Whole blood transcriptional profiling by RNA sequencing in healthy donors
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE120312 | GEO | 2020/12/31
REPOSITORIES: GEO
Similar Datasets
Project description: Not available
| S-EPMC3713844 | biostudies-literature
Project description:This study investigated the cellular immune response in people who had recovered from SARS-CoV2 infection (COVID-19).
2022-08-21 | GSE211378 | GEO
Project description:BackgroundMicrofluidic clotting assays permit drug action studies for hemophilia therapeutics under flow. However, limited availability of patient samples and Inter-donor variability limit the application of such assays, especially with many patients on prophylaxis.ObjectiveTo develop approaches to phenocopy hemophilia using modified healthy blood in microfluidic assays.MethodsCorn trypsin inhibitor (4 µg/mL)-treated healthy blood was dosed with either anti-factor VIII (FVIII; hemophilia A model) or a recombinant factor IX (FIX) missense variant (FIX-V181T; hemophilia B model). Treated blood was perfused at 100 s-1 wall shear rate over collagen/tissue factor (TF) or collagen/factor XIa (FXIa).ResultsAnti-FVIII partially blocked fibrin production on collagen/TF, but completely blocked fibrin production on collagen/FXIa, a phenotype reversed with 1 µmol/L bispecific antibody (emicizumab), which binds FIXa and factor X. As expected, emicizumab had no significant effect on healthy blood (no anti-FVIII present) perfused over collagen/FXIa. The efficacy of emicizumab in anti-FVIII-treated healthy blood phenocopied the action of emicizumab in the blood of a patient with hemophilia A perfused over collagen/FXIa. Interestingly, a patient-derived FVIII-neutralizing antibody reduced fibrin production when added to healthy blood perfused over collagen/FXIa. For low TF surfaces, reFIX-V181T (50 µg/mL) fully blocked platelet and fibrin deposition, a phenotype fully reversed with anti-TFPI.ConclusionTwo new microfluidic hemophilia A and B models demonstrate the potency of anti-TF pathway inhibitor, emicizumab, and a patient-derived inhibitory antibody. Using collagen/FXIa-coated surfaces resulted in reliable and highly sensitive hemophilia models.
| S-EPMC6971334 | biostudies-literature
Project description:Blood platelet RNA-sequencing is increasingly used among the scientific community. Aberrant platelet transcriptome is common in cancer or cardiovascular disease, but reference data on platelet RNA content in healthy individuals are scarce and merit complex investigation. We sought to explore the dynamics of platelet transcriptome. Datasets from 204 healthy donors were used for the analysis of splice variants, particularly with regard to age, sex, blood storage time, unit of collection or library size. Genes B2M, PPBP, TMSB4X, ACTB, FTL, CLU, PF4, F13A1, GNAS, SPARC, PTMA, TAGLN2, OAZ1 and OST4 demonstrated the highest expression in the analysed cohort, remaining substantial transcription consistency. CSF3R gene was found upregulated in males (fold change 2.10, FDR q < 0.05). Cohort dichotomisation according to the median age, showed upregulated KSR1 in the older donors (fold change 2.11, FDR q < 0.05). Unsupervised hierarchical clustering revealed two clusters which were irrespective of age, sex, storage time, collecting unit or library size. However, when donors are analysed globally (as vectors), sex, storage time, library size, the unit of blood collection as well as age impose a certain degree of between- and/or within-group variability. Healthy donor platelet transcriptome retains general consistency, with very few splice variants deviating from the landscape. Although multidimensional analysis reveals statistically significant variability between and within the analysed groups, biologically, these changes are minor and irrelevant while considering disease classification. Our work provides a reference for studies working both on healthy platelets and pathological conditions affecting platelet transcriptome.
| S-EPMC8333095 | biostudies-literature
Project description:Humans exhibit sex differences in the prevalence and presentation of many psychiatric and neurodevelopmental conditions, including Alzheimer’s disease, autism spectrum disorder (ASD), and schizophrenia; however, the ‘omic’, developmental, and environmental underpinnings of these conditions remain elusive. To illuminate these mechanisms and their interactions, and to identify potential therapies, we need large, sex-specific neurobiological data sets from model organisms whose brains exhibit similar characteristics to those of humans, including comparable sex differences. Among existing models, the rhesus macaque is likely to have the greatest translatability; however, comprehensive analyses of brain sex differences in this species are necessary to demonstrate their relevance to sex-biased human conditions. We present an in-depth investigation of sex differences in the rhesus macaque brain transcriptome (RNA-seq) across 527 samples of 15 regions from 36 free-ranging adult individuals (20F/16M), representing the largest collection of bulk brain gene expression data for this species. We identified hundreds of sex-biased genes throughout the rhesus macaque brain, most of which were shared across regions, suggesting convergent regulatory mechanisms. Similar to studies of human brains, these sex-biased genes are regulated by sex hormones and transcription factors that interact with these hormones, male-biased genes are associated with multiple sex-biased human neurological conditions (e.g., ASD, schizophrenia) and energy metabolism, and female-biased genes are associated with the immune response. We also accurately predicted sex from a relatively small number of genes per region and found that, among genes reported to escape X chromosome inactivation in humans, similar genes are the most predictive of sex both across human tissues and in this dataset. Finally, we demonstrated that sex-biased genes exhibit characteristics that facilitate rapid evolution, including a tendency to be located on the sex chromosomes, more tissue-specific expression, and higher genetic variance for expression. Overall, these findings suggest that the rhesus macaque may be an appropriate model for sex-biased human neurological conditions.
2024-06-18 | GSE180092 | GEO
Project description:The identification of COVID-19 patients with high-risk of severe disease is a challenge in routine care. We performed blood RNA-seq gene expression analyses in severe hospitalized patients compared to healthy donors. Supervised and unsupervised analyses revealed a high abundance of CD177, a specific neutrophil activation marker, contributing to the clustering of severe patients. Gene abundance correlated with high serum levels of CD177 in severe patients. These results highlight neutrophil activation as a hallmark of severe disease and CD177 assessment as a reliable prognostic marker for routine care.
2021-05-27 | GSE171110 | GEO
Project description:Human bocavirus is associated with respiratory disease worldwide, mainly in children. There are conflicting results, however, regarding the existence of the HBoV in blood donors. Three hundred whole blood samples from non-immunodeficient healthy blood donors were screened for the presence of HBoV by polymerase chain reaction. The HBoV genotype of positive samples was determined using direct gene sequencing. Twenty-one out of the three hundred blood samples were found to be positive for HBoV. Sequence analysis of the positive samples revealed that all the strains were related to the HBoV-1 type with a low rate of variation among the detected sequences. It was concluded that there is a considerable risk of contracting HBoV from a blood transfusion from normal healthy individuals.
| S-EPMC5831472 | biostudies-literature
Project description:Long non-coding RNAs (lncRNAs) and miRNAs have emerged as crucial regulators of gene expression and cell fate decisions. Here we present an integrated analysis of the ncRNA-landscape of purified human hematopoietic stem cells (HSCs) and their differentiated progenies, including granulocytes, monocytes, T-cells, NK-cells, B-cells, megakaryocytes and erythroid precursors. For each blood cell population, RNA from 5 healthy donors was hybridized onto three microarray platforms (Arraystar lncRNA V2.0, NCode™-miRNA/-ncRNA), yielding a coverage of more than 40,000 lncRNAs, 25,000 mRNAs and 900 miRNAs on 146 arrays. T-distributed stochastic neighbor embedding (t-SNE) on noncoding genes structured the dataset into groups of samples that matched the input populations, demonstrating their unique lncRNA expression profiles. Self-organizing maps (SOMs) revealed clusters of lncRNAs and mRNAs that were coordinately expressed in HSCs and during lineage commitment. Using a “guilt-by-association” approach we assigned putative functions to lncRNAs regulated during differentiation, which predicted LINC00173 as a novel non-coding regulator of granulopoiesis. We knocked down LINC00173 using two independent shRNA constructs, which resulted in diminished granulocytic in vitro differentiation, myeloid colony-formation and function. Next, we uncovered a strong and highly coordinated upregulation of miRNAs, small nucleolar RNAs (snoRNAs) and lncRNAs within the DLK1-DIO3 locus on chromosome 14 (hsa14) during megakaryocytic maturation. shRNA-mediated knock-down of noncoding members of the locus reduced erythroid colony-formation and megakaryocytic cell proliferation in vitro implicating the functional importance of this ncRNA locus in megakaryopoiesis.
2017-05-31 | GSE98830 | GEO
Project description:IntroductionHepatitis C virus (HCV) is the etiological agent for the majority of cases of non-A, non-B hepatitis. As a blood-borne virus, HCV is widely recognized as a major causative agent of post-transfusion non-A, non-B hepatitis. The prevalence of HCV and the distribution of HCV genotypes in Sri Lanka in comparison with the rest of Asia are not well known.Materials and methodsThe blood samples collected from healthy blood donors at the National Blood Transfusion Centre of Sri Lanka were screened to determine the prevalence and the genotypes of HCV among blood donors in Sri Lanka.ResultsHCV antibodies were found in 53 of 4980 blood donors. However, of the 53 only 8 positive results were confirmed by Reverse Transcription-PCR, which suggests frequent false-positive results or viral clearance. The PCR positive samples were genotyped by DNA sequencing of the Core/E1 regions of HCV genome, and all the HCV viruses belonged to genotype 3, of which 7 were 3a and 1 was 3b.ConclusionHCV is relatively rare among blood donors in Sri Lanka and only genotype 3 was detected in the studied group.
| S-EPMC3082710 | biostudies-literature
Project description:Comet assay has been used to estimate cancer risk by quantification of DNA damage and repair in response to mutagen challenge. Our goal was to adopt best practices for the alkaline comet assay to measure DNA repair capacity of white blood cells in whole blood of patients with squamous cell carcinoma of the head and neck (HNSCC). The results show that initial damage by 10 Gy of gamma radiation expressed as percent DNA in comet tail was higher in stimulated lymphocytes (61.1+/-11.8) compared to whole blood (43.0+/-12.1) but subsequent repair was similar with comet tail of approximately 20% at 15 min and 13% at 45 min after exposure. Exposure of whole blood embedded in agarose from 5 to 10 Gy gamma radiation was followed by an approximately 70% repair of the DNA damage within 45 min with a faster repair phase in the first 15 min. Variability of the measurement was lower within repeated measurements of the same person compared to measurement of different healthy individuals. The repair during first 15 min was slower (p=0.01) in ex-/non-smokers (41.0+/-2.1%) compared to smokers (50.3+/-2.7%). This phase of repair was also slower (p=0.02) in HNSCC patients (36.8+/-2.1%) compared to controls matched on age and smoking (46.4+/-3.0%). The results of this pilot study suggest that quantification of repair in whole blood following a gamma radiation challenge is feasible. Additional method optimization would be helpful to improve the assay for a large population screening.
| S-EPMC4289908 | biostudies-literature