Open Access Highly Accessed Research article

Network topology and parameter estimation: from experimental design methods to gene regulatory network kinetics using a community based approach

Pablo Meyer1*, Thomas Cokelaer2, Deepak Chandran3, Kyung Hyuk Kim4, Po-Ru Loh5, George Tucker5, Mark Lipson5, Bonnie Berger5, Clemens Kreutz8, Andreas Raue78, Bernhard Steiert8, Jens Timmer68, Erhan Bilal1, DREAM 6&7 Parameter Estimation consortium, Herbert M Sauro4, Gustavo Stolovitzky1 and Julio Saez-Rodriguez2*

Author Affiliations

1 T.J. Watson Research Center, Yorktown Heights, New York, USA

2 European Molecular Biology Laboratory, European Bioinformatics Institute, Cambridge, UK

3 Autodesk Research, San Francisco, CA, USA

4 Department of Bioengineering, University of Washington, William H. Foege Building, Box 355061, Seattle, WA 98195-5061, USA

5 Department of Mathematics, MIT, Cambridge, Massachusetts, USA

6 BIOSS Centre for Biological Signalling Studies, University of Freiburg, Schänzlestr. 18, 79104 Freiburg, Germany

7 Merrimack Pharmaceuticals One Kendall Square, Suite B7201, Cambridge, MA 02139, USA

8 Physics Department, University of Freiburg, Hermann-Herder Str.3, 79104 Freiburg, Germany

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BMC Systems Biology 2014, 8:13  doi:10.1186/1752-0509-8-13

Published: 7 February 2014

Additional files

Additional file 1:

Supplementary material files– Models and Submissions – model and data for challenge are provided as supplementary material as well as participants’ submissions. Models are provided in MATLAB and Systems Biology Markup Language (SBML format) and the submissions name reflects the rank except for the best performing teams. They are also available at the DREAM site (http://www.the-dream-project.org/challenges/network-topology-and-parameter-inference-challenge webcite).

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Additional file 2: Figure S2:

Network topology challenge gene network and scores A. Gene network for model 2 of 11 genes and 45 parameters where links r9, r10, r12 were missing and whose identity challenge participants had to determine. B. A score is calculated based on the 3 different links predicted and a p-value is calculated based on the distribution of randomly generated links used as a null-hypothesis (see main text).

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Additional file 3: Figure S1:

Score calculation of the Parameter Estimation Challenge. A. A distance as shown by the equation is calculated based on the 45 parameters predicted values and a p-value is calculated when compared to a distribution of randomly generated relative null-hypothesis. B. A distance as shown by the equation is calculated based on the predicted protein concentration value for p3, p5 and p8 and a p-value is calculated when compared to a distribution of randomly generated relative null-hypothesis.

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Additional file 4: Table S1:

Summary of the experimental design considerations of team crux for the network inference challenge. The second column denotes the chosen experimental conditions in the notation used during the challenge. The arguments underlying their decisions are denoted by abbreviations. Wild-type measurements provide data for substantially fewer credits (argument “WT”). Such measurements have been chosen initially to obtain a setting with a reasonable set of identifiable parameters. Data with high resolution over time (argument “High-Res”) provides more detailed information about the dynamics and was therefore expected to be more efficient for distinguishing potentially missing links with similar qualitative effects. Using a measurement technique providing data for all compounds (argument “All”) is advantageous to obtain a comprehensive overview of the effect of a perturbation. The argument abbreviated by “Range” indicates the fact that missing links are only identifiable, if the concentration range of the regulator is not far from the respective Michaelis constant Kd. Therefore we performed perturbations affecting the concentration range of potential regulators in a desired direction. Finally, we had to take into account the remaining credits indicated by the argument “Budget”.

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Additional file 5: Table S2:

Table used to score the submitted links for network topology challenge A link is defined by a source and a destination gene, and a source gene may or may not have two destination genes. Each row on the table represents a possible link submission. Ni represents the number of points given for the submitted link, where i stands for incorrect and c a correct prediction of the source and destination gene. Note that correct (+/−) predictions without the correct gene give no points.

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