{"doi":"10.3390/biom11030383","title":"Parallel Multi-Omics in High-Risk Subjects for the Identification of Integrated Biomarker Signatures of Type 1 Diabetes","abstract":"BACKGROUND: Biomarkers are crucial for detecting early type-1 diabetes (T1D) and preventing significant β-cell loss before the onset of clinical symptoms. Here, we present proof-of-concept studies to demonstrate the potential for identifying integrated biomarker signature(s) of T1D using parallel multi-omics. METHODS: = 4 + 4) was subjected to parallel unlabeled proteomics, metabolomics, lipidomics, and transcriptomics. The integrated dataset was analyzed using Ingenuity Pathway Analysis (IPA) software for disturbances in the at-risk subjects compared to controls. RESULTS: The final quadra-omics dataset contained 2292 proteins, 328 miRNAs, 75 metabolites, and 41 lipids that were detected in all samples without exception. Disease/function enrichment analyses consistently indicated increased activation, proliferation, and migration of CD4 T-lymphocytes and macrophages. Integrated molecular network predictions highlighted central involvement and activation of NF-κB, TGF-β, VEGF, arachidonic acid, and arginase, and inhibition of miRNA Let-7a-5p. IPA-predicted candidate biomarkers were used to construct a putative integrated signature containing several miRNAs and metabolite/lipid features in the at-risk subjects. CONCLUSIONS: Preliminary parallel quadra-omics provided a comprehensive picture of disturbances in high-risk T1D subjects and highlighted the potential for identifying associated integrated biomarker signatures. With further development and validation in larger cohorts, parallel multi-omics could ultimately facilitate the classification of T1D progressors from non-progressors.","journal":"Biomolecules","year":2021,"id":167758,"datarank":0.9904495488377347,"base_score":3.4657359027997265,"endowment":3.4657359027997265,"self_citation_contribution":0.519860385419959,"citation_network_contribution":0.4705891634177756,"self_endowment_contribution":0.519860385419959,"citer_contribution":0.4705891634177756,"corpus_percentile":null,"corpus_rank":null,"citation_count":31,"citer_count":23,"citers_with_citation_signal":18,"citers_with_endowment":18,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8689,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":434279,"name":"Luis Felipe Álvarez-Hernández","orcid":"0000-0002-0580-6463","position":1,"is_corresponding":false},{"id":262804,"name":"Ernesto Nakayasu","orcid":"0000-0002-4056-2695","position":2,"is_corresponding":false},{"id":255022,"name":"Carrie Nicora","orcid":"0000-0003-2461-9548","position":3,"is_corresponding":false},{"id":324027,"name":"Charles Ansong","orcid":"0000-0001-5793-8559","position":4,"is_corresponding":false},{"id":88852,"name":"Michael J. Muehlbauer","orcid":"0000-0003-1501-0706","position":5,"is_corresponding":false},{"id":88787,"name":"James R. Bain","orcid":"0000-0002-8917-9187","position":6,"is_corresponding":false},{"id":459067,"name":"Ciara Myer","orcid":"0000-0002-2668-8048","position":7,"is_corresponding":false},{"id":459071,"name":"Sanjoy K. Bhattacharya","orcid":"0000-0003-3759-647X","position":8,"is_corresponding":false},{"id":342810,"name":"Péter Buchwald","orcid":"0000-0003-2732-8180","position":9,"is_corresponding":false},{"id":434282,"name":"Midhat H. Abdulreda","orcid":"0000-0002-0146-5876","position":10,"is_corresponding":false},{"id":450956,"name":"Óscar Garnica","orcid":"0000-0001-5064-2587","position":0,"is_corresponding":true}],"reference_count":117,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:45:58.359801Z","pmid":"33806609","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}