Extended Data Fig. 1: Collateral lethal target identification in paralogous metabolic pathways.
(a) Most significant focal deletions in chromosomes 1-22, identified by GISTIC2.0, within deleted regions for breast, pancreatic, prostate, hepatocellular cancer, and acute myeloid leukemia (b) Number of metabolic genes found in frequently deleted chromosomal regions that have known paralogs for cancers shown in (a). (c) Number of metabolic gene deletions identified in various cancers that may or may not have known genetic paralog. (d) Identification of paralogous metabolic pathways: Several metabolic enzymes have isoforms encoded by genetic paralogs, for example, Gene X1 and X2. When Gene X2 does not exist or its inhibition is ineffective, redundancy via pathway encoded by Gene Z1, can compensate for loss of Gene X1. To obtain a collateral lethal effect, Gene Z1 encoding the paralogous metabolic pathway must be identified and targeted. (e) Correlation of UQCR11 copy-number with UQCR11 mRNA expression in ovarian cancer tumors from the TCGA HGSOC dataset. Data analyzed using Spearman’s rank correlation test.
