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Therefore, we profiled and integrated the DNA methylome, mRNAs, and microRNAs to identify molecular changes associated with sarcoidosis and disease progression that might illuminate underlying mechanisms of disease and potential biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Bronchoalveolar lavage cells from 64 sarcoidosis subjects and 16 healthy controls were used. DNA methylation was profiled on Illumina HumanMethylationEPIC arrays, mRNA by RNA-sequencing, and miRNAs by small RNA-sequencing. Linear models were fit to test for effect of sarcoidosis diagnosis and progression phenotype, adjusting for age, sex, smoking, and principal components of the data. We built a supervised multi-omics model using a subset of features from each dataset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified 1,459 CpGs, 64 mRNAs, and five miRNAs associated with sarcoidosis versus controls and four mRNAs associated with disease progression. Our integrated model emphasized the prominence of the PI3K\/AKT1 pathway, which is important in T cell and mTOR function. Novel immune related genes and miRNAs including\n                      <jats:italic>LYST<\/jats:italic>\n                      ,\n                      <jats:italic>RGS14<\/jats:italic>\n                      ,\n                      <jats:italic>SLFN12L<\/jats:italic>\n                      , and hsa-miR-199b-5p, distinguished sarcoidosis from controls. Our integrated model also demonstrated differential expression\/methylation of\n                      <jats:italic>IL20RB<\/jats:italic>\n                      ,\n                      <jats:italic>ABCC11<\/jats:italic>\n                      ,\n                      <jats:italic>SFSWAP<\/jats:italic>\n                      ,\n                      <jats:italic>AGBL4<\/jats:italic>\n                      , miR-146a-3p, and miR-378b between non-progressive and progressive sarcoidosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Leveraging the DNA methylome, transcriptome, and miRNA-sequencing in sarcoidosis BAL cells, we detected widespread molecular changes associated with disease, many which are involved in immune response. These molecules may serve as diagnostic\/prognostic biomarkers and\/or drug targets, although future testing is required for confirmation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12931-024-02919-7","type":"journal-article","created":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T16:02:43Z","timestamp":1722355363000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Multi-omic signatures of sarcoidosis and progression in bronchoalveolar lavage cells"],"prefix":"10.1186","volume":"25","author":[{"given":"Iain R.","family":"Konigsberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy W.","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Yi","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuining","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristyn","family":"MacPhail","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret M.","family":"Mroz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Davidson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara I.","family":"Restrepo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunita","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A.","family":"Maier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana V.","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,30]]},"reference":[{"issue":"8","key":"2919_CR1","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1513\/AnnalsATS.201511-760OC","volume":"13","author":"RP Baughman","year":"2016","unstructured":"Baughman RP, Field S, Costabel U, Crystal RG, Culver DA, Drent M, et al. 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The study was approved by the NJH Institutional Review Board (HS-3159-528).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"L.A.M. has received grant support from the Foundation for Sarcoidosis and Mallinckrodt Pharmaceuticals and serves on the advisory board for the Foundation for Sarcoidosis and the sarcoidosis advisory board for Boehringer Ingelheim. I.V.Y. has received financial support to attend the 2023 World Association for Sarcoidosis and Other Granulomatous Disorders conference and consulting fees from ElevenP15 unrelated to this work. The remaining authors do not have conflicts of interest relating to this work to disclose.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"289"}}