology Revealed by Single Cell Genotype-phenotype Mapping

Speaker

Abstract

Cancers are genetic diseases driven by recurrent sets of somatic mutations. Different mutations associate statistically with distinct disease risks and can therefore be useful prognostic markers. But, for the majority the underlying biological mechanisms are unknown. Uncovering the physiological consequences of these mutations is important as this could identify novel targets for treatment. However, since most cancers are polyclonal tissues, multiple distinct mutations contribute to the tumor behavior and linking genotype to phenotype is complicated through the convolution of these clones. Methods with single cell resolution can address this issue and  through simultaneous measurements of genotype and phenotype cause and effect can be linked.

In my talk I present DAb-seq, our new droplet microfluidic sequencing method that profiles single-cell genotypes through multiplexed PCR panels and immunophenotypes through DNA tagged antibody panels. I highlight the unique capabilities of DAb-seq with case studies on leukemia and samples from patients with HIV. As DAb-seq is purposely designed modular we are actively extending the approach to access even richer information in the future.

Learning Objectives:

1. Explain the inherent advantages of high throughput single cell methods.

2. Discuss why joint measurements of genotype and phenotype important to understand genetic diseases.

3. Discuss why genotype phenotype mapping can be useful in the study of infectious diseases.


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