News
SWS: 2+1, ECTS: 5
Lecturer: Alexander Bockmayr
Tutor: Annika Röhl
Language: English / German
Dates
Lecture: 
Thursday 1416h 
Arnimallee 6 SR 025/026 
Exercise (every two weeks): 
Thursday 1618h 
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 constraintbased analysis of genomescale metabolic networks, with applications to systems biology and biotechnology.
We will discuss the steadystate 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 mixedinteger optimisation methods.
Schedule (subject to change)
Date 
Type 
Lecturer 
Topic 
Lecture Material 
Additional Material 
21.04.2016 
Lecture 
Bockmayr 
Introduction 
Slides 
Article 
28.04.2016 
Lecture Exercises 
Bockmayr Röhl 
FBA, FVA 
Slides Exercises 
Article 
05.05.2016 
Holiday 




12.05.2016 
Lecture 
Bockmayr 
FCA 
Slides 
Article 
19.05.2016 
Lecture Exercises 
Bockmayr Röhl 
EFMs 
Slides Exercise 

26.05.2016 
Lecture 
Bockmayr 
EFMs (ctd) 
Slides 
Article 
02.06.2016 
Lecture Lecture 
Bockmayr Bockmayr 
Targeted EFMs 
Slides 
Article 
09.06.2016 
Exercises 
Röhl 



16.06.2016 
Lecture Exercises 
Bockmayr Röhl 
Flux cone 
Slides 
Article 
23.06.2016 
Lecture Lecture 
Bockmayr Bockmayr 
MMBs rFBA 
Slides Slides 
Article Article Article 
30.06.2016 
Exercises 
Röhl 



07.07.2016 
Lecture 
Bockmayr 
Sequential phases 
Slides 
Article 
14.07.2016 
Lecture Exercises 
Bockmayr Röhl 
Sequential activation 
Slides 
Article 
21.07.2016 
Lecture 
Bockmayr 
Dynamic enzymecost FBA 
Slides 
Article 
Materials
Lewis NE, Nagarajan H, Palsson BO.
Constraining the metabolic genotypephenotype relationship using a phylogeny of in silico methods.
Nat Rev Microbiol., 10(4):291305, 2012.
Orth JD, Thiele I, Palsson BØ.
What is flux balance analysis? Nat Biotechnol., 28(3):2458, 2010.
Larhlimi A, David L, Selbig J, Bockmayr A.
F2C2: a fast tool for the computation of flux coupling in genomescale metabolic networks. BMC Bioinformatics 13:57, 2012
de Figueiredo LF, Podhorski A, Rubio A, Kaleta C, Beasley JE, Schuster S, Planes FJ.
Computing the shortest elementary flux modes in genomescale metabolic networks. Bioinformatics. 2009 Dec 1;25(23):315865
Rezola A, de Figueiredo LF, Brock M, Pey J, Podhorski A, Wittmann C, Schuster S, Bockmayr A, Planes FJ
Exploring metabolic pathways in genomescale networks via generating flux modes. Bioinformatics, 27/4, 534540, 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, 10991107, Nov/Dec 2014
Larhlimi A, Bockmayr A.
A new constraintbased description of the steadystate flux cone of metabolic networks. Discrete Applied Mathematics, 157, 22572266, 2009
Covert MW, Schilling CH, Palsson B.
Regulation of gene expression in flux balance models of metabolism. J Theor Biol. 2001 Nov 7;213(1):7388
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):204450
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
Klipp E, Heinrich R, Holzhütter HG.
Prediction of temporal gene expression. Metabolic opimization by redistribution of enzyme activities.
Eur J Biochem. 2002 Nov;269(22):540613
Waldherr S, Oyarzún DA, Bockmayr A.
Dynamic optimization of metabolic networks coupled with gene expression. Journal of Theoretical Biology, 365, 469485, Jan 2015
Minimum requirements
Active and regular participation at the exercises
Tutorial
Please sign in for the mailing list to get short term informations about the tutorials :
https://lists.fuberlin.de/listinfo/MetabolicNetworksSS16
Exercises:
Find the
first programming exercise
here. Deadline:
Tuesday, 17.05.2016, 08:00 a.m.
Find the
second programming exercise
here. Deadline:
Tuesday, 31.05.2016, 08:00 a.m.
Find the
third programming exercise
here. Deadline:
Tuesday, 14.06.2016, 08:00 a.m.
Find the
fourth programming exercise
here. Deadline:
Tuesday, 28.06.2016, 08:00 a.m.
Find the
fifth programming exercise
here. Deadline:
Tuesday, 12.07.2016, 08:00 a.m.
Sixth exercise: read the
article and focus on one example. Explain this example in the tutorial (Thursday 14.07.2016).
Example 2: Stefan, Sara, Svenja
Example 3: Hamid, Mathis, Arsene
Example 4: Parnika, Javier, Dennis
Points:
1 point: program contains critical errors
2 points: program contains small errors
3 points: program runs without errors
4 points: program runs without errors and you send me some extra explanation (what is the program good for). Not for every program.
For Aktive Teilnahme it is necessary to attend the tutorial and to do the homework (50% of the points in the end)
To get access to the additional material (including slides), please send an email including your zedataccountname to Annika Röhl:
annika.roehl@fuberlin.de