Similar Datasets
Project description:Reproducibility in molecular and cellular studies is fundamental to scientific discovery. To establish the reproducibility of a well-defined long-term neuronal differentiation protocol, we repeated the cellular and molecular comparison of the same two iPSC lines across five distinct laboratories. Despite uncovering acceptable variability within individual laboratories, we detect poor cross-site reproducibility of the differential gene expression signature between these two lines. Factor analysis identifies the laboratory as the largest source of variation along with several variation-inflating confounders such as passaging effects and progenitor storage. Single-cell transcriptomics shows substantial cellular heterogeneity underlying inter-laboratory variability and being responsible for biases in differential gene expression inference. Factor analysis-based normalization of the combined dataset can remove the nuisance technical effects, enabling the execution of robust hypothesis-generating studies. Our study shows that multi-center collaborations can expose systematic biases and identify critical factors to be standardized when publishing novel protocols, contributing to increased cross-site reproducibility.
| S-EPMC6178242 | biostudies-literature
Project description:Reproducibility in molecular and cellular studies is fundamental to scientific discovery. To establish the reproducibility of a well-defined long term neuronal differentiation protocol, we repeated the cellular and molecular comparison of the same two iPSC lines across five distinct laboratories. Despite uncovering acceptable variability within individual laboratories, we detect poor cross-site reproducibility of the differential gene expression signature between these two lines. Factor analysis identifies the laboratory as the largest source of variation along with several variation-inflating confounds such as passaging effects and progenitor storage. Single cell transcriptomics shows substantial cellular heterogeneity underlying inter-laboratory variability and being responsible for biases in differential gene expression inference. Factor analysis-based normalization of the combined dataset can remove the nuisance technical effects, enabling the execution of robust hypothesis generating studies. Our study shows that multi-center collaborations can expose systematic biases and identify critical factors to be standardized when publishing novel protocols, contributing to increased cross-site reproducibility.
2018-08-20 | GSE118733 | GEO
Project description:Reproducibility in molecular and cellular studies is fundamental to scientific discovery. To establish the reproducibility of a well-defined long term neuronal differentiation protocol, we repeated the cellular and molecular comparison of the same two iPSC lines across five distinct laboratories. Despite uncovering acceptable variability within individual laboratories, we detect poor cross-site reproducibility of the differential gene expression signature between these two lines. Factor analysis identifies the laboratory as the largest source of variation along with several variation-inflating confounds such as passaging effects and progenitor storage. Single cell transcriptomics shows substantial cellular heterogeneity underlying inter-laboratory variability and being responsible for biases in differential gene expression inference. Factor analysis-based normalization of the combined dataset can remove the nuisance technical effects, enabling the execution of robust hypothesis generating studies. Our study shows that multi-center collaborations can expose systematic biases and identify critical factors to be standardized when publishing novel protocols, contributing to increased cross-site reproducibility.
2018-08-20 | GSE118734 | GEO
Project description:Reproducibility of molecular phenotypes after long-term differentiation to Human iPSC-Derived Neurons: a multi-site omics study
| PRJNA486653 | ENA
Project description:Reproducibility of molecular phenotypes after long-term differentiation to Human iPSC-Derived Neurons: a multi-site omics study [bulk]
| PRJNA486654 | ENA
Project description:Reproducibility of molecular phenotypes after long-term differentiation to Human iPSC-Derived Neurons: a multi-site omics study [single-cell]
| PRJNA486655 | ENA
Project description:The genetic architecture of non-small cell lung cancer (NSCLC) is relevant to smoking status. However, the genetic contribution of long-term smoking cessation to the prognosis of NSCLC patients remains largely unknown. We conducted a genome-wide association study primarily on the prognosis of 1299 NSCLC patients of long-term former smokers from independent discovery (n = 566) and validation (n = 733) sets, and used in-silico function prediction and multi-omics analysis to identify single nucleotide polymorphisms (SNPs) on prognostics with NSCLC. We further detected SNPs with at least moderate association strength on survival within each group of never, short-term former, long-term former, and current smokers, and compared their genetic similarity at the SNP, gene, expression quantitative trait loci (eQTL), enhancer, and pathway levels. We identified two SNPs, rs34211819TNS3 at 7p12.3 (P = 3.90 × 10-9) and rs1143149SEPT7 at 7p14.2 (P = 9.75 × 10-9), were significantly associated with survival of NSCLC patients who were long-term former smokers. Both SNPs had significant interaction effects with years of smoking cessation (rs34211819TNS3: Pinteraction = 8.0 × 10-4; rs1143149SEPT7: Pinteraction = 0.003). In addition, in silico function prediction and multi-omics analysis provided evidence that these QTLs were associated with survival. Moreover, comparison analysis found higher genetic similarity between long-term former smokers and never-smokers, compared to short-term former smokers or current smokers. Pathway enrichment analysis indicated a unique pattern among long-term former smokers that was related to immune pathways. This study provides important insights into the genetic architecture associated with long-term former smoking NSCLC.
| S-EPMC8128887 | biostudies-literature
Project description:The authors aimed to assess the reproducibility of normotension and white-coat, masked, and sustained hypertension in 839 untreated patients who underwent two separate assessments (median, 3; interquartile range, 0-13 months) by both office and ambulatory blood pressure (BP) monitoring (ABPM). The proportion of patients falling into the same category in the two assessments was: 52% normotension and 55% white-coat, 47% masked, and 82% sustained hypertension. The most frequent switch was to sustained hypertension (26% of white-coat and 33% of masked hypertension). No clinical factors predicted the change in category, except for higher office diastolic BP in patients with masked hypertension who developed sustained hypertension, compared with those who remained with masked hypertension (84±4 mm Hg vs 80±5 mm Hg; P=.006). The reproducibility of hypertension phenotypes was highly dependent on the time between assessments. The authors conclude that white-coat and masked hypertension phenotypes are only reproducible in the short-term, while they frequently shift towards sustained hypertension in the long-term.
| S-EPMC8032105 | biostudies-literature
Project description:The granulin (GRN) gene stands out as a prominent player in frontotemporal degeneration (FTD). Progranulin (PGRN) is a protein encoded by the GRN gene. Mutations in the GRN gene leading to PGRN deficiency are associated with lysosomal storage diseases and various neurodegenerative diseases. Despite the significance of GRN function, the specific impact of GRN-/- condition on diverse biomolecules such as proteins, lipids, and metabolites remain unclear. This study employs a multi-omics approach, integrating proteomics, lipidomics, and metabolomics analyses for comprehensively unraveling the molecular alterations by GRN-/- condition. Proteins, lipids, and metabolites were obtained from the same sample using a single extraction method. Our result reveals distinct molecular profiles between iPSC and neurons, emphasizing upregulated synaptic proteins such as SYN1, SYT1, VAMP2, and SV2A in proteomics, decreased cardiolipin (CL) containing 16:0 and 18:1 acyl chain in lipidomics, and shifts in acetylcholine and amino acid in metabolomics. Furthermore, the GRN-/- condition induces significant alterations across the proteome, lipidome, and metabolome of induced pluripotent stem cells (iPSC) and iPSC-derived neurons, unveiling unique metabolic pathways. Although this study was conducted at a whole cell level, this comprehensive perspective contributes to our understanding of the intricate interplay among proteins, lipids, and metabolites in neurodevelopment and neurodegenerative diseases.
2023-11-13 | MSV000093388 | MassIVE
Project description:Cell therapy products (CTP) derived from pluripotent stem cells (iPSCs) may constitute a renewable, specifically differentiated source of cells to potentially cure patients with neurodegenerative disorders. However, the immunogenicity of CTP remains a major issue for therapeutic approaches based on transplantation of non-autologous stem cell-derived neural grafts. Despite its considerable side-effects, long-term immunosuppression, appears indispensable to mitigate neuro-inflammation and prevent rejection of allogeneic CTP. Matching iPSC donors' and patients' HLA haplotypes has been proposed as a way to access CTP with enhanced immunological compatibility, ultimately reducing the need for immunosuppression. In the present work, we challenge this paradigm by grafting autologous, MHC-matched and mis-matched neuronal grafts in a primate model of Huntington's disease. Unlike previous reports in unlesioned hosts, we show that in the absence of immunosuppression MHC matching alone is insufficient to grant long-term survival of neuronal grafts in the lesioned brain.
| S-EPMC6761126 | biostudies-literature