PXD007985-1

PXD007985 is an original dataset announced via ProteomeXchange.

Title	Deep Multilayer Tissue Proteomics Identifies Molecular Networks in Alzheimer’s Disease Progression, human data
Description	The molecular networks underlying Alzheimer’s disease (AD) are not well-defined. We present temporal profiling of 14,513 proteins and 34,173 phosphosites at the asymptomatic and symptomatic stages of AD, deep proteomics analysis of transgenic mouse models (5xFAD and Tau P301S), and computational algorithms for integrating multi-omics datasets. Network analysis reveals disease stage-correlated modules comprised of 218 proteins and 398 phosphoproteins differentially expressed in AD, as well as Aβ- or phospho-Tau-induced proteomic alterations. Cross-species comparison indicates that the 5xFAD model displays a similar molecular signature to symptomatic AD, but exhibits mouse-specific activation of interferon response, and lacks human-specific events, such as downregulation of neurotrophic factors (e.g. BDNF, VGF, CRH and Neuritin) and deregulation of iron homeostasis. Multi-omics integration prioritizes altered novel molecules and pathways, including inflammation, WNT signaling, TGFβ/BMP signaling, and membrane transport, which are enriched in secreted and cell surface proteins with heparin-binding domains. The top-ranked Aβ-Netrin-UNC5C axis shows a protective feedback in the asymptomatic stage. Thus, the multilayer proteomics and systems biology approaches elucidate disease networks/pathways in AD progression.
HostingRepository	PRIDE
AnnounceDate	2019-11-11
AnnouncementXML	Submission_2019-11-11_01:59:02.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	xusheng wang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue
Instrument	Q Exactive; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2017-10-17 08:21:56	ID requested
⏵ 1	2019-11-11 01:59:03	announced
2	2019-11-26 05:37:14	announced	2019-11-26: Updated project metadata.
3	2020-09-28 01:26:48	announced	2019-11-26: Updated project metadata. 2020-09-28: Updated publication reference for PubMed record(s): 31926610.

Dataset with its publication pending

curator keyword: Biomedical

submitter keyword: Alzheimer’s disease

mass spectrometry

proteomics

proteome

phosphoproteome

transcriptome

RNA-seq

genomics

genome

systems biology

disease network

Aβ

Tau

netrin

Junmin Peng
contact affiliation	St. Jude Children's Research Hospital
contact email	junmin.peng@stjude.org
lab head
xusheng wang
contact affiliation	Proteomics
contact email	xushengwang78@gmail.com
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/2019/11/PXD007985

PRIDE project URI

• PRIDE
  1. PXD007985
     1. Label: PRIDE project
     2. Name: Deep Multilayer Tissue Proteomics Identifies Molecular Networks in Alzheimer’s Disease Progression, human data