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Multi-omic signatures of sarcoidosis and progression in bronchoalveolar lavage cells
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Multi-omic signatures of sarcoidosis and progression in bronchoalveolar lavage cells
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Journal Article
Multi-omic signatures of sarcoidosis and progression in bronchoalveolar lavage cells
2024
Overview
Background
Sarcoidosis is a heterogeneous granulomatous disease with no accurate biomarkers of disease progression. 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.
Methods
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.
Results
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
LYST
,
RGS14
,
SLFN12L
, and hsa-miR-199b-5p, distinguished sarcoidosis from controls. Our integrated model also demonstrated differential expression/methylation of
IL20RB
,
ABCC11
,
SFSWAP
,
AGBL4
, miR-146a-3p, and miR-378b between non-progressive and progressive sarcoidosis.
Conclusions
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.
Publisher
BioMed Central,BioMed Central Ltd,Nature Publishing Group,BMC
Subject
1-Phosphatidylinositol 3-kinase
/ Adult
/ Alveoli
/ Analysis
/ Bronchoalveolar Lavage Fluid - chemistry
/ Bronchoalveolar Lavage Fluid - cytology
/ Bronchoalveolar Lavage Fluid - immunology
/ Bronchus
/ Datasets
/ Diseases
/ DNA
/ Female
/ Genes
/ Genomes
/ Humans
/ Lavage
/ Male
/ Medicine
/ MicroRNA
/ miRNA
/ Pneumology/Respiratory System
/ RNA
/ Sarcoidosis, Pulmonary - diagnosis
/ Sarcoidosis, Pulmonary - genetics
/ Sarcoidosis, Pulmonary - metabolism
/ Sarcoidosis, Pulmonary - pathology
/ T cells
