Systems Biology (Methods in Molecular Biology)

with critical interactions that might be critical for specific phenotype.
The network-based approach with the aim of getting insights into
the mechanisms underlying processes dysregulated in diseases is
almost the “state of the art” now. For example, Matsuoka et al.
created a large detailed pathway map of influenza A virus replication
cycle [20]. The map is annotated with around 500 scientific articles
and includes information from already developed influenza maps and
incorporate pathways information from KEGG, PANTHER, and
Reactom databases. This study was intended to develop a broader
picture of functional mechanism of influenza A virus and its asso-
ciated host response. Further, the map was used for in silicoanalysis
to identify several critical targets for influenza A virus life cycle.
Calzone et al. constructed a comprehensive map of RB/E2F path-
way interactions in the regulation of cell cycle [23]. It contains more
detailed and systematic information than any general purpose data-
bases about the study and serves as a knowledge-base. They identi-
fied different structural modules in the map based on clusters of
relevant cycles in the reaction graph.

Standard represetation in

CellDesigner/VANTED

Literature

Gene ́A ́

activates

gene ́B ́

Domain knowledge

Methods for

automatic map

construction

+

Pathway

search

Databases

IntAct

HPRD

DIP

BioCyc

KEGG

miRTarBase

Network construction

X

Y

X

Y

ATP ADP

XY

S1 P1

represetationin

igner/VANTED

Methodsfor

automaticmap

construction

Pathway

search

X

Y

ADP

Y

P 1

Fig. 3Scheme for biochemical network construction. More detailed and highly
focused networks, centered around a particular disease or process, can be
constructed by expert domain knowledge (functional and structural information),
diligent manual search of published literature, and publically available databases
(e.g., HPRD, IntAct, DIP, BioCyc, KEGG, REACTOME, and miRTarBase)

Integrative Workflow for Predicting Disease Signatures 253