{"doi":"10.1002/1878-0261.13345","title":"A trans‐omics assessment of gene–gene interaction in early‐stage <scp>NSCLC</scp>","abstract":"Epigenome‐wide gene–gene (G × G) interactions associated with non‐small‐cell lung cancer (NSCLC) survival may provide insights into molecular mechanisms and therapeutic targets. Hence, we proposed a three‐step analytic strategy to identify significant and robust G × G interactions that are relevant to NSCLC survival. In the first step, among 49 billion pairs of DNA methylation probes, we identified 175 775 G × G interactions with P Bonferroni ≤ 0.05 in the discovery phase of epigenomic analysis; among them, 15 534 were confirmed with P ≤ 0.05 in the validation phase. In the second step, we further performed a functional validation for these G × G interactions at the gene expression level by way of a two‐phase (discovery and validation) transcriptomic analysis, and confirmed 25 significant G × G interactions enriched in the 6p21.33 and 6p22.1 regions. In the third step, we identified two G × G interactions using the trans‐omics analysis, which had significant ( P ≤ 0.05) epigenetic cis ‐regulation of transcription and robust G × G interactions at both the epigenetic and transcriptional levels. These interactions were cg14391855 × cg23937960 ( β interaction = 0.018, P = 1.87 × 10 −12 ), which mapped to RELA × HLA‐G ( β interaction = 0.218, P = 8.82 × 10 −11 ) and cg08872738 × cg27077312 ( β interaction = −0.010, P = 1.16 × 10 −11 ), which mapped to TUBA1B × TOMM40 ( β interaction =−0.250, P = 3.83 × 10 −10 ). A trans‐omics mediation analysis revealed that 20.3% of epigenetic effects on NSCLC survival were significantly ( P = 0.034) mediated through transcriptional expression. These statistically significant trans‐omics G × G interactions can also discriminate patients with high risk of mortality. In summary, we identified two G × G interactions at both the epigenetic and transcriptional levels, and our findings may provide potential clues for precision treatment of NSCLC.","journal":"Molecular Oncology","year":2022,"id":282915,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.814,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":959329,"name":"Xue Song","orcid":"0000-0002-9305-9161","position":1,"is_corresponding":false},{"id":376163,"name":"Yi Li","orcid":"0000-0002-9976-518X","position":2,"is_corresponding":false},{"id":318176,"name":"Yongyue Wei","orcid":"0000-0002-1132-1796","position":3,"is_corresponding":false},{"id":318159,"name":"Sipeng Shen","orcid":"0000-0003-0436-4736","position":4,"is_corresponding":false},{"id":751165,"name":"Yang Zhao","orcid":"0000-0001-9318-5371","position":5,"is_corresponding":false},{"id":318160,"name":"Dongfang You","orcid":"0000-0002-0856-0323","position":6,"is_corresponding":false},{"id":318169,"name":"Li Su","orcid":"0000-0002-6453-199X","position":7,"is_corresponding":false},{"id":318172,"name":"Maria Moksnes Bjaanæs","orcid":"0000-0001-7126-9064","position":8,"is_corresponding":false},{"id":772717,"name":"Anna Karlsson","orcid":"0000-0003-1131-3726","position":9,"is_corresponding":false},{"id":318174,"name":"Maria Planck","orcid":"0000-0001-7893-6755","position":10,"is_corresponding":false},{"id":14083,"name":"Johan Staaf","orcid":"0000-0001-5254-5115","position":11,"is_corresponding":false},{"id":309114,"name":"Åslaug Helland","orcid":"0000-0002-5520-0275","position":12,"is_corresponding":false},{"id":279361,"name":"Manel Esteller","orcid":"0000-0003-4490-6093","position":13,"is_corresponding":false},{"id":251851,"name":"Hongbing Shen","orcid":"0000-0002-2581-5906","position":14,"is_corresponding":false},{"id":251842,"name":"David C. 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