## News

SWS: 2+1, ECTS: 5

**Lecturer:** Alexander Bockmayr

**Tutor:** Therese Lorenz

**Language:** English / German

## Dates

Lecture: |
Thursday 14-16h |
Arnimallee 6 SR 025/026 |

Exercise (every two weeks): |
Thursday 16-18h |
Arnimallee 6 SR 025/026 |

## Contents

The goal of this course is to give an introduction to the most important mathematical and algorithmic ideas underlying the constraint-based analysis of genome-scale metabolic networks, with applications to systems biology and biotechnology.

We will discuss the steady-state flux cone, flux balance analysis (FBA), flux variability analysis (FVA), flux coupling analysis (FCA), elementary flux modes (EFMs), thermodynamic constraints, and metabolic regulation. On the algorithmic side, the focus will be on linear and mixed-integer optimisation methods.

## Schedule (subject to change)

Date |
Type |
Lecturer |
Topic |
Lecture Material |
Additional Material |

16.04.2015 |
Lecture |
Bockmayr |
Introduction |
Slides |
Article |

23.04.2015 |
Lecture Exercises |
Bockmayr Lorenz |
FBA, FVA, FCA |
Slides |
Article |

30.04.2015 |
Lecture |
Bockmayr |
FCA |
Slides |
Article |

07.05.2015 |
Lecture Exercises |
Bockmayr Lorenz |
EFMs |
Slides |
Article |

14.05.2015 |
Holiday |

21.05.2015 |
Lecture |
Bockmayr |
Targeted EFMs |
Slides |
Article |

28.05.2015 |
Lecture Exercises |
Bockmayr Lorenz |
Targeted EFMs (ctd) |

04.06.2015 |
Lecture |
Bockmayr |
Flux cone + MMBs |
Slides |

11.06.2015 |
Lecture Exercises |
Bockmayr Lorenz |
Sequential metabolic phases |
Slides |
Article |

18.06.2015 |
Lecture |
Bockmayr |
Regulatory FBA (rFBA) |
Slides |
Article Article |

25.06.2015 |
Lecture Exercises |
Bockmayr Lorenz |
Integrated FBA (iFBA) |
Slides |
Article Article |

02.07.2015 |
Lecture |
Bockmayr |
Temporal gene expression |
Slides |
Article |

09.07.2015 |
Exercises |
Lorenz |

16.07.2015 |
Lecture Lecture |
Bockmayr Bockmayr |
Dynamic enzyme-cost FBA (deFBA) |
Slides |
Article |

## Materials

Lewis NE, Nagarajan H, Palsson BO.

Constraining the metabolic genotype-phenotype relationship using a phylogeny of in silico methods.
Nat Rev Microbiol., 10(4):291-305, 2012.

Orth JD, Thiele I, Palsson BØ.

What is flux balance analysis? Nat Biotechnol., 28(3):245-8, 2010.

Larhlimi A, David L, Selbig J, Bockmayr A.

F2C2: a fast tool for the computation of flux coupling in genome-scale metabolic networks. BMC Bioinformatics 13:57, 2012

Rezola A, de Figueiredo LF, Brock M, Pey J, Podhorski A, Wittmann C, Schuster S, Bockmayr A, Planes FJ

Exploring metabolic pathways in genome-scale networks via generating flux modes. Bioinformatics, 27/4, 534-540, 2011

David L, Bockmayr A.

Computing elementary flux modes involving a set of target reactions. IEEE/ACM Transactions on Computational Biology and Bioinformatics, 11/6, 1099-1107, Nov/Dec 2014

Larhlimi A, Bockmayr A.

A new constraint-based description of the steady-state flux cone of metabolic networks. Discrete Applied Mathematics, 157, 2257-2266, 2009

Palinkas A, Bulik S, Bockmayr A, Holzhütter HG.

Sequential Metabolic Phases as a Means to Optimize Cellular Output in a Constant Environment. PLoS ONE, 10(3): e0118347, Mar 2015

Covert MW, Schilling CH, Palsson B.

Regulation of gene expression in flux balance models of metabolism. J Theor Biol. 2001 Nov 7;213(1):73-88

Covert MW, Xiao N, Chen TJ, Karr JR.

Integrating metabolic, transcriptional regulatory and signal transduction models in Escherichia coli. Bioinformatics. 2008 Sep 15;24(18):2044-50

Klipp E, Heinrich R, Holzhütter HG.

Prediction of temporal gene expression. Metabolic opimization by re-distribution of enzyme activities.
Eur J Biochem. 2002 Nov;269(22):5406-13

Waldherr S, Oyarzún DA, Bockmayr A.

Dynamic optimization of metabolic networks coupled with gene expression. Journal of Theoretical Biology, 365, 469-485, Jan 2015

## Minimum requirements

Active and regular attendance at exercises

## Tutorial

Please sign in for the mailinglist to get shortterm informations about the tutorials :

https://lists.fu-berlin.de/listinfo/MetabolicNetworksSS15
**Exercises:**
**Exercise sheet 1** (due 30.04.):

MetabolicNetworks_Ex1.pdf. The testing examples can be downloaded here:

MetabolicNetworks.zip
**Exercise sheet 2** (due 14.05.):

MetabolicNetworks_Ex2.pdf. The article needed for the last exercise is

F2C2 Article.

** Edited:** In Exercise 4d the inference rules are the transitivity rules of the coupling relations.

** Second chance:** Due 04.06.

**Exercise sheet 3** (due 18.06.):

MetabolicNetworks_Ex3.pdf.
The script of the tutorial:

DeFig.pdf.

The small testing examples can be downloaded here:

BeispielNetzwerke.zip, as more interesting examples use the examples of exercise 1.

**Be careful**: The small examples have individual names, instead of the standard name 'network', so your program may either accept a previously loaded struct as argument or determine the correct field name by using 'model = load('struct.mat'); names = fieldnames(model);'

Additional material :

Computing the shortest elementary flux modes in genome-scale metabolic networks by Luis de Figueiredo et al.

**Algorithm:** shortestEFMs.m
**Exercise sheet 4** :

MetabolicNetworks_Ex4.pdf. For the next tutorial you should read the this

Article and especially focus on your example (Ex. 1 - Marthe, Balduin; Ex. 2 - Marjan, Moritz; Ex. 3 - David, Pascal).

To get access to the additional material (including slides), please send an e-mail including your zedat-accountname to Therese Lorenz:

therese.lorenz@fu-berlin.de