PXD005955

PXD005955 is an original dataset announced via ProteomeXchange.

Title	Systems pharmacology dissection of cholesterol regulation reveals determinants of large pharmacodynamic variability between cell lines
Description	In individuals, heterogeneous drug response phenotypes result from a complex interplay of dose, drug specificity, genetic background, and environmental factors, thus challenging our understanding of the underlying processes and optimal use of drugs in the clinic. Here, we use mass spectrometry-based quantification of molecular response phenotypes and logic modeling to explain drug response differences in a panel of cell lines. We apply this approach to cellular cholesterol regulation, a biological process with high clinical relevance. From the quantified molecular phenotypes elicited by various targeted pharmacologic or genetic treatments, we generated cell-line-specific models that quantified the processes beneath the idiotypic intracellular drug responses. The models revealed that in addition to drug uptake and metabolism further cellular processes displayed significant pharmacodynamic response variability between the cell lines, resulting in cell-line-specific drug response phenotypes. This study demonstrates the importance of integrating different types of quantitative systems-level molecular measurements with modeling to understand the effect of pharmacological perturbations on complex biological processes.
HostingRepository	PRIDE
AnnounceDate	2017-12-07
AnnouncementXML	Submission_2018-05-23_07:00:41.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Peter Blattmann
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2017-02-23 01:23:09	ID requested
1	2017-12-07 03:33:07	announced
⏵ 2	2018-05-23 07:00:43	announced	Updated publication reference for PubMed record(s): 29226804.

Blattmann P, Henriques D, Zimmermann M, Frommelt F, Sauer U, Saez-Rodriguez J, Aebersold R, Systems Pharmacology Dissection of Cholesterol Regulation Reveals Determinants of Large Pharmacodynamic Variability between Cell Lines. Cell Syst, 5(6):604-619.e7(2017) [pubmed]

curator keyword: Biomedical

submitter keyword: cholesterol homeostasis, cholesterol regulation, HEK293, Hela Kyoto, Huh7, HepG2, SREBP, SREBP1, SREBP2, HMGCS1, LDLR, NPC1, LXR, atorvastatin, T0901317, GW3965

Ruedi Aebersold
contact affiliation	1) Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Switzerland 2) Faculty of Science, University of Zurich, Zurich, Switzerland
contact email	aebersold@imsb.biol.ethz.ch
lab head
Peter Blattmann
contact affiliation	ETH Zurich
contact email	blattmann@imsb.biol.ethz.ch
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/2017/12/PXD005955

PRIDE project URI

• PRIDE
  1. PXD005955
     1. Label: PRIDE project
     2. Name: Systems pharmacology dissection of cholesterol regulation reveals determinants of large pharmacodynamic variability between cell lines