PXD043300

PXD043300 is an original dataset announced via ProteomeXchange.

Title	Multiomic Profile Integration Reveals Early Signatures of Amyotrophic Lateral Sclerosis and Suggests the MAPK Pathway as a Therapeutic Target
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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:39:32.498.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD043300
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Marie GEBELIN
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-26 04:17:40	ID requested
1	2024-05-16 04:46:29	announced
⏵ 2	2024-10-22 06:39:32	announced	2024-10-22: Updated project metadata.

10.1101/2023.08.14.553180;

10.6019/PXD043300;

submitter keyword: Phosphoproteomics, Data Dependent Analysis (DDA),Proteomics, Amyotrophic Lateral Sclerosis (ALS), Multi-omic

Christine Carapito
contact affiliation	Laboratoire de Spectrométrie de Masse BioOrganique, IPHC UMR 7178, CNRS, Université de Strasbourg, Infrastructure Nationale de Protéomique ProFI - FR 2048, Strasbourg, France
contact email	ccarapito@unistra.fr
lab head
Marie GEBELIN
contact affiliation	Laboratoire de Spectometrie de Mass Bio-Organique, IPHC, CNRS
contact email	marie.gebelin@etu.unistra.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043300
     1. Label: PRIDE project
     2. Name: Multiomic Profile Integration Reveals Early Signatures of Amyotrophic Lateral Sclerosis and Suggests the MAPK Pathway as a Therapeutic Target