TY - JOUR TI - Comprehensive and unbiased multiparameter high-throughput screening by compaRe finds effective and subtle drug responses in AML models AU - Chalabi Hajkarim, Morteza AU - Karjalainen, Ella AU - Osipovitch, Mikhail AU - Dimopoulos, Konstantinos AU - Gordon, Sandra L AU - Ambri, Francesca AU - Rasmussen, Kasper Dindler AU - Grønbæk, Kirsten AU - Helin, Kristian AU - Wennerberg, Krister AU - Won, Kyoung-Jae A2 - Walczak, Aleksandra M A2 - Tan, Aik Choon VL - 11 PY - 2022 DA - 2022/02/15 SP - e73760 C1 - eLife 2022;11:e73760 DO - 10.7554/eLife.73760 UR - https://doi.org/10.7554/eLife.73760 AB - Large-scale multiparameter screening has become increasingly feasible and straightforward to perform thanks to developments in technologies such as high-content microscopy and high-throughput flow cytometry. The automated toolkits for analyzing similarities and differences between large numbers of tested conditions have not kept pace with these technological developments. Thus, effective analysis of multiparameter screening datasets becomes a bottleneck and a limiting factor in unbiased interpretation of results. Here we introduce compaRe, a toolkit for large-scale multiparameter data analysis, which integrates quality control, data bias correction, and data visualization methods with a mass-aware gridding algorithm-based similarity analysis providing a much faster and more robust analyses than existing methods. Using mass and flow cytometry data from acute myeloid leukemia and myelodysplastic syndrome patients, we show that compaRe can reveal interpatient heterogeneity and recognizable phenotypic profiles. By applying compaRe to high-throughput flow cytometry drug response data in AML models, we robustly identified multiple types of both deep and subtle phenotypic response patterns, highlighting how this analysis could be used for therapeutic discoveries. In conclusion, compaRe is a toolkit that uniquely allows for automated, rapid, and precise comparisons of large-scale multiparameter datasets, including high-throughput screens. KW - high-throughput screening KW - high-content screening KW - drug dose response analysis KW - AML KW - single cell KW - drug discovery KW - sample clustering JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -