Genetic biomarker prediction based on gender disparity in asthma throughout machine learning DOI Creative Commons

Chen Cai,

F. Yuan,

Xiangwei Meng

et al.

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Sept. 13, 2024

Background Asthma is a chronic respiratory condition affecting populations worldwide, with prevalence ranging from 1–18% across different nations. Gender differences in asthma have attracted much attention. Purpose The aim of this study was to investigate biomarkers gender based on machine learning. Method data came the gene expression omnibus database (GSE69683, GSE76262, and GSE41863), which involved number 575 individuals, including 240 males 335 females. Theses samples were divided into male group female group, respectively. Grid search cross-validation employed adjust model parameters for support vector machine, random forest, decision tree logistic regression model. Accuracy, precision, recall, F 1 score used evaluate performance models during training process. After optimization, four learning utilized predict sex asthma. In order validate accuracy our results, we performed Wilcoxon tests genes expression. Result datasets GSE76262 GSE69683, regression, all achieve 100% accuracy, score. Our findings reveal that XIST serves as common biomarker among three samples, comprising total higher levels females compared ( p < 0.01). Conclusion genetic

Language: Английский

Exploring the Contribution of TLR7 to Sex-Based Disparities in Respiratory Syncytial Virus (RSV)-Induced Inflammation and Immunity DOI Creative Commons
Mark A. Miles,

Thomas D. Huttmann,

Stella Liong

et al.

Viruses, Journal Year: 2025, Volume and Issue: 17(3), P. 428 - 428

Published: March 16, 2025

TLR7 plays a key role in recognizing viral RNA to initiate an immune response. Sex-based differences the severity of RSV respiratory infections have been noted, and this may be related higher expression X-linked toll-like receptor 7 (TLR7) female cells. Indeed, has shown influence sex responses other viruses; however, its infection remains underexplored. We infected adult C57Bl/6 or knockout mice with compared specific lung between different sexes. Gene analysis revealed that had elevated levels type I II interferons, proinflammatory cytokines, chemokines, transcripts their lungs males. Additionally, females exhibited increased numbers macrophages antibody airways. Deletion diminished certain cytokine responses. Furthermore, ex vivo male alveolar resulted greater production cytokines than macrophages, suggesting inherent macrophage These findings provide new insights into mechanisms underlying pathophysiology suggest contributes enhanced inflammatory response females.

Language: Английский

Citations

0
Enhanced TLR7-dependent production of type I interferon by pDCs underlies pandemic chilblains DOI Creative Commons
Fanny Saidoune, Danyel Lee, Jérémy Di Domizio

et al.

The Journal of Experimental Medicine, Journal Year: 2025, Volume and Issue: 222(7)

Published: April 14, 2025

Outbreaks of chilblains were reported during the COVID-19 pandemic. Given essential role type I interferon (I-IFN) in protective immunity against SARS-CoV-2 and association with inherited interferonopathies, we hypothesized that excessive I-IFN responses to might underlie occurrence this context. We identified a transient signature chilblain lesions, accompanied by an acral infiltration activated plasmacytoid dendritic cells (pDCs). Patients otherwise asymptomatic or had mild disease without seroconversion. Their leukocytes produced abnormally high levels upon TLR7 stimulation agonists ssRNA viruses—particularly SARS-CoV-2—but not DNA TLR9 dsDNA virus HSV-1. Moreover, patients’ pDCs displayed cell-intrinsic hyperresponsiveness regardless levels. Inherited deficiency confers predisposition life-threatening COVID-19. Conversely, our findings suggest enhanced activity predisposed individuals could confer innate, pDC-mediated, sterilizing infection, I-IFN–driven as trade-off.

Language: Английский

Citations

0
Identifying genetic errors of immunity due to mosaicism DOI
Elizabeth G. Schmitz, Malachi Griffith, Obi L. Griffith

et al.

The Journal of Experimental Medicine, Journal Year: 2025, Volume and Issue: 222(5)

Published: April 15, 2025

Inborn errors of immunity are monogenic disorders the immune system that lead to deficiency and/or dysregulation in patients. Identification precise genetic causes disease aids diagnosis and advances our understanding human system; however, a significant portion patients lack molecular diagnosis. Somatic mosaicism, changes subset cells, is emerging as an important mechanism both young older Here, we review current landscape somatic methods for detection validation variants.

Language: Английский

Citations

0
UBA1-CDK16: A Sex-Specific Chimeric RNA and Its Role in Immune Sexual Dimorphism DOI Open Access
Xinrui Shi,

Loryn Facemire,

Sandeep Singh

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 15, 2024

RNA processing mechanisms, such as alternative splicing and editing, have been recognized critical means to expand the transcriptome. Chimeric RNAs formed by intergenic provide another potential layer of diversification. By analyzing a large set RNA-Seq data validating results in over 1,200 blood samples, we identified

Language: Английский

Citations

2
Female-bias in systemic lupus erythematosus: How much is the X chromosome to blame? DOI Creative Commons

Adriana Vieira,

Inês Almada-Correia,

Joana Inácio

et al.

Biology of Sex Differences, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 7, 2024

Language: Английский

Citations

2
Altered X-chromosome inactivation predisposes to autoimmunity DOI Creative Commons
Christophe Huret, Léa Férrayé,

Antoine David

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: April 21, 2023

Abstract In mammals, males and females show marked differences in immune responses. Males are globally more sensitive to infectious diseases while susceptible systemic autoimmunity. X-chromosome inactivation (XCI), the epigenetic mechanism that ensures silencing of one X females, may participate these sex-biases. Here, we perturbed expression trigger XCI, non-coding RNA Xist, female mice. This resulted reactivation genes on inactive X, including members Toll-like receptor 7 (TLR7) signalling pathway, monocyte/macrophages, dendritic B cells. Consequently, mice spontaneously developed inflammatory signs typical lupus, anti-nucleic acid autoantibodies, increased frequencies age-associated germinal centre cells expansion monocyte/macrophages Mechanistically, TLR7 is dysregulated macrophages, which leads sustained target upon stimulation. These findings provide a direct link between maintenance XCI female-biased autoimmune manifestations highlight altered as cause Teaser The reason why autoimmunity mostly affects women unclear. aberrant induces lupus

Language: Английский

Citations

4
Sex-Dependent Effects on Influenza-Specific Antibody Quantity and Neutralizing Activity following Vaccination of Newborn Non-Human Primates Is Determined by Adjuvants DOI Creative Commons
Beth C. Holbrook, Elene A. Clemens, Martha A. Alexander‐Miller

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(4), P. 415 - 415

Published: April 15, 2024

A number of studies have demonstrated the role sex in regulating immune responses to vaccination. However, these findings been limited adults for both human and animal models. As a result, our understanding impact on vaccine newborn is highly limited. Here, we probe this important question using non-human primate model. We leveraged prior analysis two cohorts newborns, with one being mother-reared nursery-reared. This provided adequate numbers males females interrogate response inactivated influenza vaccines alone or adjuvanted R848, flagellin, both. found that, contrast what has reported adults, non-adjuvanted virus induced similar levels virus-specific IgG male female newborns. inclusion either combination resulted higher antibody titers compared males. Sex-specific increases neutralizing were only observed when R848 flagellin present. These data, generated translational NHP model, provide novel insights into

Language: Английский

Citations

1
Bioinformatics analysis to identify the relationship between human papillomavirus-associated cervical cancer, toll-like receptors and exomes: A genetic epidemiology study DOI Creative Commons
Fabiana de Campos Gomes, Deizyane dos Reis Galhardo,

Aline Carvalho Gonçalves Navegante

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(8), P. e0305760 - e0305760

Published: Aug. 29, 2024

Genetic variants may influence Toll-like receptor (TLR) signaling in the immune response to human papillomavirus (HPV) infection and lead cervical cancer. In this study, we investigated pattern of TLR expression transcriptome HPV-positive HPV-negative cancer samples looked for potentially related gene alterations exomes from different populations.

Language: Английский

Citations

1
Human monocyte subtype expression of neuroinflammation- and regeneration-related genes is linked to age and sex DOI Creative Commons

Juliane F. Tampé,

Emanuela Monni,

Sara Palma-Tortosa

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(10), P. e0300946 - e0300946

Published: Oct. 30, 2024

Aging profoundly affects the immune system leading to an increased propensity for inflammation. Age-related dysregulation of cells is implicated in development and progression numerous age-related diseases such as: cardiovascular diseases, neurodegenerative disorders, metabolic syndromes. Monocytes monocyte-derived macrophages, being important players inflammatory response, significantly influence aging process associated increase disease risk. Ischemic stroke among where inflammation, particularly plays deteriorating role but could also strongly promote post-stroke recovery. Also, biological sex influences incidence, presentation, outcomes ischemic stroke, reflecting both differences between men women. Here, we studied whether human peripheral blood monocyte subtype (classical, intermediate, non-classical) expression genes stroke-related inflammation tissue regeneration depends on age sex. A flow cytometry analysis samples from 44 healthy volunteers (male female, aged 28 98) showed that contrast other cells, proportion NK-cells females. The B-cells decreased sexes with age. Gene by qPCR identified several differentially correlating within different subtypes. Interestingly, ANXA1 CD36 a consistent all monocytes, specifically intermediate ( ) non-classical Other IL-1β , S100A8 TNFα CD64 CD33 TGFβ1 TLR8 CD91 were changed subtypes increasing Most age-dependent gene changes expressed female monocytes. Our data shed light nuanced interplay shaping inflammation- regeneration-related distinct Understanding these dynamics pave way targeted interventions personalized approaches care, population individuals sexes.

Language: Английский

Citations

1
Régulation du chromosome X et spécificités fonctionnelles des cellules femelles DOI Creative Commons
Julie Chaumeil,

Céline Morey

médecine/sciences, Journal Year: 2024, Volume and Issue: 40(12), P. 935 - 946

Published: Dec. 1, 2024

Et si posséder deux chromosomes X conférait aux cellules femelles des spécificités exclusives et expliquait les différences de susceptibilité hommes femmes à certaines maladies ? Pourtant, l’un est réprimé aléatoirement dans chaque cellule femelle dès le stade embryonnaire, ce qui, théoriquement, remet sexes égalité. Cette inactivation du chromosome un processus épigénétique unique : elle agit l’échelle d’un entier aboutit mosaïcisme d’expression gènes au niveau l’organisme. Cependant certains échappent cette semble être plus labile types cellulaires. Quelles en sont conséquences physiologiques question commence explorée, notamment systèmes immunitaires nerveux qui présentent différentes biais sexe.

Citations

1