Accelerating Medicines Partnership-Rheumatoid Arthritis (AMP-RA)
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ABSTRACT:
PROVIDER: PRJNA407593 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Accelerating Medicines Partnership-Systemic Lupus Erythematosus (AMP-SLE)
| PRJNA407645 | ENA
Project description:Accelerating Medicines Partnership-Rheumatoid Arthritis (AMP-RA)
| PRJNA407594 | ENA
Project description:<p>This project is analyzing tissue and blood samples from people with RA and lupus to pinpoint genes, proteins, chemical pathways, and networks involved at a single cell level. This type of modular, molecular analysis will allow comparisons across the diseases and will provide insights into key aspects of the disease process. The project will identify differences between those RA patients who respond to therapies and those who do not, as well as provide a better systems level understanding of disease mechanisms in both RA and lupus. This knowledge is essential for the development of targeted therapies and for the application of existing and future therapies to appropriate patient populations.</p> <p>Additional datasets can be accessed through ImmPort (<a href="http://www.immport.org/immport-open/public/home/studySearch">http://www.immport.org/immport-open/public/home/studySearch</a>), accession: SDY998, SDY999.</p>
| phs001457 | dbGaP
Project description:Accelerating Medicines Partnership-Systemic Lupus Erythematosus (AMP-SLE)
| PRJNA407646 | ENA
Project description:BackgroundWhole-genome sequencing data are available from several large studies across a variety of diseases and traits. However, massive storage and computation resources are required to use these data, and to achieve sufficient power for discoveries, harmonization of multiple cohorts is critical.ObjectivesThe Accelerating Medicines Partnership Parkinson's Disease program has developed a research platform for Parkinson's disease (PD) that integrates the storage and analysis of whole-genome sequencing data, RNA expression data, and clinical data, harmonized across multiple cohort studies.MethodsThe version 1 release contains whole-genome sequencing data derived from 3941 participants from 4 cohorts. Samples underwent joint genotyping by the TOPMed Freeze 9 Variant Calling Pipeline. We performed descriptive analyses of these whole-genome sequencing data using the Accelerating Medicines Partnership Parkinson's Disease platform.ResultsThe clinical diagnosis of participants in version 1 release includes 2005 idiopathic PD patients, 963 healthy controls, 64 prodromal subjects, 62 clinically diagnosed PD subjects without evidence of dopamine deficit, and 705 participants of genetically enriched cohorts carrying PD risk-associated GBA variants or LRRK2 variants, of whom 304 were affected. We did not observe significant enrichment of pathogenic variants in the idiopathic PD group, but the polygenic risk score was higher in PD both in nongenetically enriched cohorts and genetically enriched cohorts. The population analysis showed a correlation between genetically enriched cohorts and Ashkenazi Jewish ancestry.ConclusionsWe describe the genetic component of the Accelerating Medicines Partnership Parkinson's Disease platform, a solution to democratize data access and analysis for the PD research community. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article is a U.S. Government work and is in the public domain in the USA.
| S-EPMC8453903 | biostudies-literature
Project description:Retinoid homeostasis is critical for normal embryonic development, and both the deficiency and excess of these compounds are associated with congenital malformations. Here we found that SIRT1, the most conserved mammalian NAD+-dependent deacetylase, contributes to the maintenance of homeostatic retinoic acid (RA) signaling and modulates mouse embryonic stem cell (mESC) differentiation. Our data show that SIRT1 deficiency enhances RA signaling, thereby accelerating mES cell differentiation in response to RA. Our findings highlight the importance of SIRT1 in transcriptional regulation of ESC pluripotency and embryogenesis.
2014-08-21 | GSE59140 | GEO
Project description:Pathogenic missense variants in the leucine-rich repeat kinase 2 (LRRK2) gene have been identified through linkage analysis in familial Parkinson disease (PD). Subsequently, other missense variants with lower effect sizes on PD risk have emerged, as well as non-coding polymorphisms (e.g. rs76904798) enriched in PD cases in genome-wide association studies. Here we leverage recent whole-genome sequences from the Accelerating Medicines Partnership-Parkinson's Disease (AMP-PD) and the Genome Aggregation (gnomAD) databases to characterize novel missense variants in LRRK2 and explore their relationships with known pathogenic and PD-linked missense variants. Using a computational prediction tool that successfully classifies known pathogenic LRRK2 missense variants, we describe an online web-based resource that catalogs characteristics of over 1200 LRRK2 missense variants of unknown significance. Novel high-pathogenicity scoring variants, some identified exclusively in PD cases, tightly cluster within the ROC-COR-Kinase domains. Structure-function predictions support that some of these variants exert gain-of-function effects with respect to LRRK2 kinase activity. In AMP-PD participants, all p.R1441G carriers (N = 89) are also carriers of the more common PD-linked variant p.M1646T. In addition, nearly all carriers of the PD-linked p.N2081D missense variant are also carriers of the LRRK2 PD-risk variant rs76904798. These results provide a compendium of LRRK2 missense variants and how they associate with one another. While the pathogenic p.G2019S variant is by far the most frequent high-pathogenicity scoring variant, our results suggest that ultra-rare missense variants may have an important cumulative impact in increasing the number of individuals with LRRK2-linked PD.
| S-EPMC8101351 | biostudies-literature
Project description:Retinoid homeostasis is critical for normal embryonic development, and both the deficiency and excess of these compounds are associated with congenital malformations. Here we found that SIRT1, the most conserved mammalian NAD+-dependent deacetylase, contributes to the maintenance of homeostatic retinoic acid (RA) signaling and modulates mouse embryonic stem cell (mESC) differentiation. Our data show that SIRT1 deficiency enhances RA signaling, thereby accelerating mES cell differentiation in response to RA. Our findings highlight the importance of SIRT1 in transcriptional regulation of ESC pluripotency and embryogenesis. Three pairs of sh-Control and sh-SIRT1 E14 mESC cells (with dulpicate for each sample) were treated with vehicle ethanol or with 20 nM of RA for 2 days. Total RNA was isolated using a Qiagen RNA easy mini kit with on-column DNAseI treatment. RNA quality was validated with the Agilent 2100 Bioanalyzer in the microarray facility. Three-pairs of ethanol treated samples, and 4 RA treated sh-Control, and 6 RA treated sh-SIRT1 samples were analyzed by Agilent Whole Mouse Genome 4x44 formate oligo arrays (014868) (Agilent Technologies) following the Agilent 1-color microarray-based gene expression analysis protocol.
2014-08-21 | E-GEOD-59140 | biostudies-arrayexpress
Project description:Rhodothermaceae bacterium RA strain:RA Genome sequencing
| PRJNA308615 | ENA
Project description:Retinoic acid (RA), the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Due to these properties, RA has proven anti-cancer capacity. Several breast cancer cells respond to the antiproliferative effects of RA, while others are RA-resistant. However, the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here, in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes, we compared two human breast cancer cell lines, a RA-responsive one, the MCF7 cell line, and a RA-resistant one, the BT474 cell line, which depicts several alterations of the "kinome".
2016-07-05 | PXD004357 | Pride