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Multiomic Profile Integration Reveals Early Signatures of Amyotrophic Lateral Sclerosis and Suggests the MAPK Pathway as a Therapeutic Target

ABSTRACT: Multiomic Profile Integration Reveals Early Signatures of Amyotrophic Lateral Sclerosis and Suggests the MAPK Pathway as a Therapeutic Target

PROVIDER: PRJNA980613 | ENA |

REPOSITORIES: ENA

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Multiomic Profile Integration Reveals Early Signatures of Amyotrophic Lateral Sclerosis and Suggests the MAPK Pathway as a Therapeutic Target

Project description:Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease and still lacks effective disease-modifying treatments. Here, we performed a multiomic analysis of the prefrontal cortex from 51 sporadic ALS patients and 50 control subjects, as well as from four transgenic mouse models of C9orf72-, SOD1-, TDP-43-, and FUS-ALS to characterize early disease mechanisms in ALS. An integrated analysis of transcriptomes, (phospho-)proteomes, and miRNAomes revealed marked sex-specific differences, more pronounced in males. We identified four transcriptome-based sALS-subclusters that are driven by pathways involved in mitochondrial respiration, synaptic function, immune response and transcription. Diffusion pseudo time estimation suggested that these clusters may represent temporal states in disease progression. Individual omics and multifactorial factor analysis revealed the mitogen-activated protein kinase (MAPK) pathway as a disease-relevant mechanism. Its modulation by trametinib in vitro and in vivo validated MEK2 as an auspicious therapeutic target for a subgroup of ALS patients.

2024-05-16 | PXD043300 | Pride

Multiomic Profile Integration Reveals Early Signatures of Amyotrophic Lateral Sclerosis and Suggests the MAPK Pathway as a Therapeutic Target

2024-05-16 | PXD051889 | Pride

Multiomic Profile Integration Reveals Early Signatures of Amyotrophic Lateral Sclerosis and Suggests the MAPK Pathway as a Therapeutic Target

2024-05-16 | PXD043297 | Pride

Multiomic Profile Integration Reveals Early Signatures of Amyotrophic Lateral Sclerosis and Suggests the MAPK Pathway as a Therapeutic Target [miRNA-Seq]

Project description:Multiomic Profile Integration Reveals Early Signatures of Amyotrophic Lateral Sclerosis and Suggests the MAPK Pathway as a Therapeutic Target [miRNA-Seq]

| PRJNA980615 | ENA

Multiomic Profile Integration Reveals Early Signatures of Amyotrophic Lateral Sclerosis and Suggests the MAPK Pathway as a Therapeutic Target [RNA-Seq]

Project description:Multiomic Profile Integration Reveals Early Signatures of Amyotrophic Lateral Sclerosis and Suggests the MAPK Pathway as a Therapeutic Target [RNA-Seq]

| PRJNA980618 | ENA

Sporadic Amyotrophic Lateral Sclerosis Study

Project description:Sporadic Amyotrophic Lateral Sclerosis Study

| PRJNA310034 | ENA

Multiomic Profile Integration Reveals Early Signatures of Amyotrophic Lateral Sclerosis and Suggests the MAPK Pathway as a Therapeutic Target [RNA-Seq]

Project description:The study conducted a multiomic analysis of the prefrontal cortex from 51 sporadic ALS patients and 50 control subjects, as well as four transgenic mouse models ( C9orf72, SOD1, TDP-43 and FUS) of ALS with each 5 males/females and 5 case/control samples. The analysis identified sex-specific differences in early disease mechanisms.

2024-04-22 | GSE234245 | GEO

Multiomic Profile Integration Reveals Early Signatures of Amyotrophic Lateral Sclerosis and Suggests the MAPK Pathway as a Therapeutic Target [miRNA-Seq]

2024-04-22 | GSE234243 | GEO

Amyotrophic lateral sclerosis

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

Amyotrophic lateral sclerosis: SOD1 mouse model

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

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