陳亭妏副教授研究團隊發表研究成果於 Bioinformatics

連結網址：https://academic.oup.com/bioinformatics/article/38/18/4286/6649618

Abstract

Motivation: Microbiota analyses have important implications for health and science. These analyses make use of 16S/18S rRNA gene sequencing to identify taxa and predict species diversity. However, most available tools for analyzing microbiota data require adept programming skills and in-depth statistical knowledge for proper implementation. While long-read amplicon sequencing can lead to more accurate taxa predictions and is quickly becoming more common, practitioners have no easily accessible tools with which to perform their analyses.

Results: We present MOCHI, a GUI tool for microbiota amplicon sequencing analysis. MOCHI preprocesses sequences, assigns taxonomy, identifies different abundant species and predicts species diversity and function. It takes either taxonomic count table or FASTQ of partial 16S/18S rRNA or full-length 16S rRNA gene as input. It performs analyses in real time and visualizes data in both tabular and graphical formats.

Availability and implementation: MOCHI can be installed to run locally or accessed as a web tool at https://mochi.life.nctu.edu.tw

柯泰名助理教授研究團隊發表研究成果於 Clin Transl Med.

連結網址：https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9547115/

Summary

Ankylosing spondylitis (AS) is a chronic rheumatic disease that causes disability and severe impairment in the quality of life, especially in females. However, almost nothing is known about how large heterogenous circulating immune cells are involved in developing AS. Here we used droplet-based single-cell sequencing for multi-omic profiling of PBMCs obtained from female patients and sex-matched healthy individuals and performed multimodal single-cell analyses including single-cell-level unbiased transcriptome, surface protein expression, pseudotemporal trajectory analysis, cell-cell interaction analysis, and T-cell receptor repertoire. By applying multiple filtering strategies, we selected common single-cell blood features across the patients to reveal a unique T-cell state wherein GIMAP7 was up-regulated and NFKBIA was down-regulated. Furthermore, we identified a panel of cell-surface markers and dominant T-cell clonotypes on this unique T-cell subset (NFKBIA- GIMAP7+). We identified a unique VEGI signalling pathway between the T-cells and NK cells that uncovered potential triggers for developing exclusive T-cell states in female patients with AS. This finding could be valuable for developing innovative therapies that selectively target the aberrant immune response in female patients with AS.

陳亭妏助理教授研究團隊發表研究成果於 Journal of Infection

連結網址：https://www.sciencedirect.com/science/article/pii/S0163445322005175?via%3Dihub

Summary

Objectives: RNA therapeutics is an emerging field that widens the range of treatable targets and would improve disease outcome through bypassing the antibiotic bactericidal targets to kill Mycobacterium tuberculosis (M.tb).
Methods: We screened for microRNA with immune-regulatory functions against M.tb by next generation sequencing of peripheral blood mononuclear cells, followed by validation in an independent cohort.
Results: Twenty three differentially expressed microRNAs were identified between 12 active pulmonary TB patients and 4 healthy subjects, and 35 microRNAs before and after 6-month anti-TB therapy. Enriched predicted target pathways included proteoglycan, HIF-1 signaling, longevity-regulating, central carbon metabolism, and autophagy. We validated miR-431–3p down-regulation and miR-1303 up-regulation
accompanied with corresponding changes in their predicted target genes in an independent validation cohort of 46 active TB patients, 30 latent TB infection subjects, and 24 non-infected healthy subjects. In vitro experiments of transfections with miR-431–3p mimic/miR-1303 short interfering RNA in THP-1 cells under ESAT-6 stimuli showed that miR-431–3p and miR-1303 were capable to augment and suppress autophagy/apoptosis/phagocytosis of macrophage via targeting MDR1/MMP16/RIPOR2 and ATG5, respectively.
Conclusions: This study provides a proof of concept for microRNA-based host-directed immunotherapy for active TB disease. The combined miR-431–3p over-expression and miR-1303 knock-down revealed new vulnerabilities of treatment-refractory TB disease.