Genome wide analysis points towards subtype specific diseases in different genetic forms of Amyotrophic Lateral Sclerosis
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ABSTRACT:
PROVIDER: PRJNA664621 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Sporadic Amyotrophic Lateral Sclerosis Study
| PRJNA310034 | ENA
Project description:We established iPSCs from healthy donors, FUS-ALS and SOD1-ALS patients. Using our differentiation protocol originally developed by Reinhardt et al.,2013, we diferentiated these iPSCs toward spinal motor neurons (MNs) and reproduce ALS pathology in a dish. To extend our understanding of finding different molecular mechanisms and pathways related to FUS- and SOD mutations in ALS disease, we have performed a comprehensive gene expression profiling study using microarray hybridization of the iPSC-derived MN models from control individuals and carefully compared with those from FUS-ALS and SOD1-ALS patients. In addition, we further analyzed previously published independent datasets containing the genome-wide RNA profiling of iPSC-derived MN samples from patients with FUS and SOD1 mutations and controls. This microaray dataset GSE10638 (Fujimori et al., 2018) was retrieved from GEO database and was screened to identifiy potential drug candidates which suppressed the detected ALS-related phenotypes of these ALS models. Finally, we made a systematic comparison with our results to the ones independently obtained previously.Here through this study, we create a gene profile of ALS by analyzing the differentially expressed genes (DEGs), the kyoto encyclopedia of Genes and Genomes (KEGG) pathways, the interactome as well as transcription factor profiles (TF) that would identify altered functional/molecular signatures and their interactions at both transcriptional (mRNAs) and translational levels (hub proteins and TFs) which stands validation across the different datasets (including different differentiation protocols etc.). By doing so we provide condensed pathophysiological pathways of FUS-ALS and SOD1-ALSto better understand the biological mechanisms underlying motor neuron disease.
2020-09-21 | GSE158264 | GEO
Project description:Identification of amyotrophic lateral sclerosis (ALS) associated genes. Post mortem spinal cord grey matter from sporadic and familial ALS patients compared with controls. Keywords: other
2003-11-14 | GSE833 | GEO
Project description:Amyotropic lateral sclerosis (ALS) is a lethally progressive and irreversible neurodegenerative disease marked by apparent death of motor neurons present in the spinal cord, brain stem and motor cortex. While more and more gene mutants being established for genetic ALS, the vast majority suffer from sporadic ALS (>90%). It has been challenging, thus, to model sporadic ALS which is one reason why the underlying pathophysiology remains elusive and has stalled the development of therapeutic strategies of this progressive motor neuron disease. To further unravel these pathological signaling pathways, human induced pluripotent stem cell (hiPSCs)-derived motor neurons (MNs) from FUS- and SOD1 ALS patients and healthy controls were systematically compared to independent published datasets. Here through this study we created a gene profile of ALS by analyzing the DEGs, the Kyoto encyclopedia of Genes and Genomes (KEGG) pathways, the interactome and the transcription factor profiles (TF) that would identify altered molecular/functional signatures and their interactions at both transcriptional (mRNAs) and translational levels (hub proteins and TFs). Our findings suggest that FUS and SOD1 may develop from dysregulation in several unique pathways and herpes simplex virus (HSV) infection was among the topmost predominant cellular pathways connected to FUS and not to SOD1. In contrast, SOD1 is mainly characterized by alterations in the metabolic pathways and alterations in the neuroactive-ligand-receptor interactions. This suggests that different genetic ALS forms are singular diseases rather than part of a common spectrum. This is important for patient stratification clearly pointing towards the need for individualized medicine approaches in ALS.
| S-EPMC7555318 | biostudies-literature
Project description:Identification of familial amyotrophic lateral sclerosis (fALS) related genes. Material from three hSOD1(G93A) transgenic mice was compared to material from three non-transgenic control mice using an alternating loop design on two-colour cDNA microarrays. Statistical data management and analysis: postgreSQL relational database (www.postgresql.org), Perl, and R (www.r-project.org); pin-wise lowess-regression based normalisation (Yang et al., 2002 [PMID: 11842121]); mixed ANOVA-model. Keywords = amyotrophic lateral sclerosis, ALS, SOD1 mouse model
2010-06-05 | E-GEOD-2400 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE39642: NanoString nCounter immune-related gene expression in blood sorted CD14+CD16- monocytes from sALS, fALS and HC subjects GSE39643: NanoString miRNA profiling of peripheral blood sorted CD14+CD16- monocytes from amyotrophic lateral sclerosis, multiple sclerosis and healthy control subjects Refer to individual Series
2012-07-25 | E-GEOD-39644 | biostudies-arrayexpress
Project description:Identification of familial amyotrophic lateral sclerosis (fALS) related genes. Material from three hSOD1(G93A) transgenic mice was compared to material from three non-transgenic control mice using an alternating loop design on two-colour cDNA microarrays. Statistical data management and analysis: postgreSQL relational database (www.postgresql.org), Perl, and R (www.r-project.org); pin-wise lowess-regression based normalisation (Yang et al., 2002 [PMID: 11842121]); mixed ANOVA-model. Keywords = amyotrophic lateral sclerosis, ALS, SOD1 mouse model Keywords: other
2005-12-31 | GSE2400 | GEO
Project description:This study was designed to identify gene expression changes in skeletal muscle that could define reliably the degree of the severity of Amyotrophic lateral sclerosis (ALS). All samples were from human biopsies, either from healthy muscles or from muscle whose patients were clearly diagnosed as having Amyotrophic Lateral Sclerosis (ALS)
2012-01-17 | E-MEXP-3260 | biostudies-arrayexpress
Project description:Spatiotemporal dynamics of molecular pathology in amyotrophic lateral sclerosis
2019-04-05 | GSE120374 | GEO
Project description:Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal disease. Although astrocytes are increasingly recognized contributors to the underlying pathogenesis, the uniformity of their reactive transformation in different genetic forms of ALS remains unresolved. Here we begin to systematically examine this issue by performing RNA sequencing on highly enriched and serum-free human induced pluripotent stem cell derived astrocytes from patients with VCP, SOD1 and FUS mutations. The RNA-seq samples in this collection have been used to reveal that diverse fALS mutations lead to molecularly distinct reactive transformation in their basal state.
2021-09-20 | E-MTAB-10916 | biostudies-arrayexpress