scholarly journals Comparison of subtyping approaches and the underlying drivers of microbial signatures for chronic rhinosinusitis

2018 ◽  
Author(s):  
Kristi Biswas ◽  
Raewyn Cavubati ◽  
Shan Gunaratna ◽  
Michael Hoggard ◽  
Sharon Waldvogel-Thurlow ◽  
...  
Keyword(s):  
Tight Junction ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Expression Profiles ◽  
Alpha Diversity ◽  
Careful Consideration ◽  
Future Studies ◽  
Microbial Dysbiosis ◽  
Gene And Protein Expression ◽  
Protein Expression Profiles

Chronic rhinosinusitis (CRS) is a heterogeneous condition characterised by persistent sinus inflammation and microbial dysbiosis. This study aimed to identify clinically relevant sub-groups of CRS patients based on distinct microbial signatures, with a comparison to the commonly used phenotypic subgrouping approach. The underlying drivers of these distinct microbial clusters were also investigated, together with associations with epithelial barrier integrity. Sinus biopsies were collected from CRS patients (n=23), and disease controls (n=8). Expression of 42 tight junction genes was evaluated using quantitative PCR, together with microbiota analysis and immunohistochemistry for measuring mucosal integrity and inflammation. CRS patients clustered into two distinct microbial sub-groups using probabilistic modelling Dirichlet (DC) multinomial mixtures. DC1 exhibited significantly reduced bacterial diversity, increased dispersion, and was dominated by Pseudomonas, Haemophilus, and Achromobacter. DC2 had significantly elevated B-cells, incidence of nasal polyps, and higher numbers of Anaerococcus, Megasphaera, Prevotella, Atopobium, and Propionibacterium. In addition, each DC exhibited distinct tight junction gene and protein expression profiles compared with controls. Stratifying CRS patients based on clinical phenotypic subtypes (absence or presence of nasal polyps (CRSsNP or CRSwNP respectively) or with cystic fibrosis (CRSwCF)) did account for a larger proportion of the variation in the microbial dataset compared with DC groupings. However, no significant differences between CRSsNP and CRSwNP cohorts were observed for inflammatory markers, beta-dispersion and alpha diversity measures. In conclusion, both stratification approaches used had benefits and pitfalls, but DC clustering did provide greater resolution when studying tight junction impairment. Future studies in CRS should give careful consideration into the patient subtyping approach used.

scholarly journals Comparison of Subtyping Approaches and the Underlying Drivers of Microbial Signatures for Chronic Rhinosinusitis

mSphere ◽  
2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Kristi Biswas ◽  
Raewyn Cavubati ◽  
Shan Gunaratna ◽  
Michael Hoggard ◽  
Sharon Waldvogel-Thurlow ◽  
...  
Keyword(s):  
Tight Junction ◽  
Chronic Rhinosinusitis ◽  
Inflammatory Markers ◽  
Nasal Polyps ◽  
Epithelial Barrier ◽  
Clear Understanding ◽  
Microbial Composition ◽  
Data Set ◽  
Heterogeneous Condition ◽  
Gene And Protein Expression

ABSTRACT Chronic rhinosinusitis (CRS) is a heterogeneous condition characterized by persistent sinus inflammation and microbial dysbiosis. This study aimed to identify clinically relevant subgroups of CRS patients based on distinct microbial signatures, with a comparison to the commonly used phenotypic subgrouping approach. The underlying drivers of these distinct microbial clusters were also investigated, together with associations with epithelial barrier integrity. Sinus biopsy specimens were collected from CRS patients (n = 23) and disease controls (n = 8). The expression of 42 tight junction genes was evaluated using quantitative PCR together with microbiota analysis and immunohistochemistry for measuring mucosal integrity and inflammation. CRS patients clustered into two distinct microbial subgroups using probabilistic modelling Dirichlet (DC) multinomial mixtures. DC1 exhibited significantly reduced bacterial diversity and increased dispersion and was dominated by Pseudomonas, Haemophilus, and Achromobacter. DC2 had significantly elevated B cells and incidences of nasal polyps and higher numbers of Anaerococcus, Megasphaera, Prevotella, Atopobium, and Propionibacterium. In addition, each DC exhibited distinct tight junction gene and protein expression profiles compared with those of controls. Stratifying CRS patients based on clinical phenotypic subtypes (absence or presence of nasal polyps [CRSsNP or CRSwNP, respectively] or with cystic fibrosis [CRSwCF]) accounted for a larger proportion of the variation in the microbial data set than with DC groupings. However, no significant differences between CRSsNP and CRSwNP cohorts were observed for inflammatory markers, beta-dispersion, and alpha-diversity measures. In conclusion, both approaches used for stratifying CRS patients had benefits and pitfalls, but DC clustering provided greater resolution when studying tight junction impairment. Future studies in CRS should give careful consideration to the patient subtyping approach used. IMPORTANCE Chronic rhinosinusitis (CRS) is a major human health problem that significantly reduces quality of life. While various microbes have been implicated, there is no clear understanding of the role they play in CRS pathogenesis. Another equally important observation made for CRS patients is that the epithelial barrier in the sinonasal cavity is defective. Finding a robust approach to subtype CRS patients would be the first step toward unravelling the pathogenesis of this heterogeneous condition. Previous work has explored stratification based on the clinical presentation of the disease (with or without polyps), inflammatory markers, pathology, or microbial composition. Comparisons between the different stratification approaches used in these studies have not been possible due to the different cohorts, analytical methods, or sample sites used. In this study, two approaches for subtyping CRS patients were compared, and the underlying drivers of the heterogeneity in CRS were also explored.

scholarly journals Immune Imbalance in Nasal Polyps of Caucasian Chronic Rhinosinusitis Patients Is Associated with a Downregulation of E-Selectin

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Michael Könnecke ◽  
Robert Böscke ◽  
Anja Waldmann ◽  
Karl-Ludwig Bruchhage ◽  
Robert Linke ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Essential Role ◽  
Expression Profiles ◽  
Inferior Turbinate ◽  
Significant Inhibition ◽  
Significant Difference ◽  
Mrna And Protein Expression ◽  
Immune Imbalance ◽  
Protein Expression Profiles

Chronic rhinosinusitis with nasal polyps (CRSwNP) in Caucasians is a chronic Th2 inflammatory disease of the nasal and paranasal mucosa and the recruitment of leukocytes to the site of inflammation is poorly understood. We studied mRNA and protein expression profiles of adhesion molecules in nasal polyp and associated inferior turbinate tissues using molecular, biochemical, and immunohistological methods. Analysis showed a strongly decreased E-selectin expression in nasal polyps with a significant difference between eosinophil and neutrophil counts in nasal polyps and balanced counts in inferior turbinates. E-selectin expression is known to be downregulated in a Th2 milieu and has an essential role in immunosurveillance by locally activating neutrophil arrest and migratory function. A downregulation of E-selectin may come along with an immune imbalance in Caucasian nasal polyps due to a significant inhibition of neutrophil recruitment. Therefore, we suggest that an upregulation of E-selectin and the associated influx of neutrophils may play a significant role in the resolution of inflammation as well as for the pathophysiology of nasal polyps of Caucasian chronic rhinosinusitis patients.

Gene and protein expression profiles of JAK-STAT signalling pathway in the developing brain of the Ts1Cje down syndrome mouse model

2019 ◽  
Vol 129 (9) ◽  
pp. 871-881 ◽  
Author(s):  
Han-Chung Lee ◽  
Hadri Hadi Md Yusof ◽  
Melody Pui-Yee Leong ◽  
Shahidee Zainal Abidin ◽  
Eryse Amira Seth ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Mouse Model ◽  
Protein Expression ◽  
Expression Profiles ◽  
Developing Brain ◽  
Signalling Pathway ◽  
Gene And Protein Expression ◽  
Protein Expression Profiles

Gene and Protein Expression Profiles ofShewanella oneidensisduring Anaerobic Growth with Different Electron Acceptors

2002 ◽  
Vol 6 (1) ◽  
pp. 39-60 ◽  
Author(s):  
Alex S. Beliaev ◽  
Dorothea K. Thompson ◽  
Tripti Khare ◽  
Hanjo Lim ◽  
Craig C. Brandt ◽  
...  
Keyword(s):  
Protein Expression ◽  
Expression Profiles ◽  
Electron Acceptors ◽  
Anaerobic Growth ◽  
Gene And Protein Expression ◽  
Protein Expression Profiles

scholarly journals Cellular Functions and Gene and Protein Expression Profiles in Endothelial Cells Derived from Moyamoya Disease-Specific iPS Cells

PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0163561 ◽  
Author(s):  
Shuji Hamauchi ◽  
Hideo Shichinohe ◽  
Haruto Uchino ◽  
Shigeru Yamaguchi ◽  
Naoki Nakayama ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Protein Expression ◽  
Moyamoya Disease ◽  
Expression Profiles ◽  
Ips Cells ◽  
Cellular Functions ◽  
Gene And Protein Expression ◽  
Protein Expression Profiles ◽  
Disease Specific

scholarly journals Global Molecular and Morphological Effects of 24-Hour Chromium(VI) Exposure on Shewanella oneidensis MR-1

2006 ◽  
Vol 72 (9) ◽  
pp. 6331-6344 ◽  
Author(s):  
Karuna Chourey ◽  
Melissa R. Thompson ◽  
Jennifer Morrell-Falvey ◽  
Nathan C. VerBerkmoes ◽  
Steven D. Brown ◽  
...  
Keyword(s):  
Untreated Control ◽  
Expression Profiles ◽  
Shewanella Oneidensis ◽  
Transcriptome Profiling ◽  
Molecular Response ◽  
Chromium Vi ◽  
Stress Protection ◽  
Gene And Protein Expression ◽  
Genes Encoding ◽  
Protein Expression Profiles

ABSTRACT The biological impact of 24-h (“chronic”) chromium(VI) [Cr(VI) or chromate] exposure on Shewanella oneidensis MR-1 was assessed by analyzing cellular morphology as well as genome-wide differential gene and protein expression profiles. Cells challenged aerobically with an initial chromate concentration of 0.3 mM in complex growth medium were compared to untreated control cells grown in the absence of chromate. At the 24-h time point at which cells were harvested for transcriptome and proteome analyses, no residual Cr(VI) was detected in the culture supernatant, thus suggesting the complete uptake and/or reduction of this metal by cells. In contrast to the untreated control cells, Cr(VI)-exposed cells formed apparently aseptate, nonmotile filaments that tended to aggregate. Transcriptome profiling and mass spectrometry-based proteomic characterization revealed that the principal molecular response to 24-h Cr(VI) exposure was the induction of prophage-related genes and their encoded products as well as a number of functionally undefined hypothetical genes that were located within the integrated phage regions of the MR-1 genome. In addition, genes with annotated functions in DNA metabolism, cell division, biosynthesis and degradation of the murein (peptidoglycan) sacculus, membrane response, and general environmental stress protection were upregulated, while genes encoding chemotaxis, motility, and transport/binding proteins were largely repressed under conditions of 24-h chromate treatment.

Sign in / Sign up

Export Citation Format

Share Document