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Rats were exposed to 1\u2010ppm AFB1 in feed for 14, 90, and 90\u2009days plus a recovery 60\u2010day, non\u2010exposure period (150\u2010day) timepoint. Isolated liver DNA was exome sequenced. We identified 172 sequence variants across all timepoints, of which 101 were non\u2010synonymous variants. Well\u2010annotated genes carried a diverse set of 29 non\u2010synonymous mutations at 14\u2009days, increasing to 39 mutations at 90\u2009days and then decreasing to 33 mutations following the 60\u2010day recovery. Gene Set Enrichment Analysis conducted on previously reported, available RNA expression data of the same exome sequenced archival samples identified altered transcripts in pathways associated with malignant transformation. These included HALLMARK gene sets associated with cell proliferation (MYC Targets Version 1 and Version 2, E2F targets), cell cycle (G2M checkpoint, mitotic spindle), cell death (apoptosis), and DNA damage (DNA repair, UV response Up, Reactive oxygen species) pathways. DriverNet Impact analysis integrated exome\u2010seq and expression data to reveal somatic mutations in <jats:italic>Mcm8<\/jats:italic>, <jats:italic>Bdp1<\/jats:italic>, and <jats:italic>Cct6a<\/jats:italic> that may drive cancer formation. Connectivity with transcript expression changes identified these genes as the top\u2010ranked candidate driver genes associated with hepatocellular transformation. In conclusion, exome sequencing revealed early somatic mutations that may play a role in cancer cell transformation that are translatable to aflatoxin\u2010induced HCC.<\/jats:p>","DOI":"10.1002\/jat.4463","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T01:11:00Z","timestamp":1678669860000},"page":"1293-1305","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Whole exome and transcript profiling of liver following aflatoxin B1 exposure in rats"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9726-2821","authenticated-orcid":false,"given":"Julie F.","family":"Foley","sequence":"first","affiliation":[{"name":"Division, National Toxicology Program NIEHS  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Elgart","sequence":"additional","affiliation":[{"name":"Molecular Genomics Core Laboratory, Signal Transduction Laboratory, Division of Intramural Research NIEHS  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhiral","family":"Phadke","sequence":"additional","affiliation":[{"name":"Sciome LLC  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Mav","sequence":"additional","affiliation":[{"name":"Sciome LLC  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Tripodi","sequence":"additional","affiliation":[{"name":"Sciome LLC  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2354-9357","authenticated-orcid":false,"given":"Nicholas","family":"Clausen","sequence":"additional","affiliation":[{"name":"Molecular Genomics Core Laboratory, Signal Transduction Laboratory, Division of Intramural Research NIEHS  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine","family":"Weick","sequence":"additional","affiliation":[{"name":"Molecular Genomics Core Laboratory, Signal Transduction Laboratory, Division of Intramural Research NIEHS  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wes","family":"Gladwell","sequence":"additional","affiliation":[{"name":"Molecular Genomics Core Laboratory, Signal Transduction Laboratory, Division of Intramural Research NIEHS  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Gerrish","sequence":"additional","affiliation":[{"name":"Molecular Genomics Core Laboratory, Signal Transduction Laboratory, Division of Intramural Research NIEHS  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruchir","family":"Shah","sequence":"additional","affiliation":[{"name":"Sciome LLC  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. 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