Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gender-specific transcriptional profiles identified in β-thalassemia patients

ABSTRACT: Lifelong treatment and major complications characterize β-thalassemia patients, whether they suffer from the milder type of the disease (β-thalassemia intermedia, TI) or the severe type (β-thalassemia major, TM). This study aimed to ascertain the differences in the transcriptional profiles of TI and TM patients to identify targets for stratification and the development of personalized therapeutic strategies. RNA-seq of 49 participants (16 TI, 16 TM, 17 healthy) identified a higher number of differentially expressed genes in TM than in TI patients when compared to healthy participants portraying accurately the clinical observations. When TI patients were compared to TM, the absence of significantly differentially expressed genes highlighted the increased variability seen in the TI expression profiles suggesting that a continuous spectrum describes the disease and not distinct conditions. Although no confounding effect was seen due to different centers, age groups and various clinical characteristics, when male and female patients were compared to healthy participants of the same gender, it was evident that males and females are affected in distinctive ways by β-thalassemia. TI triggers a pronounced and consistent transcriptional signature in males, whereas a small effect is seen in females reflecting increased biological variability. TM induces transcriptional changes of similar magnitude in both genders with limited overlap between them emphasizing that different pathways are affected. Our study provides a framework for further stratification studies in β-thalassemia and highlights the need to consider gender as an important variable for developing differential diagnostic and therapeutic strategies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE117221 | GEO | 2020/08/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Plasma proteome profiling combined with clinical and genetic features reveals pathophysiological characteristics of β-thalassemia

Project description:The phenotype of β-thalassemia underlies multigene interactions, making clinical stratification complicated. An increasing number of genetic modifiers affecting the disease severity have been identified, but are still unable to meet the demand of precision diagnosis. Here, we systematically conducted a comparative plasma proteomic profiling on β-thalassemia patients and healthy controls. Plasma samples from 20 TM patients, 20 TI patients, and 20 healthy controls were used for the quantitative proteomic analysis. Among 246 dysregulated proteins, 13 core protein signatures with excellent biomarker potential are proposed. The combination of proteome and patients' clinical data revealed patients with codons 41/42 -TTCT mutations have an elevated risk of higher iron burden, dysplasia, and osteoporosis than patients with other genotypes. Notably, 85 proteins correlating to fetal hemoglobin (Hb F) were identified, among which the abundance of 27 proteins may affect the transfusion burden in β-thalassemia patients. The current study thus provides protein signatures as potential diagnostic biomarkers or therapeutic clues for β-thalassemia.

2022-03-10 | PXD032179 | iProX

β-thalassemia plasma EVs proteomics

Project description:Here, we performed plasma extracellular vesicles (EVs) proteomics on 20 β-thalassemia major (TM) patients, 20 intermedia (TI) patients, and 20 healthy controls to explore the subgroup characteristics and the potential biomarkers. The proteome of paired plasma was analyzed in parallel to compare the biomarker potential of both specimens. We first described the pathophysiological characteristics of different subtypes. More significant immunity abnormalities and lipid metabolism was separately observed in patients with TI and TM, which was consistent with the results of paired plasma proteomics. A diagnostic model consisting of six proteins with subtyping potential was proposed. Of note, superior performance of plasma EVs on patient subgroup differentiating was shown than plasma, demonstrating the potential of secreted EVs for diagnosis of β-thalassemia patients.

2022-06-15 | PXD034548 | iProX

Gender-specific transcriptional profiles identified in β-thalassemia patients

Project description:Gender-specific transcriptional profiles identified in β-thalassemia patients

| PRJNA481499 | ENA

The evolution of β-thalassemia major from minor is associated with paternal uniparental isodisomy of chromosome 11p15

Project description:β-thalassemia major can be caused by homozygous mutations of the HBB gene, most of the cases are inherited from parents who both have β-thalassemia minor. Herein, we show that a mosaic paternal uniparental isodisomy of chromosome 11p14.3-15.5 is associated with β-thalassemia major in a patient with β-thalassemia minor-that evolved to β-thalassemia major. From this case, we suggest that analysis of HBB gene for non-hematopoietic tissues should be performed in late-onset β-thalassemia major patients. Keywords: genomic

2007-05-22 | GSE7847 | GEO

circRNAs expression profiling analysis of peripheral blood from patients with β-thalassemia intermedia and major

Project description:To explore the role of circRNAs in the regulation of β-thalassemia and provide new evidence and targets for the treatment of β-thalassemia, circRNAs expression profiling was analyzed from patients with β-thalassemia intermedia and major.

2023-08-20 | GSE241141 | GEO

miRNA sequencing analysis of miRNAs expression in peripheral blood from pediatric patients with β-thalassemia

Project description:To explore the relationship between miRNAs expression and pediatric patients with β-thalassemia, we analyzed abnormal expressed miRNAs in peripheral blood of pediatric β-thalassemia by miRNA sequencing.

2023-08-28 | GSE241765 | GEO

Protemic characterisation of the β-thalassemia erythroid cells from immortalised cell lines

Project description:β-thalassemia cell lines were generated via CRISPR-Cas9 genome editing of Bristol Erythroid Line Adult (BEL-A) and differentiated to the basophilic and polychromatic erythroid cell stage. TMT comparative proteomics was then performed on stage matched WT and β-thalassemia cells isolated by FACS.

2023-10-24 | PXD044730 | Pride

Therapeutic globin expression in thalassemia patient induced pluripotent stem cells from genomic safe harbors

Project description:The advent of human induced pluripotent stem (iPS) cells enables for the first time the derivation of unlimited numbers of patient-specific stem cells and holds great promise for regenerative medicine. However, realizing the full potential of iPS cells requires robust, precise and safe strategies for their genetic modification. Safe human iPS cell engineering is especially needed for therapeutic applications, as stem cell-based therapies that rely on randomly integrated transgenes pose oncogenic risks. Here we describe a strategy to genetically modify iPS cells from patients with beta-thalassemia in a potentially clinically relevant manner. Our approach is based on the identification and selection of âsafe harborâ sites for transgene expression in the human genome. We show that thalassemia patient iPS cell clones harboring a transgene can be isolated and screened according to chromosomal position. We next demonstrate that iPS cell clones that meet our âsafe harborâ criteria resist silencing and allow for therapeutic levels of beta-globin expression upon erythroid differentiation without perturbation of neighboring gene expression. Combined bioinformatics and functional analyses thus provide a robust and dependable approach for achieving desirable levels of transgene expression from selected chromosomal loci. This approach may be broadly applicable to introducing therapeutic or suicide genes into patient specific iPS cells for use in cell therapy. iPS cell clones were derived from beta-thalassemia patients. A single copy of beta-globin transgene cis-linked to locus control region (LCR) elements and an excisable Neo-eGFP transcription unit were inserted into these cell clones. beta-globin expression was induced by erythroid differentiation.

2010-10-26 | E-GEOD-24901 | biostudies-arrayexpress

Development of pathophysiologically relevant models of sickle cell disease and β-thalassemia for therapeutic studies

Project description:β-hemoglobin disorders, such as sickle cell disease (SCD) and β-thalassemia (BT), are the most common inherited monogenic blood disorders globally. Despite decades of research, there are only four FDA-approved medications available for the management of SCD with hydroxyurea (HU) being the most widely used drug that partially benefits patients by inducing fetal hemoglobin (HbF) production. On the other hand, there are no approved oral drugs currently available for β-thalassemia patients. To our knowledge, there are currently no well-characterized erythroid progenitor cell lines available that can accurately replicate the pathophysiology of SCD and BT while also having the same genetic background apart from the disease mutation enabling consistency and reproducibility. Our novel, physiologically relevant cellular systems provide a plethora of avenues for researchers to investigate various applications related to parasite invasion, drug validation, and genome-editing in the context of SCD and BT.

2024-02-07 | PXD044642 | Pride

Genotyping of human thalassemia patients reveals that the evolution of human beta-thalassemia major from minor is associated with paternal uniparental isodisomy of chromosome 11p15

Project description:Î²-thalassemia major can be caused by homozygous mutations of the HBB gene, most of the cases are inherited from parents who both have Î²-thalassemia minor. Herein, we show that a mosaic paternal uniparental isodisomy of chromosome 11p14.3-15.5 is associated with Î²-thalassemia major in a patient with Î²-thalassemia minor-that evolved to Î²-thalassemia major. From this case, we suggest that analysis of HBB gene for non-hematopoietic tissues should be performed in late-onset Î²-thalassemia major patients. Experiment Overall Design: This study is to evaluate the cause of delay-onset Î²-thalassemia major in our patient. Patients peripheral blood, hair follicle, and oral mucosa, and her parents pripheral blood samples were analyzed.

2008-06-15 | E-GEOD-7847 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data