Evidence mapPaperPMID 29226804Full record

ArticleCell systems2017

Systems Pharmacology Dissection of Cholesterol Regulation Reveals Determinants of Large Pharmacodynamic Variability between Cell Lines.

Peter Blattmann, David Henriques, Michael Zimmermann, Fabian Frommelt, Uwe Sauer, Julio Saez-Rodriguez, Ruedi Aebersold

Abstract read
In one paragraph

Article in Cell systems, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

  1. Article
  2. Article
  3. Understanding the molecular diversity of synapses.Nature reviews. Neuroscience · 2025
    Review
  4. Article
  5. Article
  6. Leveraging gene correlations in single cell transcriptomic data.bioRxiv : the preprint server for biology · 2023
    Article
  7. Machine Learning and Hybrid Methods for Metabolic Pathway Modeling.Methods in molecular biology (Clifton, N.J.) · 2023
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Peter BlattmannDepartment of Biology, Institute of Molecular Systems Biology, ETH Zurich, Auguste-Piccard-Hof 1, 8093 Zurich, Switzerland. Electronic address: blattmann@imsb.biol.ethz.ch.
David HenriquesIIM-CSIC Spanish Council for Scientific Research, (Bio)Process Engineering Group, C/Eduardo Cabello 6, 36208 Vigo, Spain.
Michael ZimmermannDepartment of Biology, Institute of Molecular Systems Biology, ETH Zurich, Auguste-Piccard-Hof 1, 8093 Zurich, Switzerland.
Fabian FrommeltDepartment of Biology, Institute of Molecular Systems Biology, ETH Zurich, Auguste-Piccard-Hof 1, 8093 Zurich, Switzerland.
Uwe SauerDepartment of Biology, Institute of Molecular Systems Biology, ETH Zurich, Auguste-Piccard-Hof 1, 8093 Zurich, Switzerland.
Julio Saez-RodriguezRWTH-Aachen University, Faculty of Medicine, Joint Research Centre for Computational Biomedicine (JRC-COMBINE), MTZ Pauwelstrasse 19, D-52074 Aachen, Germany; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
Ruedi AebersoldDepartment of Biology, Institute of Molecular Systems Biology, ETH Zurich, Auguste-Piccard-Hof 1, 8093 Zurich, Switzerland; Faculty of Science, University of Zurich, Zurich, Switzerland. Electronic address: aebersold@imsb.biol.ethz.ch.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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 clinical setting. 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.

Indexed as

Drug ResistanceModels, BiologicalPharmacologySystems AnalysisAnimalsCell LineCholesterolHumansMass SpectrometryPhenotypeSystems IntegrationCholesterolGW3965logic modelingLXRmass spectrometrymetabolomicsproteomicsSREBPstatinsSWATHT0901317

Identifiers

PMID29226804
PMCPMC5747350

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.