scholarly journals Assessing Equivalent and Inverse Change in Genes Between Diverse Experiments

2021 ◽  
Author(s):  
Lisa Neums ◽  
Devin C. Koestler ◽  
Qing Xia ◽  
Jinxiang Hu ◽  
Shachi Patel ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Mononuclear Cells ◽  
Specific Treatment ◽  
Effect Sizes ◽  
Peripheral Blood Mononuclear ◽  
Bootstrap Test ◽  
Microarray Expression Data ◽  
Expression Of Genes ◽  
The Difference ◽  
Sensitivity Specificity

Abstract Background: It is important to identify when two exposures impact a molecular marker (e.g., a gene’s expression) in similar ways, for example, to learn that a new drug has a similar effect to an existing drug. Currently, statistically robust approaches for making comparisons of equivalence of effect sizes obtained from two independently run treatment versus control comparisons have not been developed. Results: Here, we propose two approaches for evaluating the question of equivalence between effect sizes of two independent studies: a bootstrap test of the Equivalent Change Index (ECI), which we previously developed, and performing Two One-Sided t-Tests (TOST) on the difference in log-fold changes directly. The ECI of a gene is computed by taking the ratio of the effect size estimates obtained from the two different studies, weighted by the maximum of the two p-values and giving it a sign indicating if the effects are in the same or opposite directions, whereas TOST is a test of whether the difference in log-fold changes lies outside a region of equivalence. We used a series of simulation studies to compare the two tests on the basis of sensitivity, specificity, balanced accuracy, and F1-socre. We found that TOST is not efficient for identifying equivalently changed gene expression values (F1-score = 0) because it is too conservative, while the ECI bootstrap test shows good performance (F1-score = 0.96). Furthermore, applying the ECI bootstrap test and TOST to publicly available microarray expression data from pancreatic cancer of tumor tissue and peripheral blood mononuclear cells (PBMC) showed that, while TOST was not able to identify any equivalently or inversely changed genes, the ECI bootstrap test identified genes associated with pancreatic cancer, intestinal cancer, and other disease types associated with pancreatic cancer. Conclusion: A bootstrap test of the ECI is a promising new statistical approach for determining if two diverse studies show similarity in the differential expression of genes and can help to identify genes which are similarly influenced by a specific treatment or exposure.

scholarly journals Discovering Non-Invasive Biomarkers Predictive of Opioid Use Disorder Treatment Response

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 173-173
Author(s):  
Amir Levine ◽  
Kelly Clemenza ◽  
Shira Weiss ◽  
Adam Bisaga ◽  
Erez Eitan ◽  
...  
Keyword(s):  
Treatment Response ◽  
Mononuclear Cells ◽  
Specific Treatment ◽  
The United States ◽  
Opioid Use Disorder ◽  
Response To Treatment ◽  
Post Translational Modification ◽  
Opioid Use ◽  
Peripheral Blood Mononuclear ◽  
Long Term Treatment

AbstractBackgroundOpioid use disorder (OUD) continues to be the driving force behind drug overdoses in the United States, killing nearly 47,000 people in 2018 alone. The increasing presence of deadlier fentanyl analogues in the heroin drug supply are putting users at a greater risk for overdose than ever before. Admissions to treatment programs for OUD have also nearly doubled since 2006, yet relapse rates remain high. In response to these alarming statistics, developing approaches to reduce overdose deaths has become an area of high priority. As it is not yet known which patients are most likely to benefit from a specific treatment, there is a dire need to utilize new molecular tools to guide precision medicine approaches and improve treatment outcomes. Here we describe a proof-of-concept study evaluating plasma-derived extracellular vesicle (EV) signatures and how they differ in patients who responded to two pharmacologically contrasting treatments for OUD: the μOR agonist methadone, and the μOR antagonist naltrexone.MethodsWe obtained blood samples from patients with OUD who remained abstinent from illicit opioids for at least 3 months during treatment with methadone (n=5) and naltrexone (n=5), as well as matched healthy controls (n=5). EVs were isolated from plasma and histones were isolated from peripheral blood mononuclear cells (PBMCs). EVs were then analyzed for lipid and histone post-translational modification (PTM) content using liquid chromatography-mass spectrometry. EV miRNA cargo was determined by RNA sequencing.ResultsWe found one lipid class and six miRNAs that differed significantly between the naltrexone group and the methadone and control groups. We also found that histone H3acK9acK14 was increasingly acetylated in PMBCs from both the methadone and naltrexone groups compared to controls.DiscussionNaltrexone, which is used in treatment of OUD and other substance use disorders as well as disorders of impulse control, was found to have multiple potential corresponding molecular signatures that can be identified after long-term treatment. It remains to be seen if these markers can also be a good predictor for treatment response. In addition, significant gender differences in EV content are found between men and women with OUD, which supports the importance of examining changes in response to treatment in a gender informed way.

R410 – Immunosuppressive Properties of Tonsil-Derived MSCs

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P180-P180
Author(s):  
Sasa Janjanin ◽  
Farida Djouad ◽  
Drago Prgomet ◽  
Rabie M Shanti ◽  
Gollapudi Kiran ◽  
...  
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Immunosuppressive Activity ◽  
Peripheral Blood Mononuclear ◽  
Murine Splenocytes ◽  
Department Of State ◽  
Wide Range ◽  
Organ Repair ◽  
The Difference

Problem We have previously shown that stroma of human palatine tonsils contains mesenchymal stem cells (MSCs) that can be isolated and expanded in culture. These tonsil-derived MSCs (T-MSCs) show multipotent differentiation properties, i.e. can differentiate along multiple mesenchymal lineages, including osteoblasts, chondrocytes, adipocytes, and myocytes. Recent findings also show that MSCs display immunoregulatory properties. Although the exact immunosuppressive mechanisms are unknown, the capacity of MSCs to suppress T-cell proliferation stimulated by allogeneic lymphocytes, dendritic cells, and phytohemaglutinin (PHA) is well documented. This study explores immunosuppressive characteristics of T-MSCs and compares them with characteristics of bone marrow-derived MSCs (BM-MSCs), a well-characterized cell population. Methods The mixed lymphocyte reaction (MLR) using human peripheral blood mononuclear cells (PBMC) from healthy donors and xenogeneic murine splenocytes was used to test the immunosuppressive properties of T-MSCs and BMMSCs. Indoleamine 2,3-dioxygenase (IDO) enzyme activity was measured spectrophotometrically based on tryptophan-to-kynurenine conversion in the supernatant. Interferon (IFN)-g in culture supernatants was quantified using a commercially available ELISA kit. Results Addition of BM-MSCs and T-MSCs both inhibited the PHA-induced proliferative response of PBMC and xenogeneic splenocytes. The difference in immunosuppressive activity correlates with the level of cell surface interferon (IFN)-g receptor as well as the differential ability of IFN-g to stimulate of IDO activity by T-MSCs compared to BM-MSCs. Conclusion T-MSCs share similar immunosuppressive characteristics as BM-MSCs in MLR. The immunosuppressive activity is significant and dose-dependent, although at a lower level than that of BM-MSCs. Significance Owing to their ease of isolation, rapid proliferation in the culture and self-renewal capacity, MSCs to date are considered an attractive candidate cell type for the development of novel cell-based therapies. They could be relevant in a wide range of clinical applications, including tissue and organ repair, drug or gene delivery to diseased tissues, improvement of allogenic hematopoietic cell transplantation, and the management of graft-versus-host disease. Support Supported by NIAMS Intramural Research Program (NIH ZO1 AR 41131). Sasa Janjanin is a recipient of the Fulbright Scholarship of the U.S. Department of State.

scholarly journals Release of Cyclooxygenase-2 and Lipoxin A4 from Blood Leukocytes in Aspirin-exacerbated Respiratory Disease

2016 ◽  
Vol 7 (3) ◽  
pp. ar.2016.7.0172
Author(s):  
Ajnacska Rozsasi ◽  
Akos Heinemann ◽  
Tilman Keck
Keyword(s):  
Respiratory Disease ◽  
Mononuclear Cells ◽  
Cyclooxygenase 2 ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Control Subjects ◽  
Aspirin Exacerbated Respiratory Disease ◽  
Blood Mononuclear Cells ◽  
Cox 2 ◽  
The Difference

Background The release of cyclooxygenase-2 (COX-2) and lipoxin A4 (LXA4) from blood mononuclear cells in patients with aspirin-exacerbated respiratory disease (AERD) is only partially understood. Objective To investigate the presence of COX-2 and LXA4 in peripheral blood mononuclear cells (PBMC) derived from patients with AERD and with nasal polyps (NP) (designated as the AERD-NP group), patients with NP without AERD (the NP group), and healthy controls without sinus disease (the control group). Methods Blood was taken from 14 patients in the AERD-NP group, 6 patients in the NP group, and 8 healthy subjects in the control group. After culturing of human PBMC, the presence of COX-2 protein and LXA4 (ELISA) was detected in the supernatant, and the results were compared among the groups. Results COX-2 and LXA4 were detectable after culturing of PBMC in all patients in the AERD-NP and NP groups and in the control subjects. COX-2 was highest in the patients in the AERD-NP group, but the difference was not significant compared with patients with non-AERD polyp and with the control subjects. LXA4 was also highest in the AERD-NP group, but the difference was also not significant compared with the patients who were non-AERD polyp and the control subjects. Conclusion Neither the release of COX-2 or LXA4 was different between the patients with AERD and with NPs, the patients without AERD and with NPs, and the healthy control group. The release of these proteins in AERD needs further investigation.

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