Exploring the value of oligonucleotide antibody-pair based proteomics in cancer cell lines

Cancer genome alterations that cause cancer cells to grow also confer vulnerabilities, which normal cells lack. The challenge is that, for the majority of cancers, we do not understand the relationship between the genetic alterations and the dependencies they cause. To solve this problem, we are creating a Cancer Dependency Map (DepMap) by systematically identifying genetic dependencies and small molecule sensitivities as well as discovering the biomarkers that predict them. However, we are still in the early stages of having a complete map and there are many dependencies and drug vulnerabilities that are not explained by any of the omics features. Using the antibody-based barcoding Olink technology, we profiled 164 cancer cell lines and compared results to previous MS proteomics. Our initial quality control analysis indicated that Olink to mRNA correlation, in the cell lines, was higher than MS data sets. Using Olink technology, we were able to detect low abundance proteins that might have been missed with MS proteomics. Furthermore, in preliminary analysis we were able to show expected results of dependencies associated with protein expression, and additional investigation with genomic correlations is ongoing. This new proteomics platform will help make progress towards the identification of the landscape of cancer vulnerabilities and create a roadmap for cancer therapeutics.

 

Learning Objectives