In many cases Loewe analyses found significant synergistic as well as antagonistic effects in a cell line at different concentrations of a tested drug combination. Four combinations were found synergistic/antagonistic specifically to the parental (harboring KRAS or BRAF mutation) cell line of the corresponding iso-genic cell lines pair.ĬOMBIA offers considerable improvements over established software for synergy analysis such as MacSynergy TM II as it includes both Bliss (independence) and Loewe (additivity) analyses, together with a tailored non-parametric statistical analysis employing heteroscedasticity, controlled resampling, and global (omnibus) testing. Frequently, concentration dependent but mutation independent joint Bliss and Loewe synergy/antagonism was found statistically significant. In our experiments iso-genic pairs of cell lines were used, differing only with respect to a single clinically important KRAS or BRAF mutation. We analyzed survival effects for 15 different pairs of clinically relevant anti-cancer drugs in three iso-genic pairs of human colorectal cancer carcinoma cell lines, by applying for the first time our novel software (R package) called COMBIA. Received: MaAccepted: SeptemPublished: October 19, 2017 Keywords: synergy analysis combinations iso-genic COMBIA R package Gustafsson 1ġDepartment of Medical Sciences, Cancer Pharmacology, and Computational Medicine, Uppsala University Academic Hospital, Uppsala, SwedenĢDepartment of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, SwedenģCurrent/Present address: Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden Muhammad Kashif 1, 3, Claes Andersson 1, Sharmineh Mansoori 1, Rolf Larsson 1, Peter Nygren 2 and Mats G.
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