Extended Data Fig. 8: MM-preferential dependencies with distinct vs. overlapping roles in MM vs. other hematologic neoplasias or solid tumors.
a, Heat map for MM-preferential dependencies, summarizing their potential roles as preferential dependencies for other malignancies. Color coding indicates the difference in average CERES score for each gene in a given tumor type vs. all others: black/blue or red/orange denote FDR < 0.05 and lower or higher, respectively, average CERES scores for a given gene in the respective neoplasia vs. all other cancer types. White denotes FDR > 0.05. b-c, t-SNE plots of cell lines (depicted as dots), from MM, leukemias, lymphomas or other neoplasias, clustered according to RNA-Seq profiles b, or CERES scores c, for MM-preferential dependencies. RPKM data in b from CCLE [2018] for lines with matching 20Q4v2 CERES scores (N = 15, 33, 16, 505 lines, respectively). In c, N = 19, 44, 20, 706 lines, respectively (20Q4v2). d, Numbers of CRISPR-defined preferential dependencies (y-axis; identified based on the same criteria applied for MM) vs. number of lines for each indicated tumor type (x-axis). e, Volcano plot of -log10FDR (Limma t-test) for comparison of CERES scores in MM vs non-MM hematopoietic cell lines (y-axis) vs. difference in average CERES scores in MM vs. non-MM cell hematopoietic lines (x-axis). MM-preferential dependencies (identified in this study by comparison of MM vs. all non-MM cell lines) are depicted in red and orange, respectively, if they did vs. did not exhibit significantly lower CERES scores in MM compared with non-MM hematopoietic lines. f-h, Dependencies with differential role in MM vs. solid tumors or vs. B-cell lymphomas. Volcano plots for comparisons of CERES scores in MM lines (N = 19) vs. f, all non-MM cell lines, from both hematologic malignancies and solid tumors (N = 768; also see Supplementary Table 1); g, only solid tumor cell lines (N = 701); h, B cell lymphoma lines (N = 13) (x-axis: difference in average CERES scores between respective groups; y-axis: -log10FDR, Limma t-test). Red dots in each plot indicate genes satisfying criteria for more pronounced essentiality in MM compared with the respective groups of cell lines; i, Venn diagram highlighting genes with differential role in MM vs. solid tumors or B-cell lymphomas, based on panels f-h. j, CERES scores for genes that do not meet criteria for MM-preferential dependencies (comparison of MM vs. all other non-MM lines), but are more essential in MM vs. solid tumors or B-cell lymphomas, based on panels f-h.
