Blood Transcriptional Endotypes in Women with Pelvic Inflammatory Disease
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ABSTRACT: By comparing blood mRNA responses of women with biopsy confimed Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC) induced pelvic inflammatory disease (PID) to those from women with CT and/or GC infection limited to their cervix and asymptomatic uninfected women determined via microarray, we discovered important pathogenic mechanisms in PID and response differences that provide a pathway to biomarker discovery. Women with GC and/or CT-induced PID exhibit overexpression of myeloid cell genes and suppression of protein synthesis, mitochondrial oxidative phosphorylation, and T-cell specific genes. Coinfected women exhibited the greatest activation of cell death pathways and suppression of responses essential for adaptive immunity. Blood microarrays reveal discrete pathobiological endotypes in women with PID that are driven by pathogen invasion of the upper genital tract.
Project description:This study used nasal transcriptomic profiling of the inferior turbinate in control and pediatric ARDS subjects to identify endotypes. This data set is for amplified specimens. The study identfied three pediatric ARDS endotypes.
Project description:This study used nasal transcriptomic profiling of the inferior turbinate in control and pediatric ARDS subjects to identify endotypes. This data set is for non-amplified specimens. The study identfied three pediatric ARDS endotypes.
Project description:Here, we report using RNA sequencing isolated from frozen tumor samples from genetically-engineered mouse models and canine samples, as well as a preserved mouse cell culture to determine endotypes, or subtypes with distinct pathobiological mechanisms, of embryonal rhabdomyosarcoma (ERMS) and nonrhabdomyosarcoma soft tissue sarcomas (NRSTS). With an unsupervised clustering approach of DNA and RNA sequencing from mouse models, canine samples, patient-derived xenograft models, and human samples we have found several major endotypes with a wide range of putative driver mutations. This study aims to define each of the several pathological mechanisms driving tumor maintenance in these tumors in order to identify effective targeted treatments for individual patients.
Project description:Sexually transmitted infections with Chlamydia trachomatis and/or Neisseria gonorrhoeae and rates of pelvic inflammatory disease (PID) in women continue to rise, with reinfection being common because of poor adaptive immunity. Diagnosis remains imprecise, and pathogenesis data are derived primarily from monoinfection of mice with C. trachomatis or N. gonorrhoeae By comparing blood mRNA responses of women with C. trachomatis- and/or N. gonorrhoeae-induced PID and histologic endometritis with those from women with C. trachomatis and/or N. gonorrhoeae infection limited to their cervix and asymptomatic uninfected women determined via microarray, we discovered important pathogenic mechanisms in PID and response differences that provide a pathway to biomarker discovery. Women with N. gonorrhoeae- and/or C. trachomatis-induced PID exhibit overexpression of myeloid cell genes and suppression of protein synthesis, mitochondrial oxidative phosphorylation, and T cell-specific genes. Coinfected women exhibited the greatest activation of cell death pathways and suppression of responses essential for adaptive immunity. Women solely infected with C. trachomatis expressed elevated levels of type I and type II IFN genes, and enhanced type I IFN-induced chemokines in cervical secretions were associated with ascension of C. trachomatis to the endometrium. Blood microarrays reveal discrete pathobiological endotypes in women with PID that are driven by pathogen invasion of the upper genital tract.
Project description:Identifying at first clinical presentation gene expression signatures that predict subsequent severity will allow clinicians to identify the most at risk groups of patients, and also enable appropriate antibiotic use. Accordingly, we characterized the blood immune profiles of patients with early/pre-sepsis to identify signatures reflecting disease severity, organ dysfunction, mortality, and specific endotypes/mechanisms.
Project description:This study aimed to establish molecular endotypes in osteoarthritis soft joint tissue driven by obesity in both load-bearing and non-load bearing joints. Transcriptomic analysis found the inflammatory landscape of OA synovial fibroblasts (SF) are independently impacted by obesity, joint loading, and anatomical site with significant heterogeneity between obese and normal weight patients. These findings demonstrate the significance of obesity in changing the inflammatory landscape of synovial fibroblasts in both load bearing and non-load bearing joints. The molecular endotypes identified may provide a route for the stratification of patients in clinical trials, providing a rational for the therapeutic targeting of specific SF subsets in specific patient populations with arthritic conditions.
Project description:Genital C. trachomatis (CT) infection may cause pelvic inflammatory disease (PID) that can lead to tubal factor infertility (TFI). Understanding the pathogenesis of chlamydial complications including the pathophysiological processes within the female host genital tract is of immense importance in preventing adverse pathology. In this study, we tested the hypothesis that the miRNA profile of a acute primary chlamydial infection characterized by temporary inflammation versus the profile associated with chronic genital chlamydial infections that might precipitate PID or TFI will be different. Thus, we analyzed and compared the differentially expressed miRNAs that regulate CT pathogenesis after a single genital infection and those involved in the development of PID and TFI after repeat infections. Mice (Mus musculus) were infected with Chlamydia muridarum once or twice with a month interval between infections, and then sacrificed and genital tract tissues were collected at 1, 2, 4, and 8 weeks after infection. miRNAs were differentially expressed in both first infection and the re-infection; however, the miRNA expression profile was different for both groups. Pathway analysis showed that, amongst other functions, the differentially regulated miRNA might be regulating several pathways involved in cellular and tissue development, disease conditions and toxicity. Grant number: 1SC2HD086066-03 Funding source: Eunice Kennedy Shriver National Institute of Child Health & Human Development Title: Discovering Novel Biomarkers Predictive of Tubal Infertility Caused by Chlamydia. Principal investigator: Yusuf Omosun Date: 05/01/2015-04/30/2019
Project description:Persistent symptoms after COVID-19 infection can affect almost half of COVID-19 survivors, leading to poor quality of life. Despite its prevalence, the pathophysiology of this phenomenon is poorly understood. We analyzed differences in gene expression between patients with and without post-COVID symptoms in hospital, at follow-up, and longitudinally. As part of the Banque Québécoise de la COVID-19 biobank, 24 adult patients who were hospitalized due to respiratory COVID-19 were enrolled. Whole blood was collected within the first 10 days in hospital and 4-12 weeks after discharge. K-medoids clustering was performed to further separate patients into clusters/endotypes for DE analysis and pathway enrichment. We found that high rates of post-COVID symptoms in hospitalized patients were associated with an inability to mount, and subsequently resolve by 4-12 weeks after discharge, a robust early response involving immune and hemostatic pathways, which was seen in two of three endotypes.