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However, efforts to expand the user base are impeded by hurdles in correctly formulating these problems to obtain numerical solutions. As numerous reviews of the field show, this approach and methodology has proven to be successful in studying a wide range of biological phenomena (McCloskey et al, 2013 Bordbar et al, 2014). 33 Institute for Computational and Mathematical Engineering, Stanford University, Stanford, CA, USAĬonstraint-based analysis of genome-scale models (GEMs) arose shortly after the first genome sequences became available.32 Department of Biological Systems Engineering, Virginia Tech, Blacksburg, VA, USA.31 Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, USA.30 Institute for Systems Biology, Seattle, WA, USA.29 European Molecular Biology Laboratory, Heidelberg, Germany.28 Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.27 Synthetic and Systems Biology Unit, Biological Research Center, Szeged, Hungary.26 Department of Environmental Biology, Centro de Investigaciones Biológicas (CSIC), Madrid, Spain.25 Australian Institute for Bioengineering & Nanotechnology (AIBN), The University of Queensland, Brisbane, Queensland, Australia.24 Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.23 Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, CA, USA.22 Department of Chemical Engineering, Pennsylvania State University, University Park, PA, USA.21 Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada.20 Department of Management Science and Engineering, Stanford University, Stanford, CA, USA.

19 Department of Pediatrics, University of California, San Diego, CA, USA.

17 Department of Chemical and Biomolecular Engineering (BK21 Plus Program), Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.

16 Institute of Engineering in Medicine, University of California, San Diego, CA, USA.

15 Department of Radiology, University of California, Los Angeles, CA, USA.

14 Department of Biological Engineering, Utah State University, Logan, UT, USA.

13 Department of Computing and Mathematical Science, California Institute of Technology, Pasadena, CA, USA.

12 Department of Mathematics, Rose-Hulman Institute of Technology, Terre Haute, IN, USA.

11 The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.

10 Laboratory of Computational Systems Biotechnology, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.

9 Department of Chemical and Life Science Engineering, Virginia Commonwealth University, Richmond, VA, USA.

7 Center for Bioinformatics Tuebingen (ZBIT), University of Tuebingen, Tübingen, Germany.

6 Department of Systems Biology, Harvard Medical School, Boston, MA, USA.

4 Sinopia Biosciences Inc., San Diego, CA, USA.

3 Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belval, Luxembourg.

2 Department of Biotechnology, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

1 Department of Bioengineering, University of California, San Diego, CA, USA.

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