Bioinformatics Seminars

Bioinformatics Seminar

Time: 3PM
Venue: Zoom Webinar

28 September 2021

Please note special time: 3pm

Integration of multiple CyTOF datasets to untangle the heterogeneity of chronic lymphocytic leukaemia patient responses to venetoclax

Marie Trussart
WEHI Bioinformatics

By detecting over 40 proteins on millions of single cells, mass cytometry or cytometry by Time-Of-Flight CyTOF allows characterisation of tumour populations in individual patients in unprecedented detail. The BCL-2 inhibitor, venetoclax, is an effective treatment for chronic lymphocytic leukaemia (CLL). However, some open questions around the heterogeneity of CLL patients' responses to venetoclax remains unclear as most CyTOF experiments have been performed on a single-run/single datasets containing 20 barcoded samples. Multi-run CyTOF studies of large clinical cohorts including a larger number of patients and increasing drug-treatment doses can provide a deeper understanding of the molecular and cellular changes induced in each patient by the treatment, and precisely how the pressure exerted by venetoclax is manifested at the cellular level to engender resistance in some patients. In this study, we performed mass cytometric profiling (CyTOF) of a large cohort of samples from CLL patients during venetoclax dose escalation and measured changes in 41 regulators of immune cells, cell death, proliferation, cell signalling and cancer-related pathways at the single-cell resolution. To enable the integration of multiple CyTOF datasets (160 samples), we applied CytofRUV that removes batch effects in CyTOF data using replicated reference samples. This allowed us to compare cellular changes in multiple patients and correlate these to clinically relevant outcomes.

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