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Predicting network modules of cell cycle regulators using relative protein abundance statistics

Overview of attention for article published in BMC Systems Biology, February 2017
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Title
Predicting network modules of cell cycle regulators using relative protein abundance statistics
Published in
BMC Systems Biology, February 2017
DOI 10.1186/s12918-017-0409-1
Pubmed ID
Authors

Cihan Oguz, Layne T. Watson, William T. Baumann, John J. Tyson

Abstract

Parameter estimation in systems biology is typically done by enforcing experimental observations through an objective function as the parameter space of a model is explored by numerical simulations. Past studies have shown that one usually finds a set of "feasible" parameter vectors that fit the available experimental data equally well, and that these alternative vectors can make different predictions under novel experimental conditions. In this study, we characterize the feasible region of a complex model of the budding yeast cell cycle under a large set of discrete experimental constraints in order to test whether the statistical features of relative protein abundance predictions are influenced by the topology of the cell cycle regulatory network. Using differential evolution, we generate an ensemble of feasible parameter vectors that reproduce the phenotypes (viable or inviable) of wild-type yeast cells and 110 mutant strains. We use this ensemble to predict the phenotypes of 129 mutant strains for which experimental data is not available. We identify 86 novel mutants that are predicted to be viable and then rank the cell cycle proteins in terms of their contributions to cumulative variability of relative protein abundance predictions. Proteins involved in "regulation of cell size" and "regulation of G1/S transition" contribute most to predictive variability, whereas proteins involved in "positive regulation of transcription involved in exit from mitosis," "mitotic spindle assembly checkpoint" and "negative regulation of cyclin-dependent protein kinase by cyclin degradation" contribute the least. These results suggest that the statistics of these predictions may be generating patterns specific to individual network modules (START, S/G2/M, and EXIT). To test this hypothesis, we develop random forest models for predicting the network modules of cell cycle regulators using relative abundance statistics as model inputs. Predictive performance is assessed by the areas under receiver operating characteristics curves (AUC). Our models generate an AUC range of 0.83-0.87 as opposed to randomized models with AUC values around 0.50. By using differential evolution and random forest modeling, we show that the model prediction statistics generate distinct network module-specific patterns within the cell cycle network.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 19 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 19 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 26%
Researcher 4 21%
Student > Bachelor 3 16%
Professor 3 16%
Professor > Associate Professor 2 11%
Other 2 11%
Readers by discipline Count As %
Agricultural and Biological Sciences 5 26%
Biochemistry, Genetics and Molecular Biology 4 21%
Engineering 2 11%
Medicine and Dentistry 2 11%
Social Sciences 1 5%
Other 3 16%
Unknown 2 11%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 March 2017.
All research outputs
#10,344,587
of 18,244,804 outputs
Outputs from BMC Systems Biology
#438
of 1,116 outputs
Outputs of similar age
#129,404
of 268,889 outputs
Outputs of similar age from BMC Systems Biology
#3
of 11 outputs
Altmetric has tracked 18,244,804 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,116 research outputs from this source. They receive a mean Attention Score of 3.5. This one has gotten more attention than average, scoring higher than 57% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 268,889 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.
We're also able to compare this research output to 11 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 81% of its contemporaries.