Gen om e d iver si ty

Goals
Representing, analysing, and visualising biological networks 
and related data; visual analytics of multimodal biological data; 
modelling plant metabolism.
Research Report
We developed novel methods for analysing, modelling, and ex-
ploring biological data and networks which have been imple-
mented in our open-source system VANTED (M. klapperstück, 
h. Rohn - www.vanted.org). Vanted has been used in several 
in-house and external collaborations, for example, investiga-
ting metabolism in Hordeum vulgare, Arxula adeninivorans and 
Brassica napus to understand and improve metabolic processes 
(e. Grafahrend-belau, a. hartmann, a. Junker, M. klapperstück 

105
during the generative phase of Hordeum vulgare, as well as the 
diurnal cycles of photosynthesis of the Hordeum vulgare leaf 
(a. eschenröder, e. Grafahrend-belau, a. Junker, with research 
group Systems biology and research group heterosis). the 
MMM platform provides the basis for future in silico analyses 
of metabolic and physiological mechanisms controlling 
carbon partitioning, thereby contributing to the identification 
and optimization of strategies for the improve ment of yield 
formation in an important crop plant.
Standardisation methods in Systems biology have been further 
developed in an international collaboration with various part-
ners, including the Systems Biology Graphical Notation 
(SBGN), where several tools and resources were developed in 
the group which will facilitate the use of SbGn for biologists 
such as SbGn-ed, Metacrop SbGn-pathways, keGG SbGn- 
pathways, SbGn bricks, and LibSbGn (t. czauderna, a. Junker).
belau, a. hartmann, a. Junker with research group heterosis, 
research group Systems biology, and university halle). the 
models provide frameworks for studying metabolism in 
silico with flux balance analysis and related methods and 
allow predicting flux distributions and optimal metabolic 
capabilities under different environmental conditions and 
genetic backgrounds. Mathematical methods and models for 
multiscale modelling of metabolism (MMM) combining 
different modelling approaches have been further developed 
with the aim of achieving a spatio-temporal resolution of 
complex metabolic processes of crop plant metabolism 
organized on a whole-plant scale (see Fig. 32). MMM integrates 
static organ-specific models (source leaf, sink/source stem, 
seed, root) with a whole-plant dynamic model. allowing for 
a dynamic flux balance analysis on a whole-plant scale, the 
MMM approach was used to study source-sink interactions 
Fig. 32
Workflow of the multiscale metabolic modeling (MMM) approach to analyse the dynamic metabolism of barley. the MMM approach integrates a static multi-organ Fba 
model and a dynamic FPM to perform dynamic Fba. as a result the spatio-temporal metabolic behavior of the multi-organ Fba model is predicted by computing a series of 
steady-state solutions constrained by dynamic constraints predicted by the FPM. Fba: flux balance analysis; FPM: multiscale functional whole-plant model; MMM: multiscale 
metabolic modeling (e. Grafahrend-belau).

Abteilung Molekulare Genetik/
Department of Molecular Genetics
106
the identification and regulation of the Arabidopsis thaliana 
abi3-regulon. nucleic acids Res. 40 (2012) 8240-8254.
R
ohn
, h., a. h
artmann
, a. J
unker
, b.h. J
unker
 & F. S
chreiber
: FluxMap: 
a Vanted add-on for the visual exploration of flux distribu-
tions in biological networks. bMc Syst. biol. 6 (2012) 33.
R
ohn
,  h., a. J
unker
, a. h
artmann
, e. G
rafahrend
-b
elau
, h. t
reutler
, 
M. k
lapper
 
stück
, t. c
zauderna
, c. k
lukas
 & F. S
chreiber
: Vanted 
v2: a framework for systems biology applications. bMc Syst. 
biol. 6 (2012) 139.
S
chreiber
, F., c. c
olmsee
, t. c
zauderna
, e. G
rafahrend
-b
elau
, a. h
art
-
mann
, a. J
unker
, b.h. J
unker
, M. k
lapperstück
, u. S
cholz
 & S. W
eise
: 
Metacrop 2.0: managing and exploring information about 
crop plant metabolism. nucleic acids Res. 40 (2012) d1173-
d1177.
van
 i
ersel
, M.P., a.c. V
illéger
, t. c
zauderna
, S.e. b
oyd
, F.t. b
ergmann
, a. 
L
una
, e. d
emir
, a. S
orokin
, u. d
ogrusoz
, Y. M
atsuoka
, a. F
unaha
-
shi
, M.i. a
ladjem
, h. M
i
, S.L. M
oodie
, h. k
itano
, n. L
e
 n
ovère
 & F. 
S
chreiber
: Software support for SbGn maps: SbGn-ML and 
LibSbGn. bioinformatics 28 (2012) 2016-2021.
2013
a
sgari
, Y., a. S
alehzadeh
-Y
azdi
, F. S
chreiber
 & a. M
asoudi
-n
ejad
: con-
trollability in cancer metabolic networks according to drug 
targets as driver nodes. PLoS one 8 (2013) e79397.
b
aker
,  S.M., c.h. P
oskar
, F. S
chreiber
 & b.h. J
unker
: an improved 
constraint filtering technique for inferring hidden states 
and parameters of a biological model. bioinformatics 29 
(2013) 1052-1059.
b
üchel
, F., n. R
odriguez
, n. S
wainston
, c. W
rzodek
, t. c
zauderna
, R. 
k
eller
, F. M
ittag
, M. S
chubert
, M. G
lont
, M. G
olebiewski
, M. 
van
 
i
ersel
, S. k
eating
, M. R
all
, M. W
ybrow
, h. h
ermjakob
, M. h
ucka
, 
d.b. k
ell
, W. M
üller
, P. M
endes
, a. z
ell
, c. c
haouiya
, J. S
aez
-R
od
-
riguez
, F. S
chreiber
, c. L
aibe
, a. d
räger
 & n. L
e
 n
overe
: Path2Mo-
dels: large-scale generation of computational models from 
biochemical pathway maps. bMc Syst. biol. 7 (2013) 116.
c
olmsee
, c., t. c
zauderna
, e. G
rafahrend
-b
elau
, a. h
artmann
, M. L
an
-
ge
, M. M
ascher
, S. W
eise
, u. S
cholz
 & F. S
chreiber
: oPtiMaS-dW, 
Metacrop and Vanted: a case study for data integration, 
curation and visualisation in life sciences. Proc. odLS, Lect. 
notes inform. (Lni) P-220 (2013) 455.
c
zauderna
, t., M. W
ybrow
, k. M
arriott
 & F. S
chreiber
: conversion of 
keGG metabolic pathways to SbGn maps including auto-
matic layout. bMc bioinformatics 14 (2013) 250.
G
rafahrend
-b
elau
, e., a. J
unker
, a. e
schenröder
, J. M
üller
, F. S
chreiber
 
& b.h. J
unker
: Multiscale metabolic modeling: dynamic flux 
balance analysis on a whole plant scale. Plant Physiol. 163 
(2013) 637-647.
h
ofestädt
, R., b. k
ormeier
, M. L
ange
, F. S
chreiber
, b. S
ommer
 & S. W
eise
: 
editorial. J. integr. bioinform. 10 (2013) e226.
J
usufi
, i., a. k
erren
 & F. S
chreiber
: exploring biological data: map-
pings between ontology- and cluster-based representa-
tions. inform. Visual. 12 (2013) 291-307.
M
ehlhorn
, h. & F. S
chreiber
: transid – the flexible identifier map-
ping service. Proc. integrative bioinformatics (2013) 112-
121.
M
üller
, J., a. e
schenröder
, o. c
hristen
, b.h. J
unker
 & F. S
chreiber
: Pro-
net-cn model: a dynamic and hierarchical process network 
Publications
Peer Reviewed Papers
2012
c
olmsee
, c., M. M
ascher
, t. c
zauderna
, a. h
artmann
, u. S
chlüter
, n. 
z
ellerhoff
, J. S
chmitz
, a. b
räutigam
, t.R. P
ick
, P. a
lter
, M. G
ahrtz
, 
S. W
itt
, a.R. F
ernie
, F. b
örn
 
ke
, h. F
ahnenstich
, M. b
ucher
, t. 
d
resselhaus
, a.P. W
eber
, F. S
chreiber
, u. S
cholz
 & u. S
onnewald
: 
oPtiMaS-dW: a comprehensive transcriptomics, meta-
bolomics, ionomics, proteomics and phenomics data re-
source for maize. bMc Plant biol. 12 (2012) 245.
G
rässler
, J., d. k
oschützki
 & F. S
chreiber
: centiLib: comprehensive 
analysis and exploration of network centralities. bioinfor-
matics 28 (2012) 1178-1179.
h
artmann
, a., h. R
ohn
, k. P
ucknat
 & F. S
chreiber
: Petri nets in Van-
ted: Simulation of barley seed metabolism. Proc. 3
rd
 int. 
Workshop on biological Processes & Petri nets (bioPPn), 
ceuR Workshop Proc. 852 (2012) 20-28.
J
unker
, a. & h. b
äumlein
: Multifunctionality of the Lec1 transcrip-
tion factor during plant development. Plant Signal. behav. 
7 (2012) 1718-1720.
J
unker
, a., G. M
önke
, t. R
utten
, J. k
eilwagen
, M. S
eifert
, t.M. t
hi
, J.P. 
R
enou
, S. b
alzergue
, P. V
iehover
, u. h
ähnel
, J. L
udwig
-M
üller
, L. 
a
ltschmied
, u. c
onrad
, b. W
eisshaar
 & h. b
äumlein
: elongation-
related functions of LeaFY cotYLedon1 during the devel-
opment of Arabidopsis thaliana. Plant J. 71 (2012) 427-442.
J
unker
, a., h. R
ohn
, t. c
zauderna
, c. k
lukas
, a. h
artmann
 & F. S
chrei
-
ber
: creating interactive, web-based and data-enriched 
maps using the Systems biology Graphical notation. nature 
Protocols 7 (2012) 579-593.
J
unker
, a., h. R
ohn
 & F. S
chreiber
: Visual analysis of transcriptome 
data in the context of anatomical structures and biological 
networks. Front. Plant Sci. 3 (2012) 252.
J
unker
, a., a. S
orokin
, t. c
zauderna
, F. S
chreiber
 & a. M
azein
: Wiring dia-
grams in biology: towards the standardized representation of 
biological information. trends biotechnol. 30 (2012) 555-557.
J
usufi
, i., a. k
erren
 & F. S
chreiber
: Visualization of mappings be- 
t w een the gene ontology and cluster trees. Proc. SPIE 8294, 
Visualization and data analysis 2012 (2012) 82940n.
J
usufi
, i., c. k
lukas
, a. k
erren
 & F. S
chreiber
: Guiding the interactive 
exploration of metabolic pathway interconnections. infor-
mation Visualization 11 (2012) 136-150.
k
erren
, a. & F. S
chreiber
: towards the role of interaction in visual 
analytics. Proc. Winter Simulation conference – WSc (2012) 
420 (421-413).
L
otz
, k., F. S
chreiber
 & R. W
ünschiers
: nutrilyzer: a tool for deciphe-
ring atomic stoichiometry of differentially expressed para-
logous proteins. J. integr. bioinform. 9 (2012) 196.
M
asoudi
-n
ejad
,  a., F. S
chreiber
 & z.R. k
ashani
: building blocks of 
biological networks: a review on major network motif dis-
covery algorithms. iet Syst. biol. 6 (2012) 164-174.
M
ehlhorn
, h., M. L
ange
, u. S
cholz
 & F. S
chreiber
: idPredictor: pre-
dict database links in biomedical database. J. integr. bioin-
form. 9 (2012) e190.
M
önke
, G., M. S
eifert
, J. k
eilwagen
, M. M
ohr
, i. G
rosse
, u. h
ähnel
, a. J
un
-
ker
, b. W
eisshaar
, u. c
onrad
, h. b
äumlein
 & L. a
ltschmied
:  towards  

107
Other Papers
2012
M
ehlhorn
, h., M. L
ange
, u. S
cholz
 & F. S
chreiber
: idPredictor: Predict 
database links in biomedical database. Proc. 8
th
 int. Symp. 
integr. bioinform. (ib2012), zhejiang university, hangzhou, 
china, april 2
nd
 to 4
th
 2012 (2012) 135-148.
PhD and Diploma Theses
2012
a
rend
,  d.: konzeption und implementierung einer datenhal-
tungsinfrastruktur zur digitalen Langzeitarchivierung und 
dauerhaften zitierbarkeit biologischer Primärdaten am bei-
spiel von ”next-Generation-Sequencing“-daten. (diploma 
thesis) Martin-Luther-universität halle-Wittenberg, insti-
tut für informatik der naturwissenschaftlichen Fakultät iii, 
halle/S. (2012) 121 pp.
b
aker
, S.M.: a parameter estimation framework for kinetic mo-
dels of biological systems. (Phd thesis) Martin-Luther-uni-
versität halle-Wittenberg, institut für informatik der natur-
wissenschaftlichen Fakultät iii, halle/S. (2012) 150 pp.
G
rischau
, i.: die anwendung von magischen Linsen im kontext 
metabolischer netzwerke. (diploma thesis) otto-von-Gue-
ricke universität, Magdeburg (2012) 68 pp.
k
utz
, d.: editorerstellung für Vanted am beispiel von SbML. (di-
ploma thesis) Martin-Luther-universität halle-Wittenberg, 
institut für informatik der naturwissenschaftlichen Fakultät 
iii, halle/S. (2012) 114 pp.
M
irschel
,  S.: interactive visualization of complex structures in 
modular models for systems biology. (Phd thesis) Martin-
Luther-universität halle-Wittenberg, institut für informatik 
der naturwissenschaftlichen Fakultät iii, halle/S. (2012) 111 
pp.
P
ucknat
,  k.: erweiterung der Software Vanted zum editieren 
und Simulieren biologischer Petri-netze. (Master thesis) 
hochschule ostwestfalen-Lippe (2012) 77 pp.
R
ohn
,  h.: integrative Visualisierung multimodaler biologischer 
experimentaldaten. (Phd thesis) Martin-Luther-universität 
halle-Wittenberg, institut für informatik der naturwissen-
schaftlichen Fakultät iii, halle/S. (2012) 119 pp.
2013
bull, F.: Visualization of next-generation sequencing data using 
hilbert curves and their application to two species of Len-
tibulariaceae.  (diploma thesis) Martin-Luther-universität 
halle-Wittenberg, institut für informatik der naturwissen-
schaftlichen Fakultät iii, halle/S. (2013) 96 pp.
esch, M.: effizienzsteigerung des Life-Science iR-Systems Lai-
LaPS mittels Suchanfragenerweiterung. (Master thesis) 
Martin-Luther-universität halle-Wittenberg, institut für in-
formatik der naturwissenschaftlichen Fakultät iii, halle/S. 
(2013) 94 pp.
that couples photosynthesis, primary carbon metabolism 
and effects of leaf nitrogen status. Proc. 2012 ieee 4
th
 int. 
Symp. Plant Growth Modeling, Simulation, Visualization 
and applications – PMa (2013) 289-296.
V
ogt
, t., t. c
zauderna
 & F. S
chreiber
: translation of SbGn maps: Pro-
cess description to activity flow. bMc Syst. biol. 7 (2013) 115.
Books and Book Chapters
2012
G
rafahrend
-b
elau
,  e., b.h. J
unker
 & F. S
chreiber
: Plant metabolic 
path ways: database and pipeline for stoichiometric analysis. 
in: a
grawal
, G.k. & R. R
akwal
 (eds.): Seed development: omics 
technologies toward improvement of seed quality and crop 
yield. Springer, dordrecht, the netherlands (2012) 345-366.
J
unker
,  a. & b.h. J
unker
: Synthetic gene networks in plant sys-
tems. in: W
eber
,  w. & M. F
ussenegger
 (eds.): Synthetic gene 
networks: Methods and Protocols. Meth. Mol. biol. 813. hu-
mana Press, new York (2012) 343-358.
k
rach
, c., e. G
rafahrend
-b
elau
, h. P
oskar
, k. S
challau
, F. S
chreiber
 & 
b.h. J
unker
: using systems approaches to analyze metabolic 
networks involved in storage reserve synthesis in develop-
ing seeds. in: a
grawal
, G.k. & R. R
akwal
 (eds.): Seed develop-
ment: omics technologies toward improvement of seed 
quality and crop yield. Springer, dordrecht, the nether-
lands (2012) 387-406.
2013
b
achmaier
, c., u. b
randes
 & F. S
chreiber
: biological networks. in: t
a
-
massia
, R. (ed.): handbook of Graph drawing and Visualizati-
on. chapman & hall/cRc Press (2013) 621-652.
M
ehlhorn
,  h., M. L
ange
, u. S
cholz
 & F. S
chreiber
: extraction and 
prediction of biomedical database identifier using neural 
networks towards data network construction. in: o
rdóñez
 
de
 
P
ablos
, P., M.d. L
ytras
, R. t
ennyson
 & J.e. L
abra
 G
ayo
 (eds.): cases 
on open-Linked data and Semantic Web applications. iGi 
Global, (2013) 58-83.
M
ehlhorn
, h. & F. S
chreiber
: Small-world property of networks. in: 
d
ubitzky
, W., o. W
olkenhauer
, k.-h. c
ho
 & h. Y
okota
 (eds.): en-
cyclopedia of Systems biology. Springer Science+business 
Media, LLc (2013) 1957-1959.
S
chreiber
, F., R. h
ofestädt
, M. L
ange
, u. S
cholz
, t. c
zauderna
, R. S
chnee
 
& S. W
eise
 (eds.): Proceedings of the 9
th
 international Sym-
posium on integrative bioinformatics 2013, 18.-20.03.2013. 
Leibniz institute of Plant Genetics and crop Plant Research 
(iPk), Gatersleben (2013) 224 pp.
S
chreiber
,  F. & n. L
e
  n
ovère
: exchange formats for systems bio-
logy – SbGn. in: d
ubitzky
, W., o. W
olkenhauer
, k.-h. c
ho
 & h. 
Y
okota
 (eds.): encyclopedia of Systems biology. Springer 
Science+business Media, LLc (2013) 1893-1895.

Abteilung Molekulare Genetik/
Department of Molecular Genetics
108
G
ellner
, M.: evaluating the impact of genome quality on Rna-
seq analysis. (Master thesis) Martin-Luther-universität 
halle-Wittenberg, institut für informatik der naturwissen-
schaftlichen Fakultät iii, halle/S. (2013) 48 pp.
G
rafahrend
-b
elau
, e.: Rekonstruktion, analyse und Visualisierung 
pflanzenbiologischer Stoffwechselprozesse. (Phd thesis) 
Martin-Luther-universität halle-Wittenberg, institut für 
informatik der naturwissenschaftliche Fakultät iii, halle/S. 
(2013) 160 pp.
Grüneisen, b.: Graphbasierte Visualisierung medizinischer on-
tologie- & Gefäßdaten. (Master thesis) Martin-Luther-uni-
versität halle-Wittenberg, institut für informatik der natur-
wissenschaftlichen Fakultät iii, halle/S. (2013) 110 pp.
u
lpinnis
,  c.: evaluation von Fehlerkorrektur-algorithmen für 
Sequenzdaten in komplexen Pflanzengenomen. (bachelor 
thesis) Martin-Luther-universität halle-Wittenberg, insti-
tut für informatik der naturwissenschaftlichen Fakultät iii, 
halle/S. (2013) 119 pp.

109
the genes were extracted from Arabidopsis thaliana microar-
ray data, and a new motif was found that can be interpreted 
as an elongated auxin-responsive element. this result has been 
validated using an independent data set of auxin-responsive 
genes. the refined motif increased the auxin specificity by 
more than three orders of magnitude in genome-wide predic-
tions compared to the canonical auxin-responsive element.
(3) With help of reverse engineering we reconstructed gene regu-
latory networks in A. thaliana under varying conditions for tran-
scriptomic network comparison.  For that we used modern infor-
mation-theoretic approaches and integrated sequence analysis. 
(4) armed with a toolkit of modern probabilistic methods, we 
lately focused our research potential on the historical iPk Gene-
bank collection of cereals since 1946. the collection is one of 
the most important genetic recourses of cereals for research 
and breeding. it contains a very large collection of barley and 
wheat accessions (~ 50.000) which we analyzed first. 
to overcome technical and climatic biases we developed a new 
statistical approach for ranking the accessions. With help of this 
method we now can, for example, identify an optimal barley ac-
cession for any desired traits. based on such kind of analysis we 
defined groups of most contrasting accessions for an in depth 
analysis. this was done together with b. kilian from the iPk Gene-
bank group. We were able to prove in a breeding approach the 
usefulness of our methods on groups of contrasting barley ac-
cessions (see Fig. 33, p. 110). this would enable a more system-
atic and intelligent access to the plant genetic resources stored 
at the iPk Genebank for scientists and breeders world-wide.
Publications
Peer Reviewed Papers
2012
F
riedel
, S., b. u
sadel
, n. 
von
 W
irén
 & n. S
reenivasulu
: Reverse engi-
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