PXD018218

PXD018218 is an original dataset announced via ProteomeXchange.

Title	Causal integration of multi-omics data with prior knowledge to generate mechanistic hypotheses
Description	The integration of multi-omic data sets can provide unique information about molecular processes in a cell. Despite the development of many tools to extract information from such data sets, there are limited strategies to systematically extract mechanistic hypotheses from them. We here present COSMOS (Causal Oriented Search of Multi-Omic Space), a method that integrates cell signaling pathways, transcriptional, and metabolics data sets. COSMOS leverages extensive prior knowledge of interactions between biomolecules with computational methods to estimate activities of transcription factors and kinases as well as network-level causal reasoning. COSMOS can provide mechanistic explanations for experimental observations across multiple omic data sets. We applied COSMOS to a dataset comprising transcriptomic, phosphoproteomic, and metabolomic data from nine renal cell carcinoma patients comparing healthy non affected kidney tissue and kidney cancer. We used COSMOS to generate novel hypotheses such as the impact of CDK7 on nucleoside metabolism and its influence on citrulline production, that we validated experimentally. We expect that our freely available method will be broadly useful to extract mechanistic insights from multi-omic studies.
HostingRepository	PRIDE
AnnounceDate	2021-02-02
AnnouncementXML	Submission_2021-02-02_04:20:27.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dorte Bekker-Jensen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-26 15:16:22	ID requested
⏵ 1	2021-02-02 04:20:28	announced

Dugourd A, Kuppe C, Sciacovelli M, Gjerga E, Gabor A, Emdal KB, Vieira V, Bekker-Jensen DB, Kranz J, Bindels EMJ, Costa ASH, Sousa A, Beltrao P, Rocha M, Olsen JV, Frezza C, Kramann R, Saez-Rodriguez J, Causal integration of multi-omics data with prior knowledge to generate mechanistic hypotheses. Mol Syst Biol, 17(1):e9730(2021) [pubmed]

submitter keyword: Q Exactive HF-X, Human, Kidney, Phosphorylation

Jesper V. Olsen
contact affiliation	Proteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
contact email	jesper.olsen@cpr.ku.dk
lab head
Dorte Bekker-Jensen
contact affiliation	University of Copenhagen
contact email	dorte.bekker-jensen@cpr.ku.dk
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/2021/02/PXD018218

PRIDE project URI

• PRIDE
  1. PXD018218
     1. Label: PRIDE project
     2. Name: Causal integration of multi-omics data with prior knowledge to generate mechanistic hypotheses