Evidence map›Paper›PMID 24367245›Full record

ArticlePLoS computational biology2013

Perturbation biology: inferring signaling networks in cellular systems.

Evan J Molinelli, Anil Korkut, Weiqing Wang, Martin L Miller, Nicholas P Gauthier, Xiaohong Jing, Poorvi Kaushik, Qin He, Gordon Mills, David B Solit and 6 more

Abstract read
In one paragraph

Article in PLoS computational biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing 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

75 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Hypoxia alters the response of ovarian cancer cells to the mitomycin C drug.Frontiers in cell and developmental biology · 2025
    Article
  9. Machine learning to dissect perturbations in complex cellular systems.Computational and structural biotechnology journal · 2025
    Review
  10. Article
  11. Article
  12. Graph Structured Neural Networks for Perturbation Biology.bioRxiv : the preprint server for biology · 2024
    Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Network inference from perturbation time course data.NPJ systems biology and applications · 2022
    Article
  20. Article

15 more citing papers are in PubMed but not listed here.

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

16 authors.

Evan J MolinelliComputational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America ; Tri-Institutional Program for Computational Biology and Medicine, Weill Cornell Medical College, New York, New York, United States of America.
Anil KorkutComputational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
Weiqing WangComputational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
Martin L MillerComputational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
Nicholas P GauthierComputational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
Xiaohong JingComputational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
Poorvi KaushikComputational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America ; Tri-Institutional Program for Computational Biology and Medicine, Weill Cornell Medical College, New York, New York, United States of America.
Qin HeComputational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
Gordon MillsDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
David B SolitProgram in Molecular Pharmacology, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America ; Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
Christine A PratilasProgram in Molecular Pharmacology, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America ; Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
Martin WeigtLaboratoire de Génomique des Microorganismes, Université Pierre et Marie Curie, Paris, France.
Alfredo BraunsteinPolitecnico di Torino and Human Genetics Foundation, HuGeF, Torino, Italy.
Andrea PagnaniPolitecnico di Torino and Human Genetics Foundation, HuGeF, Torino, Italy.
Riccardo ZecchinaPolitecnico di Torino and Human Genetics Foundation, HuGeF, Torino, Italy.
Chris SanderComputational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Targeting the PI3K Signaling Pathway in Endometrial CarcinomaP50CA098258 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BROADDUS, RUSSELL R · 2003 to 2020
$32.0M
TR&D 3 - Network Guided Machine LearningP41GM103504 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY · 2012 to 2024
$17.3M
Variability of Cellular Responses to Growth Factors and Drugs During TumorgenesisU54CA148967 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ALTAN-BONNET, GREGOIRE · 2010 to 2014
$13.8M
Pathway Commons: Research Resource for Biological PathwaysU41HG006623 · NHGRI · SLOAN-KETTERING INST CAN RESEARCH · PI SANDER, CHRIS · 2012 to 2017
$5.7M
Tri-Institutional Training Program in Computational Biology & MedicineT32GM083937 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHRISTINI, DAVID J. · 2009 to 2018
$3.1M
NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA098258NCI NIH HHS U54 CA148967NCI NIH HHS U54CA148967NHGRI NIH HHS U41 HG006623NHGRI NIH HHS U41HG006623NIGMS NIH HHS GM103504NIGMS NIH HHS P41 GM103504NIGMS NIH HHS T32 GM083937NIGMS NIH HHS T32GM083937
6 · The paper itself

Abstract

We present a powerful experimental-computational technology for inferring network models that predict the response of cells to perturbations, and that may be useful in the design of combinatorial therapy against cancer. The experiments are systematic series of perturbations of cancer cell lines by targeted drugs, singly or in combination. The response to perturbation is quantified in terms of relative changes in the measured levels of proteins, phospho-proteins and cellular phenotypes such as viability. Computational network models are derived de novo, i.e., without prior knowledge of signaling pathways, and are based on simple non-linear differential equations. The prohibitively large solution space of all possible network models is explored efficiently using a probabilistic algorithm, Belief Propagation (BP), which is three orders of magnitude faster than standard Monte Carlo methods. Explicit executable models are derived for a set of perturbation experiments in SKMEL-133 melanoma cell lines, which are resistant to the therapeutically important inhibitor of RAF kinase. The resulting network models reproduce and extend known pathway biology. They empower potential discoveries of new molecular interactions and predict efficacious novel drug perturbations, such as the inhibition of PLK1, which is verified experimentally. This technology is suitable for application to larger systems in diverse areas of molecular biology.

Indexed as

Models, BiologicalSignal TransductionSystems BiologyCell Line, TumorHumansMonte Carlo MethodProbability

Identifiers

PMID24367245
PMCPMC3868523

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.