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)
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