Evidence map›Paper›PMID 22737066›Full record

SynthesisPLoS computational biology2012

MC EMiNEM maps the interaction landscape of the Mediator.

Theresa Niederberger, Stefanie Etzold, Michael Lidschreiber, Kerstin C Maier, Dietmar E Martin, Holger Fröhlich, Patrick Cramer, Achim Tresch

Open access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in PLoS computational biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.3field-weighted citation impact, top 20% of its field
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

10 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Context-Specific Nested Effects Models.Journal of computational biology : a journal of computational molecular cell biology · 2020
    Article
  3. DRUG-NEM: Optimizing drug combinations using single-cell perturbation response to account for intratumoral heterogeneity.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  4. Context-Specific Nested Effects Models.Research in computational molecular biology : ... Annual International Conference, RECOMB ... : proceedings. RECOMB (Conference : 2005- ) · 2018
    Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Considering unknown unknowns: reconstruction of nonconfoundable causal relations in biological networks.Journal of computational biology : a journal of computational molecular cell biology · 2013
    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

8 authors at 4 institutions in 1 country.

Theresa NiederbergerGene Center Munich and Center for integrated Protein Science CiPSM, Department of Biochemistry, Ludwig-Maximilians-University Munich, Munich, Germany.
Stefanie Etzold
Michael Lidschreiber
Kerstin C Maier
Dietmar E Martin
Holger Fröhlich
Patrick Cramer
Achim Tresch
Ludwig-Maximilians-Universität München · DECenter for Integrated Protein Science Munich · DEBonn Aachen International Center for Information Technology · DEUniversity of Cologne · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The Mediator is a highly conserved, large multiprotein complex that is involved essentially in the regulation of eukaryotic mRNA transcription. It acts as a general transcription factor by integrating regulatory signals from gene-specific activators or repressors to the RNA Polymerase II. The internal network of interactions between Mediator subunits that conveys these signals is largely unknown. Here, we introduce MC EMiNEM, a novel method for the retrieval of functional dependencies between proteins that have pleiotropic effects on mRNA transcription. MC EMiNEM is based on Nested Effects Models (NEMs), a class of probabilistic graphical models that extends the idea of hierarchical clustering. It combines mode-hopping Monte Carlo (MC) sampling with an Expectation-Maximization (EM) algorithm for NEMs to increase sensitivity compared to existing methods. A meta-analysis of four Mediator perturbation studies in Saccharomyces cerevisiae, three of which are unpublished, provides new insight into the Mediator signaling network. In addition to the known modular organization of the Mediator subunits, MC EMiNEM reveals a hierarchical ordering of its internal information flow, which is putatively transmitted through structural changes within the complex. We identify the N-terminus of Med7 as a peripheral entity, entailing only local structural changes upon perturbation, while the C-terminus of Med7 and Med19 appear to play a central role. MC EMiNEM associates Mediator subunits to most directly affected genes, which, in conjunction with gene set enrichment analysis, allows us to construct an interaction map of Mediator subunits and transcription factors.

Indexed as

AlgorithmsBayes TheoremComputational BiologyComputer SimulationGene Expression ProfilingMediator ComplexModels, BiologicalModels, StatisticalMonte Carlo MethodProtein Interaction MappingSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsMediator ComplexSaccharomyces cerevisiae Proteins

Identifiers

PMID22737066
PMCPMC3380870
OpenAlexW2069412330

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.