PXD041727

PXD041727 is an original dataset announced via ProteomeXchange.

Title	Presynaptic proteins in the orbitofrontal cortex predict Alcohol Use Disorder
Description	Alcohol use disorder (AUD) is a life-threatening disease characterized by compulsive drinking, cognitive deficits, and social impairment that continue despite negative consequences, which are driven by dysfunction of cortical areas, such as the orbitofrontal cortex (OFC), that normally balances decisions related to reward and risk. In this study, proteomics and machine learning analysis of post-mortem OFC brain samples collected from individuals with AUD revealed dysregulation of presynaptic (e.g., AP2A1) and mitochondrial proteins that predicted the occurrence and severity of AUD. Alcohol-sensitive OFC proteins also mapped to abnormal social behaviors and interactions. Validation using reverse genetics, we found that prefrontal Ap2a1 regulates alcohol drinking in genetically diverse mouse strains. Furthermore, we demonstrated sexual dimorphism in human OFC proteins that regulate extracellular matrix structure and signaling. Together, these findings highlight the impact of excessive alcohol consumption on the human OFC proteome and identify important cross-species cortical mechanisms underlying AUD.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:05:43.775.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Phillip Wilmarth
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-21 21:18:14	ID requested
1	2023-10-09 09:19:12	announced
⏵ 2	2023-11-14 09:05:44	announced	2023-11-14: Updated project metadata.

Mulholland PJ, Berto S, Wilmarth PA, McMahan C, Ball LE, Woodward JJ, Adaptor protein complex 2 in the orbitofrontal cortex predicts alcohol use disorder. Mol Psychiatry, 28(11):4766-4776(2023) [pubmed]

submitter keyword: machine learning, alcohol drinking, isobaric labeling,Alcohol use disorder, sexual dimorphism, mass spectrometry, AP2A1, orbitofrontal cortex, mitochondria, quantitative proteomics, presynapses, extracellular matrix

Patrick J. Mulholland, PhD
contact affiliation	Medical University of South Carolina Charleston Alcohol Research Center Department of Neuroscience and Psychiatry & Behavioral Sciences 30 Courtenay Drive, BM629C Charleston, SC 29425-8610 USA
contact email	mulholl@musc.edu
lab head
Phillip Wilmarth
contact affiliation	OHSU
contact email	wilmarth@ohsu.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/10/PXD041727

PRIDE project URI

• PRIDE
  1. PXD041727
     1. Label: PRIDE project
     2. Name: Presynaptic proteins in the orbitofrontal cortex predict Alcohol Use Disorder