A network-based approach to integrate nutrient microenvironment in the prediction of synthetic lethality in cancer metabolism
Fig 2
Predicted synthetic lethals involving DHFR with thymidine and hypoxanthine in the growth medium.
(a) 4 genetic Minimal Cut Sets (gMCSs) and 2 nutrient-genetic Minimal Cut Sets (ngMCSs) involving DHFR. They were derived from Recon3D under the RPMI1640 growth medium plus thymidine and hypoxanthine; (b) Simplified network of metabolites and enzymes implied in the synthesis of purines and pyrimidines, emphasizing the role of DHFR, Thymidine and Hypoxanthine. Abbreviations: DHF: dihydrofolate; THF: tetrahydrofolate; IMP: inosinic acid; dTMP: 5-Thymidylic acid; DHFR: dihydrofolate reductase; PNP: purine nucleoside phosphorylase; HPRT1: hypoxanthine phosphoribosyltransferase 1; XDH: xanthine dehydrogenase; GMPS: Guanine Monophosphate Synthase; TK1: thymidine kinase 1; TK2: thymidine kinase 2; SLC29A2: solute carrier family 29 member 2.