Differential deep RNA sequencing for diagnostic detection of microbial infections in inflammatory cardiomyopathy Journal Article
| Authors: | Huang, W.; Yin, C.; Lento, P. A.; Adem, P. V.; Dimitrova, N.; Fallon, J. T. |
| Article Title: | Differential deep RNA sequencing for diagnostic detection of microbial infections in inflammatory cardiomyopathy |
| Abstract: | BACKGROUND: Inflammatory heart disease can be triggered by a variety of causes, both infectious and noninfectious in nature. We hypothesized that inflammatory cardiomyopathy is potentially related to microbial infection. METHODS: In this retrospective study, we used deep RNA sequencing on formalin-fixed paraffin-embedded heart tissue specimens to detect pathogenic agents. We first investigated 4 single-sample cases to test the feasibility of this diagnostic protocol and further 3 control-sample paired cases to improve the protocol with differential metatranscriptomics next-generation sequencing (mtNGS) analysis. RESULTS: We demonstrate that differential mtNGS allows identification of various microbials as potentially pathogenic, for example, Cutibacterium acnes, Corynebacterium aurimucosum, and Pseudomonas denitrificans, which are usually commensal in healthy individuals. Differential mtNGS also allows characterization of human host response in each individual by profiling alterations of gene expression, networked pathways, and inferred immune cell compositions, information of which is beneficial for us to understand different etiologies and immunity roles in each case. Additionally, differential mtNGS allows the identification of genetic variants in patients that may contribute to their susceptibility to particular microbial infections. CONCLUSIONS: The demonstrated power of differential mtNGS in simultaneous capture of both the infectious microbial(s) and the status of human host immune response could help us better understand the pathogenesis of complex inflammatory cardiomyopathy, if conducted on a larger scale of the population. The developed differential mtNGS method could also shed light on its translation and adoption of such a laboratory test in clinic practice, allowing for a more effective diagnosis to guide therapeutic treatment of the disease. © 2024 American Heart Association, Inc. |
| Keywords: | adolescent; adult; clinical article; human tissue; aged; middle aged; retrospective studies; unclassified drug; genetics; case report; cd8 antigen; gene expression; inflammation; genetic variability; retrospective study; t lymphocyte receptor; immune response; genetic susceptibility; diagnosis; escherichia coli; bacterium detection; interleukin 17; cd4 antigen; methicillin resistance; methicillin resistant staphylococcus aureus; ribosome rna; sequence analysis, rna; cardiomyopathies; microbiology; rna 16s; bacterial infection; sarcoidosis; transcriptome; immunocompetent cell; formaldehyde; cardiomyopathy; paraffin; bacillus cereus; methicillin resistant staphylococcus aureus infection; enterococcus faecium; heart diseases; programmed death 1 ligand 1; paraffin embedding; cytokine receptor; commensal; pseudomonas; carditis; myocarditis; toxoplasma gondii; enterobacteriaceae; endocarditis; high throughput sequencing; high-throughput nucleotide sequencing; interleukin 25; humans; human; male; female; article; rna sequencing; propionibacterium acnes; differential gene expression; interleukin 17 receptor; rna 23s; lyme disease; infectious agent; metatranscriptomics; heart tissue; tropheryma whipplei; methicillin susceptible staphylococcus aureus infection; interleukin 17b; anaerococcus prevotii; corynebacterium aurimucosum; finegoldia magna; pseudomonas denitrificans; staphylococcus warneri; streptococcus salivarius; whipple's disease |
| Journal Title: | Circulation: Genomic and Precision Medicine |
| Volume: | 17 |
| Issue: | 4 |
| ISSN: | 2574-8300 |
| Publisher: | American Heart Association |
| Date Published: | 2024-08-01 |
| Start Page: | e004487 |
| Language: | English |
| DOI: | 10.1161/circgen.123.004487 |
| PUBMED: | 38910558 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
