Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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RNA-seq of S. cerevisiae with DOPAC and 4-nitrocatechol to investigate how Artificial Intelligence uncovers human carcinogenic metabolites

ABSTRACT: We have performed paired-end RNA-sequencing on budding yeast (BY4741), exposed to 4-nitrocatechol and 3,4-Dihydroxyphenylacetic acid (DOPAC). These two human metabolites were predicted as potential carcinogens using Metabokiller, an artificial intelligence-driven carcinogenicity predictor. The dataset contains 3 biological conditions, i.e. untreated (NC), DOPAC treated (DP), and 4-nitrocatechol treated (4NC). Two rounds of selection procedures have been introduced. The first selection was for canavanine resistance, and the followed selection was for rapid cell division (inferred using growth assay). The experiment was performed in biological triplicates.

INSTRUMENT(S): Illumina HiSeq 4000

ORGANISM(S): Saccharomyces cerevisiae

SUBMITTER: Gaurav Ahuja

PROVIDER: E-MTAB-11179 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:BackgroundInfections classified as group 1 biological carcinogens include the helminthiases caused by Schistosoma haematobium and Opisthorchis viverrini. The molecular mediators underlying the infection with these parasites and cancer remain unclear. Although carcinogenesis is a multistep process, we have postulated that these parasites release metabolites including oxysterols and estrogen-like metabolites that interact with host cell DNA. How and why the parasite produce/excrete these metabolites remain unclear. A gene encoding a CYP enzyme was identified in schistosomes and opisthorchiids. Therefore, it is reasonable hypothesized that CYP 450 might play a role in generation of pro-inflammatory and potentially carcinogenic compounds produced by helminth parasites such as oxysterols and catechol estrogens. Here, we performed enzymatic assays using several isoforms of CYP 450 as CYP1A1, 2E1 and 3A4 which are involved in the metabolism of chemical carcinogens that have been associated with several cancer. The main aim was the analysis of the role of these enzymes in production of helminth-associated metabolites and DNA-adducts.MethodThe effect of cytochrome P450 enzymes CYP 1A1, 2E1 and 3A4 during the interaction between DNA, glycocholic acid and taurochenodeoxycholate sodium on the formation of DNA-adducts and metabolites associated with urogenital schistosomiasis (UGS) and opisthorchiasis was investigated in vitro. Liquid chromatography/mass spectrometry was used to detect and identify metabolites.Main findingsThrough the enzymatic assays we provide a deeper understanding of how metabolites derived from helminths are formed and the influence of CYP 450. The assays using compounds similar to those previously observed in helminths as glycocholic acid and taurochenodeoxycholate sodium, allowed the detection of metabolites in their oxidized form and their with DNA. Remarkably, these metabolites were previously associated with schistosomiaisis and opisthorchiasis. Thus, in the future, it may be possible to synthesize this type of metabolites through this methodology and use them in cell lines to clarify the carcinogenesis process associated with these diseases.Principal conclusionsMetabolites similar to those detected in helminths are able to interact with DNA in vitro leading to the formation of DNA adducts. These evidences supported the previous postulate that imply helminth-like metabolites as initiators of helminthiases-associated carcinogenesis. Nonetheless, studies including these kinds of metabolites and cell lines in order to evaluate its potential carcinogenic are required.

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RNA-seq of S. cerevisiae with DOPAC and 4-nitrocatechol to investigate how Artificial Intelligence uncovers human carcinogenic metabolites

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