Fig. 1

Overall workflow and summary of results in each step. The pyrimidine metabolism (KEGG PATHWAY: hsa00240, 100 genes) has been chosen as a starting point and then using comprehensive PPI to extend the pathway to add more proteins that could be potentially related to the pathway in which 69 new proteins can be added. We also added 9 membrane transporters that have been known to be associated with the gemcitabine pharmacologic pathway. 5046 nsSNPs are found to be linked to the 178 genes (100 together with the new 69 and the 9 transporters’ genes). 77 of them are found to be common in Singaporean population. After that, five criteria have been used to prioritize the common SNPs. We did detailed SNP analysis for 15 common nsSNPs that passed at least 3 out of 5 criteria and some borderline SNPs. Finally, after thorough literature review, we selected six SNPs to be genotyped in the NSCLC Singaporean patient cohort. PPI: Protein-protein interaction, SGVP: Singaporean Genome Variation Project