{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T16:33:31Z","timestamp":1769186011685,"version":"3.49.0"},"reference-count":74,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Fundamental Research Funds for the Central Universities","award":["21623335"],"award-info":[{"award-number":["21623335"]}]},{"name":"The Science and Technology Projects in Guangzhou","award":["2024A04J4125"],"award-info":[{"award-number":["2024A04J4125"]}]},{"name":"The Youth S&T Talent Support Programme of Guangdong Provincial Association for Science and Technology","award":["11625223"],"award-info":[{"award-number":["11625223"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-AIDS-defining cancers (NADCs) have emerged as an increasingly prominent cause of non-AIDS-related morbidity and mortality among people living with HIV (PLWH). However, the scarcity of NADC clinical samples, compounded by privacy and security constraints, continues to present formidable obstacles to advancing pathological and clinical investigations. In this study, we adopted a joint analysis strategy and deeply integrated and analyzed transcriptomic data from 12,486 PLWH and cancer patients to systematically identify potential key regulators for 23 NADCs. This effort culminated in NADCdb\u2014a database specifically engineered for NADC pathological exploration, structured around three mechanistic frameworks rooted in the interplay of immunosuppression, chronic inflammation, carcinogenic viral infections, and HIV-derived oncogenic pathways. The \u201crNADC\u201d module performed risk assessment by prioritizing genes with aberrant expression trajectories, deploying bidirectional stepwise regression coupled with logistic modeling to stratify the risks for 21 NADCs. The \u201cdNADC\u201d module, synergized patients\u2019 dysregulated genes with their regulatory networks, using Random Forest (RF) and Conditional Inference Trees (CITs) to identify pathogenic drivers of NADCs, with an accuracy exceeding 75% (in the external validation cohort, the prediction accuracy of the HIV-associated clear cell renal cell carcinoma model exceeded 90%). Meanwhile, \u201ciPredict\u201d identified 1905 key immune biomarkers for 16 NADCs based on the distinct immune statuses of patients. Importantly, we conducted multi-dimensional profiling of these key determinants, including in-depth functional annotations, phenotype correlations, protein\u2013protein interaction (PPI) networks, TF-miRNA-target regulatory networks, and drug prediction, to deeply dissect their mechanistic roles in NADC pathogenesis. In summary, NADCdb serves as a novel, centralized resource that integrates data and provides analytical frameworks, offering fresh perspectives and a valuable platform for the scientific exploration of NADCs.<\/jats:p>","DOI":"10.3390\/ijms27031169","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T14:58:40Z","timestamp":1769180320000},"page":"1169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["NADCdb: A Joint Transcriptomic Database for Non-AIDS-Defining Cancer Research in HIV-Positive Individuals"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5066-2720","authenticated-orcid":false,"given":"Jiajia","family":"Xuan","sequence":"first","affiliation":[{"name":"MOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunhua","family":"Xiao","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Runhao","family":"Luo","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yonglei","family":"Luo","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0503-9492","authenticated-orcid":false,"given":"Qing-Yu","family":"He","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0378-255X","authenticated-orcid":false,"given":"Wanting","family":"Liu","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101613","DOI":"10.1016\/j.eclinm.2022.101613","article-title":"Incidence and mortality of non-AIDS-defining cancers among people living with HIV: A systematic review and meta-analysis","volume":"52","author":"Yuan","year":"2022","journal-title":"EClinicalMedicine"},{"key":"ref_2","unstructured":"UNAIDS (2025). Global HIV & AIDS Statistics\u2014Fact Sheet; UNAIDS 2025 Epidemiological Estimates, UNAIDS."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1056\/NEJMra1615896","article-title":"HIV-Associated Cancers and Related Diseases","volume":"378","author":"Yarchoan","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1097\/QAD.0000000000000071","article-title":"Malignancies in HIV\/AIDS: From epidemiology to therapeutic challenges","volume":"28","author":"Rubinstein","year":"2014","journal-title":"Aids"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1097\/QAD.0b013e3283112b77","article-title":"HIV-induced immunodeficiency and mortality from AIDS-defining and non-AIDS-defining malignancies","volume":"22","author":"Monforte","year":"2008","journal-title":"Aids"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S0140-6736(14)60604-8","article-title":"Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): A multicohort collaboration","volume":"384","author":"Smith","year":"2014","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e495","DOI":"10.1016\/S2352-3018(17)30125-X","article-title":"Cancer risk in HIV-infected people in the USA from 1996 to 2012: A population-based, registry-linkage study","volume":"4","author":"Shiels","year":"2017","journal-title":"Lancet HIV"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e647","DOI":"10.1016\/S2352-3018(18)30179-6","article-title":"Incidence of first and second primary cancers diagnosed among people with HIV, 1985\u20132013: A population-based, registry linkage study","volume":"5","author":"Hessol","year":"2018","journal-title":"Lancet HIV"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/S1470-2045(24)00189-X","article-title":"Cancer risk in people living with HIV and solid organ transplant recipients: A systematic review and meta-analysis","volume":"25","author":"Jin","year":"2024","journal-title":"Lancet Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e240","DOI":"10.1016\/S1470-2045(21)00137-6","article-title":"The effect of non-AIDS-defining cancers on people living with HIV","volume":"22","author":"Chiao","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_11","first-page":"69","article-title":"Malignancies in people living with HIV","volume":"24","author":"Zhou","year":"2022","journal-title":"AIDS Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/QAI.0000000000001554","article-title":"Inflammation-Related Morbidity and Mortality Among HIV-Positive Adults: How Extensive Is It?","volume":"77","author":"Hart","year":"2018","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"42","DOI":"10.47672\/ejhs.522","article-title":"Mechanism of Increased Cancer Risk in HIV","volume":"5","author":"Okuma","year":"2020","journal-title":"Eur. J. Health Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1097\/CCO.0b013e328355e131","article-title":"HIV infection, aging, and immune function: Implications for cancer risk and prevention","volume":"24","author":"Dubrow","year":"2012","journal-title":"Curr. Opin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1053\/j.seminoncol.2015.09.011","article-title":"Cancer prevention in HIV-infected populations","volume":"43","author":"Goncalves","year":"2016","journal-title":"Semin. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.idc.2024.06.007","article-title":"Cancer in People with HIV","volume":"38","author":"Odeny","year":"2024","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1097\/COH.0000000000000025","article-title":"Factors contributing to risk for cancer among HIV-infected individuals, and evidence that earlier combination antiretroviral therapy will alter this risk","volume":"9","author":"Borges","year":"2014","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3369","DOI":"10.1016\/j.csbj.2023.06.010","article-title":"Systems crosstalk between antiviral response and cancerous pathways via extracellular vesicles in HIV-1-associated colorectal cancer","volume":"21","author":"Chen","year":"2023","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1002\/cam4.4853","article-title":"Identification of unique transcriptomic signatures and key genes through RNA sequencing and integrated WGCNA and PPI network analysis in HIV infected lung cancer","volume":"12","author":"Wu","year":"2023","journal-title":"Cancer Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.omtn.2022.06.002","article-title":"Comprehensive RNA-seq reveals molecular changes in kidney malignancy among people living with HIV","volume":"29","author":"Bao","year":"2022","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"13128","DOI":"10.1038\/s41598-018-31572-6","article-title":"Molecular Changes of Lung Malignancy in HIV Infection","volume":"8","author":"Zheng","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Curty, G., Beckerle, G.A., I\u00f1iguez, L.P., Furler, R.L., de Carvalho, P.S., Marston, J.L., Champiat, S., Heymann, J.J., Ormsby, C.E., and Reyes-Ter\u00e1n, G. (2020). Human Endogenous Retrovirus Expression Is Upregulated in the Breast Cancer Microenvironment of HIV Infected Women: A Pilot Study. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.553983"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Zhou, T.T., Sun, J.J., Tang, L.D., Yuan, Y., Wang, J.Y., and Zhang, L. (2023). Potential diagnostic markers and therapeutic targets for rheumatoid arthritis with comorbid depression based on bioinformatics analysis. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1007624"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"112064","DOI":"10.1016\/j.intimp.2024.112064","article-title":"Identification of shared potential diagnostic markers in asthma and depression through bioinformatics analysis and machine learning","volume":"133","author":"Jiang","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Zhang, T., Geng, M., Li, X., Gu, Y., Zhao, W., Ning, Q., Zhao, Z., Wang, L., Zhang, H., and Zhang, F. (2024). Identification of Oxidative Stress-Related Biomarkers for Pain-Depression Comorbidity Based on Bioinformatics. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25158353"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: Kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1111\/joim.12722","article-title":"Mechanisms regulating expansion of CD8+ T cells during HIV-1 infection","volume":"283","author":"Nasi","year":"2018","journal-title":"J. Intern. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"15035","DOI":"10.1038\/nrdp.2015.35","article-title":"HIV infection","volume":"1","author":"Deeks","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_29","first-page":"682","article-title":"The enduring tale of T cells in HIV immunopathogenesis","volume":"138","author":"Vajpayee","year":"2013","journal-title":"Indian J. Med. Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Langfelder, P., and Horvath, S. (2008). WGCNA: An R package for weighted correlation network analysis. BMC Bioinform., 9.","DOI":"10.1186\/1471-2105-9-559"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"eabd6991","DOI":"10.1126\/sciadv.abd6991","article-title":"Predicting tissue-specific gene expression from whole blood transcriptome","volume":"7","author":"Basu","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1093\/bioinformatics\/btn615","article-title":"AmiGO: Online access to ontology and annotation data","volume":"25","author":"Carbon","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein-protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1016\/j.cell.2017.10.049","article-title":"A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles","volume":"171","author":"Subramanian","year":"2017","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1093\/bib\/bbt085","article-title":"Transcription factor and microRNA co-regulatory loops: Important regulatory motifs in biological processes and diseases","volume":"16","author":"Zhang","year":"2015","journal-title":"Brief. Bioinform."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1002\/bies.200800212","article-title":"The interplay between transcription factors and microRNAs in genome-scale regulatory networks","volume":"31","author":"Martinez","year":"2009","journal-title":"Bioessays"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.celrep.2016.12.019","article-title":"Pan-cancer Immunogenomic Analyses Reveal Genotype-Immunophenotype Relationships and Predictors of Response to Checkpoint Blockade","volume":"18","author":"Charoentong","year":"2017","journal-title":"Cell Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4200","DOI":"10.1093\/bioinformatics\/btz210","article-title":"TISIDB: An integrated repository portal for tumor-immune system interactions","volume":"35","author":"Ru","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Borgia, M., Dal Bo, M., and Toffoli, G. (2021). Role of Virus-Related Chronic Inflammation and Mechanisms of Cancer Immune-Suppression in Pathogenesis and Progression of Hepatocellular Carcinoma. Cancers, 13.","DOI":"10.3390\/cancers13174387"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Mu, W., Patankar, V., Kitchen, S., and Zhen, A. (2024). Examining Chronic Inflammation, Immune Metabolism, and T Cell Dysfunction in HIV Infection. Viruses, 16.","DOI":"10.3390\/v16020219"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e177310","DOI":"10.1172\/JCI177310","article-title":"The tumor microenvironment of non-small cell lung cancer impairs immune cell function in people with HIV","volume":"135","author":"Desai","year":"2025","journal-title":"J. Clin. Investig."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Omar, A., Marques, N., and Crawford, N. (2024). Cancer and HIV: The Molecular Mechanisms of the Deadly Duo. Cancers, 16.","DOI":"10.3390\/cancers16030546"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Swase, T.D., Fasogbon, I.V., Eseoghene, I.J., Etukudo, E.M., Mbina, S.A., Joan, C., Dangana, R.S., Anyanwu, C., Vandu, C.D., and Agbaje, A.B. (2025). The impact of HPV\/HIV co-infection on immunosuppression, HPV genotype, and cervical cancer biomarkers. BMC Cancer, 25.","DOI":"10.1186\/s12885-025-13516-2"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Tolomeo, M., Tolomeo, F., and Cascio, A. (2025). The Complex Interactions Between HIV-1 and Human Host Cell Genome: From Molecular Mechanisms to Clinical Practice. Int. J. Mol. Sci., 26.","DOI":"10.20944\/preprints202503.1620.v1"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"D991","DOI":"10.1093\/nar\/gks1193","article-title":"NCBI GEO: Archive for functional genomics data sets\u2014Update","volume":"41","author":"Barrett","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"D711","DOI":"10.1093\/nar\/gky964","article-title":"ArrayExpress update\u2014From bulk to single-cell expression data","volume":"47","author":"Athar","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_47","unstructured":"WHO (2021). WHO Guidelines Approved by the Guidelines Review Committee. Consolidated Guidelines on HIV Prevention, Testing, Treatment, Service Delivery and Monitoring: Recommendations for a Public Health Approach, World Health Organization."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1093\/bioinformatics\/btn647","article-title":"arrayQualityMetrics\u2014A bioconductor package for quality assessment of microarray data","volume":"25","author":"Kauffmann","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1093\/bioinformatics\/btq431","article-title":"A framework for oligonucleotide microarray preprocessing","volume":"26","author":"Carvalho","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/bioinformatics\/btn224","article-title":"lumi: A pipeline for processing Illumina microarray","volume":"24","author":"Du","year":"2008","journal-title":"Bioinformatics"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1093\/bioinformatics\/btw354","article-title":"MultiQC: Summarize analysis results for multiple tools and samples in a single report","volume":"32","author":"Ewels","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: A fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: An efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"D942","DOI":"10.1093\/nar\/gkac1071","article-title":"GENCODE: Reference annotation for the human and mouse genomes in 2023","volume":"51","author":"Frankish","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e71","DOI":"10.1093\/nar\/gkv1507","article-title":"TCGAbiolinks: An R\/Bioconductor package for integrative analysis of TCGA data","volume":"44","author":"Colaprico","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1038\/ng.2764","article-title":"The Cancer Genome Atlas Pan-Cancer analysis project","volume":"45","author":"Weinstein","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1126\/science.aaz1776","article-title":"The GTEx Consortium atlas of genetic regulatory effects across human tissues","volume":"369","author":"Consortium","year":"2020","journal-title":"Science"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/s41587-020-0546-8","article-title":"Visualizing and interpreting cancer genomics data via the Xena platform","volume":"38","author":"Goldman","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"180015","DOI":"10.1038\/sdata.2018.15","article-title":"ImmPort, toward repurposing of open access immunological assay data for translational and clinical research","volume":"5","author":"Bhattacharya","year":"2018","journal-title":"Sci. Data"},{"key":"ref_61","unstructured":"Team, R.C. (2023). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"D566","DOI":"10.1093\/nar\/gku1126","article-title":"HIV-1, human interaction database: Current status and new features","volume":"43","author":"Fu","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_63","first-page":"18","article-title":"Classification and Regression by randomForest","volume":"2","year":"2002","journal-title":"R. News"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1198\/106186006X133933","article-title":"Unbiased recursive partitioning: A conditional inference framework","volume":"15","author":"Hothorn","year":"2006","journal-title":"J. Comput. Graph. Stat."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v033.i01","article-title":"Regularization Paths for Generalized Linear Models via Coordinate Descent","volume":"33","author":"Friedman","year":"2010","journal-title":"J. Stat. Softw."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"D380","DOI":"10.1093\/nar\/gkx1013","article-title":"TRRUST v2: An expanded reference database of human and mouse transcriptional regulatory interactions","volume":"46","author":"Han","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.gpb.2019.09.006","article-title":"hTFtarget: A Comprehensive Database for Regulations of Human Transcription Factors and Their Targets","volume":"18","author":"Zhang","year":"2020","journal-title":"Genom. Proteom. Bioinform."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"D97","DOI":"10.1093\/nar\/gkaa995","article-title":"GRNdb: Decoding the gene regulatory networks in diverse human and mouse conditions","volume":"49","author":"Fang","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"D222","DOI":"10.1093\/nar\/gkab1079","article-title":"miRTarBase update 2022: An informative resource for experimentally validated miRNA-target interactions","volume":"50","author":"Huang","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"D1003","DOI":"10.1093\/nar\/gkac888","article-title":"Genenames.org: The HGNC resources in 2023","volume":"51","author":"Seal","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"D333","DOI":"10.1093\/nar\/gkab825","article-title":"RNALocate v2.0: An updated resource for RNA subcellular localization with increased coverage and annotation","volume":"50","author":"Cui","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"eaav1741","DOI":"10.1126\/science.aav1741","article-title":"The biochemical basis of microRNA targeting efficacy","volume":"366","author":"McGeary","year":"2019","journal-title":"Science"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"D318","DOI":"10.1093\/nar\/gkae1081","article-title":"TransmiR v3.0: An updated transcription factor-microRNA regulation database","volume":"53","author":"Liang","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Zhou","year":"2019","journal-title":"Nat. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1169\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T14:58:55Z","timestamp":1769180335000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1169"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,23]]},"references-count":74,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["ijms27031169"],"URL":"https:\/\/doi.org\/10.3390\/ijms27031169","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,23]]}}}