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DataSet Summary

  • HostingRepository: PRIDE
  • AnnounceDate: 2017-12-07
  • AnnouncementXML: Submission_2018-05-23_07:00:41.xml
  • DigitalObjectIdentifier:
  • ReviewLevel: Peer-reviewed dataset
  • DatasetOrigin: Original data
  • RepositorySupport: Unsupported dataset by repository
  • PrimarySubmitter: Peter Blattmann
  • 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.
  • SpeciesList: scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
  • ModificationList: phosphorylated residue
  • Instrument: TripleTOF 5600

Dataset History

VersionDatetimeStatusChangeLog Entry
02017-02-23 01:23:09ID requested
12017-12-07 03:33:07announced
22018-05-23 07:00:43announcedUpdated publication reference for PubMed record(s): 29226804.

Publication List

  1. 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]

Keyword List

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

Contact List

    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:

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