89411bca-4c4b-4c51-b13f-49f9aa8ef399 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001006561 | EGA |
REPOSITORIES: EGA
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Project description:In this study, we explored the possibility that rare variation in the genetic background may be an additional risk factor for Parkinson's Disease (PD) in families segregating pathogenic GBA gene variants. We performed whole-genome sequencing, rare variant filtering, segregation analysis and functional validation of PD cosegregating rare genetic variation in two families segregating PD associated GBA variants c.115+1G>A (ClinVar ID: 93445, ) and p.L444P (ClinVar ID: 4288) respectively. We found rare genetic variation in the HSP70 co-chaperone DnaJ homolog subfamily B member 6 (DNAJB6) and lysosomal protein prosaposin (PSAP) as additional factors possibly influencing PD risk in the two families.
| EGAS00001004777 | EGA
Project description:Eukaryotic genes often generate a variety of RNA isoforms that can lead to functionally distinct protein variants. The synthesis and stability of RNA isoforms is however poorly characterized. The reason for this is that current methods to quantify RNA metabolism use short-read sequencing that cannot detect RNA isoforms. Here we present nanopore sequencing-based Isoform Dynamics (nano-ID), a method that detects newly synthesized RNA isoforms and monitors isoform metabolism. nano-ID combines metabolic RNA labeling, long-read nanopore sequencing of native RNA molecules and machine learning. nano-ID derived RNA stability estimates enable a distinctive evaluation of stability determining factors such as sequence, poly(A)-tail length, RNA secondary structure, translation efficiency and RNA binding proteins. Application of nano-ID to the heat shock response in human cells reveals that many RNA isoforms change their stability. nano-ID also shows that the metabolism of individual RNA isoforms differs strongly from that estimated for the combined RNA signal at a specific gene locus. nano-ID enables studies of RNA metabolism on the level of single RNA molecules and isoforms in different cell states and conditions.
2020-05-06 | GSE127890 | GEO
Project description:Chromosome segregation requires both the separation of sister chromatids and the sustained condensation of chromatids during anaphase. In yeast cells, cohesin is not only required for sister chromatid cohesion but also plays a major role in determining the structure of individual chromatids in metaphase. Separase cleavage is thought to remove all cohesin complexes from chromosomes to initiate anaphase. It is thus not clear how the length and organisation of segregating chromatids are maintained during anaphase in the absence of cohesin. Here we show that degradation of cohesin at the anaphase onset causes aberrant chromatid segregation. Hi-C analysis on segregating chromatids demonstrates that cohesin depletion causes loss of intrachromatid organisation. Surprisingly, TEV-mediated cleavage of cohesin does not dramatically disrupt chromatid organisation in anaphase, explaining why bulk segregation is achieved. In addition, we identified a small pool of cohesin complexes bound to telophase chromosomes in wildtype cells and show that they play a role in the organisation of centromeric regions. Our data demonstrate that in yeast cells, cohesin function is not over in metaphase, but extends to the anaphase period when chromatids are segregating.
2022-10-01 | GSE183481 | GEO
Project description:Synchronous beating of the heart is dependent on the efficient functioning of the cardiac intercalated disc (ID). The ID is composed of a complex protein network enabling electrical continuity and chemical communication between individual cardiomyocytes. Off late a lot of studies have shed light on increasingly prevalent cardiac diseases involving the ID. Insufficient knowledge of the ID composition makes it difficult to study these disease mechanisms in more detail. Here, for the first time using a combination of membrane enrichment, in-depth proteomics analysis and bioinformatics strategies, we have discovered a defined set of new putative ID proteins. An ID enriched membrane fraction, which included the ID markers connexin-43 (Cx43) and n-cadherin, was prepared using differential centrifugation. We quantitatively evaluated 3455 proteins for their enrichment in the ID-enriched membrane fraction with respect to their levels in the counterpart soluble fraction. An intuitive data filtering approach was used to generate a final set of 97 high potential ID proteins. These included well-known markers such as Cx43 and n-cadherin, but also several interesting novel candidates. We selected 4 candidates (Flotillin-2 (flot2), Nexilin (nexn), Popeye-domain-containg-protein 2 (popdc2) and thioredoxin-related-transmembrane-protein 2 (tmx2)) and confirmed their co-localization with n-cadherin, and thus their enrichment in the ID of human, dog and rat heart sections and isolated cardiomyocytes
2016-04-12 | PXD000947 | Pride
Project description:The expression of PD-L1 on tumor cells (TCs) is used as an immunotherapy biomarker in lung cancer, but heterogeneous intratumoral expression is often observed. Using a Digital Spatial Profiler, we performed proteomic and whole-transcriptomic analyses of TCs and immune cells (ICs) in spatially matched areas according to tumor PD-L1 expression and the status of the immune microenvironment. Several findings were validated using immunohistochemistry, The Cancer Genome Atlas, and immunotherapy cohorts. ICs in areas with high PD-L1 expression showed more features indicative of immunosuppression and exhaustion than ICs in areas with low PD-L1 expression. TCs highly expressing PD-L1 within immune-inflamed (IF) areas show up-regulation of pro-inflammatory processes, whereas TCs highly expressing PD-L1 within immune-deficient (ID) areas show up-regulation of various metabolic processes. Using differentially expressed genes of TCs between the IF and ID areas, we identified a novel prognostic gene signature for lung cancer. In addition, the high ratio of CD8+ cells to M2 macrophages was found to predict favorable outcomes in patients with PD-L1-expressing lung cancer after immune checkpoint inhibitor therapy. This study demonstrates that TCs and ICs have distinct spatial features within the tumor microenvironment that are related to tumoral PD-L1 expression and IC infiltration.
2024-08-21 | GSE265899 | GEO
Project description:Native molecule sequencing by nano-ID reveals synthesis and stability of RNA isoforms
| PRJNA525707 | ENA
Project description:Background: Parkinson’s disease (PD) is a multisystem and multifactorial disorder. Therefore, the application of modern genetic techniques may assist in unraveling its complex pathophysiology. Methods: We conducted a clinical-demographic evaluation of 126 patients with PD, all of whom were Caucasian and of Sicilian ancestry. DNA was extracted from peripheral blood for each patient, followed by sequencing using a Next-Generation Sequencing system. This system was based on a custom gene panel comprising 162 genes. The sample underwent further filtering, taking into account allele frequencies of genetic variants, their presence in the Human Gene Mutation Database, and their association in the literature with PD or other movement/neurodegenerative disorders. Results: The largest number of variants was identified in the leucine-rich repeat kinase 2 (LRRK2) gene. However, variants in other genes, such as acid beta-glucosidase (GBA), DNA polymerase gamma, catalytic subunit (POLG), and parkin RBR E3 ubiquitin protein ligase (PRKN), were also discovered. Interestingly, some of these variants had not been previously associated with PD. Conclusions: Enhancing our understanding of the genetic basis of PD and identifying new variants possibly linked to the disease will contribute to improved diagnostic accuracy, therapeutic developments, and prognostic insights for affected individuals.
2024-10-14 | E-MTAB-13523 | biostudies-arrayexpress
Project description:Immunol checkpoint blockade therapy targeting programmed-death 1 (PD-1) and its ligand PD-L1 can effectively prevent tumor immune escaping, and has been recognized with remarkable clinical benefits on cancer. Currently, antibody drugs take effect by blocking the target on the cell membrane. However, antibody drugs still face challenges in the aspect of deep penetration, multivalent recognition and chemical synthesis. Rationally designed targeting peptides is the befitting units for construction of the ‘nano antibody’. We first report herein a new peptide-AIE (aggregation-induced emission) hybrid supramolecular TPDP, which can specifically bind PD-L1 in vivo and in vitro with nanomolar affinity. It can be triggered by PD-L1 into ordered-aggregation ‘nano-spiderwebs’ and compactly cocoon the lesion surface and block PD-1/PD-L1 interaction on both membrane and cytoplasm in a dynamic manner, showing competitive effect over antibodies. It showed excellent in vivo tumor therapy effect in patient derived xenograft mice (PDX). What’s more, PD-L1 targeted antibody drugs take effect by blocking PD-L1 on the cell membrane, but intracellular PD-L1 are hard to be affect and like to be relocated on the membrane, which decreases the therapeutic benefits. In this study, the nano-spiderwebs could penetrate deeply into the cytoplasm and down-regulate the endogenous PD-L1 expression of the host, which could reduce the feedback of intracellular storage of PD-L1. We envision that this receptor-induced peptide ‘nano-spiderwebs’ will open an avenue for both blockade and inhibitor against PD-L1 and provide alternatives for targeting diagnostics and therapeutics towards this immune checkpoint.
2020-08-15 | PXD020918 |
Project description:These RNA-seq samples represent ten different tissue types for the fifth version of the maize reference genome B73, sequenced by the NAM Consortium Group. These samples correspond to project ID PRJEB32225.
2020-01-09 | E-MTAB-8628 | biostudies-arrayexpress