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To address this, we designed a hybrid pipeline, disease-related lncRNA\u2013miRNA\u2013mRNA regulatory axis prediction from multiomics (DLRAPom), to identify risk biomarkers and disease-related lncRNA\u2013miRNA\u2013mRNA regulatory axes by adding a novel machine learning model on the basis of conventional analysis and combining experimental validation. The pipeline consists of four parts, including selecting hub biomarkers by conventional bioinformatics analysis, discovering the most essential protein-coding biomarkers by a novel machine learning model, extracting the key lncRNA\u2013miRNA\u2013mRNA axis and validating experimentally. Our study is the first one to propose a new pipeline predicting the interactions between lncRNA and miRNA and mRNA by combining WGCNA and XGBoost. Compared with the methods reported previously, we developed an Optimized XGBoost model to reduce the degree of overfitting in multiomics data, thereby improving the generalization ability of the overall model for the integrated analysis of multiomics data. With applications to gestational diabetes mellitus (GDM), we predicted nine risk protein-coding biomarkers and some potential lncRNA\u2013miRNA\u2013mRNA regulatory axes, which all correlated with GDM. In those regulatory axes, the MALAT1\/hsa-miR-144-3p\/IRS1 axis was predicted to be the key axis and was identified as being associated with GDM for the first time. In short, as a flexible pipeline, DLRAPom can contribute to molecular pathogenesis research of diseases, effectively predicting potential disease-related noncoding RNA regulatory networks and providing promising candidates for functional research on disease pathogenesis.<\/jats:p>","DOI":"10.1093\/bib\/bbac046","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T12:10:23Z","timestamp":1643631023000},"source":"Crossref","is-referenced-by-count":11,"title":["DLRAPom: a hybrid pipeline of Optimized XGBoost-guided integrative multiomics analysis for identifying targetable disease-related lncRNA\u2013miRNA\u2013mRNA regulatory axes"],"prefix":"10.1093","volume":"23","author":[{"given":"Chen","family":"Shen","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Forensic Medicine, Academy of Forensic Science; Key Laboratory of National Ministry of Health for Forensic Sciences, School of Medicine & Forensics, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyu","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of National Ministry of Health for Forensic Sciences, School of Medicine & Forensics, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, the Second Affiliated Hospital, Xi\u2019an Jiaotong University, Xi\u2019an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Ninth Hospital of Xi\u2019an City, Xi\u2019an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of National Ministry of Health for Forensic Sciences, School of Medicine & Forensics, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongsheng","family":"Gui","sequence":"additional","affiliation":[{"name":"Center for Behavior Health and Psychiatry Research, Henry Ford Health System, Detroit, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Han","sequence":"additional","affiliation":[{"name":"Key Laboratory of National Ministry of Health for Forensic Sciences, School of Medicine & Forensics, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiying","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of National Ministry of Health for Forensic Sciences, School of Medicine & Forensics, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenpei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of National Ministry of Health for Forensic Sciences, School of Medicine & Forensics, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochen","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of National Ministry of Health for Forensic Sciences, School of Medicine & Forensics, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Qilu Hospital of Shandong University, Ji\u2019nan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangwei","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Genetics, School of Medicine & Forensics, Shanxi Medical University, Taiyuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5135-3277","authenticated-orcid":false,"given":"Fanglin","family":"Guan","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Forensic Medicine, Academy of Forensic Science; 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