Human disease causing Kinetoplastids
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA398352 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Two S. pyogenes isolates causing invasive disease in England 2019
| PRJEB36425 | ENA
Project description:Purpose: The goal of this RNA sequencing (RNA-seq) study is to identify aberrations in the astrocyte transcriptional landscape caused by R270X mutation in MECP2. Methods: mRNA-seq analysis was performed on total RNA extracted from human embryonic stem cell (ESCs)-derived wild-type (WT) and MECP2-R270X mutant astrocytes. The R270X mutation was inserted into ESCs (line H1) via CRISPR/Cas9 technology. Samples were generated in triplicates, sequenced by Illumina NovaSeq 6000 Sequencing System. Raw reads were first trimmed for 10 bases at the 5’end to remove reads with biased nucleotide (ACGT) distribution. Trimmed reads were then aligned to the Homo sapiens genome (GRCh38p12, GENCODE, primary assembly), using STAR aligner. Differential gene expression (DEG) analyses on the read counts were performed using DESeq2. Genes with sum of read counts across all samples with less 10 were filtered out from analysis. Results: Our RNA-seq analysis showed that 1,621 genes were dysregulated in mutant astrocytes (fold-change >1.5 or <2/3; padj < 0.05, average reads count >10 in at least one genotype)
2024-02-15 | GSE185726 | GEO
Project description:Identification of Disease-Causing Mutations in SCID using Exome-Wide Sequencing
| PRJNA104971 | ENA
Project description:Characterizing Disease-causing Variants Using Personal Genomes with Large Recurrent Deletions
| PRJNA763971 | ENA
Project description:Characterizing Disease-causing Variants Using Personal Genomes with Large Recurrent Deletions
| PRJNA763972 | ENA
Project description:About 45% of congenital heart disease (CHD) is caused by rare gene mutations. Non-coding mutations that perturb cis-regulatory elements (CREs) likely contribute to CHD among the remaining cases without clear etiology. However, identifying CHD-causing non-coding variants has been problematic. We combined human induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) differentiation and a lentivirus-mediated massively parallel reporter assay (lentiMPRA) to create a high-throughput platform to measure human cardiac enhancer activity. We tested 2451 candidate human cardiac enhancers, identified 1185 with measurable activity, and functionally dissected 123 of these by systematic tiling mutagenesis. We functionally evaluated 6761 non-coding de novo variants (ncDNVs) prioritized from the whole genome sequencing (WGS) of 749 CHD trios. 397 ncDNVs significantly affected cardiac CRE activity. Remarkably, 53% of these ncDNVs increased enhancer activity, often at regions with undetectable enhancer activity in the reference sequence. We introduced 10 of these DNVs associated with CHD genes into iPSCs and found that 4 altered expression of neighboring genes. Moreover, these 4 DNVs also altered cardiomyocyte differentiation, as assessed by single nucleus RNA sequencing. Using the MPRA data, we developed a regression model to prioritize future DNVs for functional testing and demonstrate that this model finds enrichment of DNVs in a second, independent WGS cohort. Taken together, we developed a scalable system to measure the impact of non-coding DNVs on CRE activity and deployed this platform to systematically assess the contribution of non-coding DNVs to CHD.
2022-08-05 | GSE210376 | GEO
Project description:Whole genome sequencing (WGS) of tongue cancer samples and cell line was performed to identify the fusion gene translocation breakpoint. WGS raw data was aligned to human reference genome (GRCh38.p12) using BWA-MEM (v0.7.17). The BAM files generated were further analysed using SvABA (v1.1.3) tool to identify translocation breakpoints. The translocation breakpoints were annotated using custom scripts, using the reference GENCODE GTF (v30). The fusion breakpoints identified in the SvABA analysis were additionally confirmed using MANTA tool (v1.6.0).
2024-02-17 | E-MTAB-12534 | biostudies-arrayexpress
Project description:Non-alcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), is a progressive metabolic disorder that begins with aberrant triglyceride accumulation in the liver and can lead to cirrhosis and cancer. A common variant in the gene PNPLA3, encoding the protein PNPLA3-I148M, is the strongest known genetic risk factor for MASLD. Despite its discovery twenty years ago, the function of PNPLA3, and now the role of PNPLA3-I148M, remain unclear. In this study, we sought to dissect the biogenesis of PNPLA3 and PNPLA3-I148M and characterize changes induced by endogenous expression of the disease-causing variant. Contrary to bioinformatic predictions and prior studies with overexpressed proteins, we demonstrate here that PNPLA3 and PNPLA3-I148M are not endoplasmic reticulum-resident transmembrane proteins. To identify their intracellular associations, we generated a paired set of isogenic human hepatoma cells expressing PNPLA3 and PNPLA3-I148M at endogenous levels. Both proteins were enriched in lipid droplet, Golgi, and endosomal fractions. Purified PNPLA3 and PNPLA3-I148M proteins associated with phosphoinositides commonly found in these compartments. Despite a similar fractionation pattern as the wild-type variant, PNPLA3-I148M induced morphological changes in the Golgi apparatus, including increased lipid droplet-Golgi contact sites, which were also observed in I148M-expressing primary human patient hepatocytes. In addition to lipid droplet accumulation, PNPLA3-I148M expression caused significant proteomic and transcriptomic changes that resembled all stages of liver disease. Cumulatively, we validate an endogenous human cellular system for investigating PNPLA3-I148M biology and identify the Golgi apparatus as a central hub of PNPLA3-I148M-drivencellular change.
2024-04-09 | GSE261297 | GEO
Project description:Non-alcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), is a progressive metabolic disorder that begins with aberrant triglyceride accumulation in the liver and can lead to cirrhosis and cancer. A common variant in the gene PNPLA3, encoding the protein PNPLA3-I148M, is the strongest known genetic risk factor for MASLD to date. Despite its discovery twenty years ago, the function of PNPLA3, and now the role of PNPLA3-I148M, remain unclear. In this study, we sought to dissect the biogenesis of PNPLA3 and PNPLA3-I148M and characterize changes induced by endogenous expression of the disease-causing variant. Contrary to bioinformatic predictions and prior studies with overexpressed proteins, we demonstrate here that PNPLA3 and PNPLA3-I148M are not endoplasmic reticulum-resident transmembrane proteins. To identify their intracellular associations, we generated a paired set of isogenic human hepatoma cells expressing PNPLA3 and PNPLA3-I148M at endogenous levels. Both proteins were enriched in lipid droplet, Golgi, and endosomal fractions. Purified PNPLA3 and PNPLA3-I148M proteins associated with phosphoinositides commonly found in these compartments. Despite a similar fractionation pattern as the wild-type variant, PNPLA3-I148M induced morphological changes in the Golgi apparatus, including increased lipid droplet-Golgi contact sites, which were also observed in I148M-expressing primary human patient hepatocytes. In addition to lipid droplet accumulation, PNPLA3-I148M expression caused significant proteomic and transcriptomic changes that resembled all stages of liver disease. Cumulatively, we validate an endogenous human cellular system for investigating PNPLA3-I148M biology and identify the Golgi apparatus as a central hub of PNPLA3-I148M-driven cellular change.
2024-04-10 | PXD046335 | Pride