Project description:Unraveling the genetic basis of a collagen migration defect in patients with a combined platelet dysfunction and reduced bone density
Project description:As part of the Bloodomics collaboration we have several categories of pedigrees with diseases/syndromes relevant to cardiovascular diseases (CVD). One such pedigree, is from families who have a platelet collagen defect. Exome sequencing has been performed as part of a discovery program to ascertain potential causative variants of the clinical phenotype.
Project description:Collagen is a potent agonist for platelet activation, presenting itself as a key contributor to coagulation via interactions with platelet glycoproteins. The fine-details dictating platelet-collagen interactions are poorly understood. In particular, glycosylation could be a key determinant in the platelet-collagen interaction. Here we report an affinity purification coupled to mass spectrometry-based approach to elucidate the function of N-glycans in dictating platelet-collagen interactions. By integrative proteomic and glycoproteomic analysis of collagen-platelet interactive proteins with N-glycan manipulation, we demonstrate that the interaction of platelet adhesive receptors with collagen are highly N-glycan regulated, with glycans on many receptors playing positive roles on collagen binding, with glycans on other platelet glycoproteins exhibiting inhibitory roles on the binding to collagen. Our results significantly enhance our understanding of the details of glycans influencing the platelet-collagen interaction.
Project description:CTCF ChIP-seq of 39 primary samples derived from human acute leukemias, namely AML, T-ALL and mixed myeloid/lymphoid leukemias with CpG Island Methylator Phenotype (CIMP). Due to patient confidentiality considerations, the raw data files for this dataset have been deposited to the EGA controlled-access archive under the accession numbers EGAS00001007094 (study); EGAD00001011059 (dataset).
Project description:H3K27ac ChIP-seq of 79 primary samples derived from human acute leukemias, namely AML, T-ALL and mixed myeloid/lymphoid leukemias with CpG Island Methylator Phenotype (CIMP). In addition, 4 samples derived from CD34+ cord blood cells of healthy donors were included. Due to patient confidentiality considerations, the raw data files for this dataset have been deposited to the EGA controlled-access archive under the accession numbers EGAS00001007094 (study); EGAD00001011060 (dataset).
Project description:Platelets contain non-coding RNAs (ncRNAs), and their measurement may complement aggregometry. In the community-based Bruneck Study (N = 338), we conducted over 2,700 aggregometry measurements and over 65,000 RT-qPCR measurements in platelet releasates, platelet-poor plasma and isolated platelets. We show agonist-specific, dose-dependent platelet ncRNA release that is inhibited by aspirin. Collagen induces the strongest release for most ncRNAs, while miR-150 is hyperresponsive to ADP and miR-21 is hyperresponsive to arachidonic acid. Inflammation and high leukocyte-derived RNA content in platelets correlate inversely with platelet aggregation and platelet ncRNA release after stimulation. This inverse correlation is not observed in aspirin users. Finally, we reveal that platelet-derived microRNAs and YRNAs are carried by proteins and readily released, while circular RNAs, long non-coding RNAs and messenger RNAs are carried by vesicles and preferentially retained. Our findings provide evidence that inflammation leads to platelet pre-activation in vivo resulting in platelet exhaustion ex vivo.
Project description:We report RNA-sequencing data of 12 platelet samples isolated from four healthy individuals and incubated with either E. coli K12, E. coli O18 or no bacteria. This dataset highlights the differential effect of bacteria on spliced platelet RNA profiles.
Project description:In the past decades, the incidence of esophageal adenocarcinoma has increased dramatically in Western populations. Better understanding of disease etiology along with the identification of novel prognostic and predictive biomarkers are urgently needed to improve the dismal survival probabilities. Here, we performed comprehensive RNA (both coding and non-coding) profiling in various samples from 17 patients diagnosed with esophageal adenocarcinoma, high-grade dysplastic or non-dysplastic Barrett’s esophagus. Per patient, a blood plasma sample, and a healthy esophageal and disease tissue sample were included. In total, this comprehensive dataset consists of 102 RNA-seq libraries from 51 samples. The raw data for this study have been deposited to the controlled access archive EGA under submission EGAS00001004939.
Project description:In the past decades, the incidence of esophageal adenocarcinoma has increased dramatically in Western populations. Better understanding of disease etiology along with the identification of novel prognostic and predictive biomarkers are urgently needed to improve the dismal survival probabilities. Here, we performed comprehensive RNA (both coding and non-coding) profiling in various samples from 17 patients diagnosed with esophageal adenocarcinoma, high-grade dysplastic or non-dysplastic Barrett’s esophagus. Per patient, a blood plasma sample, and a healthy esophageal and disease tissue sample were included. In total, this comprehensive dataset consists of 102 RNA-seq libraries from 51 samples. The raw data for this study have been deposited to the controlled access archive EGA under submission EGAS00001004939.
Project description:In the past decades, the incidence of esophageal adenocarcinoma has increased dramatically in Western populations. Better understanding of disease etiology along with the identification of novel prognostic and predictive biomarkers are urgently needed to improve the dismal survival probabilities. Here, we performed comprehensive RNA (both coding and non-coding) profiling in various samples from 17 patients diagnosed with esophageal adenocarcinoma, high-grade dysplastic or non-dysplastic Barrett’s esophagus. Per patient, a blood plasma sample, and a healthy esophageal and disease tissue sample were included. In total, this comprehensive dataset consists of 102 RNA-seq libraries from 51 samples. The raw data for this study have been deposited to the controlled access archive EGA under submission EGAS00001004939.