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Experiment Overview

Repository ID: FR-FCM-Z3DP Experiment name: High-throughput flow cytometry of an AML human patient MIFlowCyt score: 27.00%
Primary researcher: Morteza Chalabi PI/manager: Morteza Chalabi Uploaded by: Morteza Chalabi
Experiment dates: 2018-01-01 - 2021-01-01 Dataset uploaded: Jan 2021 Last updated: Jan 2021
Keywords: [high throughput flow cytometry] Manuscripts:
Organizations: BRIC – University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, (Denmark)
Purpose: COMPARE, an ultra-fast and robust suite for multiparametric screening, identifies phenotypic drug responses in acute myeloid leukemia
Conclusion: We show that COMPARE can effectively circumvent batch effects in multidimensional screening data while showing remarkably fast clustering. Using COMPARE to analyze high-throughput flow cytometry screening of AML cells, we successfully removed various biases and grouped drugs based on their responses. COMPARE effectively revealed that groups of drugs showed similar responses even though their known mechanisms are different from each other. COMPARE was sensitive enough to capture subtle changes in drug responses. We further applied COMPARE to 25 clinical flow cytometry data sets representing AML and myelodysplastic syndrome (MDS) patients. Without prior knowledge, COMPARE could effectively group the samples based on the disease with indications that the grouping also linked to clinical outcome. Thus we conclude that COMPARE is a useful tool for exploring complex multiparametric datasets and to help interpretation of drug responses.
Comments: Mononuclear cells were isolated from a donated human bone marrow aspirate from an AML patient. The cells were treated with a library of 40 chemotherapy and immunotherapy antineoplastic agents in a seven-point concentration range for 72 h. Cells were subsequently incubated with fluorescently labeled antibodies targeting 11 informative cell surface proteins in 8 fluorescence channels. Samples were read using a high-throughput flow cytometer (iQue Screener Plus, Intellicyt). The uploaded fcs files are after compensation, signal drift and cell viability drift corrections. In case of using COMPARE-suite to reproduce the result of the paper, please start from the 5th module as follows: (1) we used these channels throughout the analysis: SSC-H,VL1-H,VL6-H,BL1-H,BL3-H,BL5-H,RL1-H (2) we set n = 3 in the 5th module, (3) we removed Well_4_G21 from Annotation.txt as a negative control outlier detected by the 7th module, (4) we set nn = 5 in the 8th module
Funding: This work was supported through a centre grant from the Novo Nordisk Foundation (Novo Nordisk Foundation Center for Stem Cell Biology, DanStem; Grant Number NNF17CC0027852) and is also part of the Danish Research Center for Precision Medicine in Blood Cancers funded by the Danish Cancer Society (Grant number R223‐A13071) and Greater Copenhagen Health Science Partners.
Quality control: FCS collection for software testing
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