Systems Biology (Methods in Molecular Biology)

(Tina Sui) #1
We promote here an integrative workflow that combines net-
work structural and dynamical analysis with high-throughput –omics
data and other biomedical information to gain mechanistic insights
into the causes of differentiated expression patterns from normal to
disease state. To this end, we constructed the transcription factor-
miRNA regulatory network to understand the mechanisms of meta-
static phenotype in prostate cancer.
To further substantiate the analysis, one can use the dynamical
systems theory to construct a mathematical model using suitable
modeling formalism. The dynamical analysis, for example in silico
stimulus response or perturbation analyses, of biochemical net-
works helps in understanding the functioning of a system and
provides an opportunity to formulate new hypotheses about the
effect of specific internal or external perturbations in a system. In
the systems biology approach, the iterative cycle of data-driven
modeling and model-driven experimentations refine the formu-
lated hypotheses until they are validated, which help to understand
complex mechanisms in certain biological traits.

References



  1. Barabasi A-L, Gulbahce N, Loscalzo J (2011)
    Network medicine: a network-based approach
    to human disease. Nat Rev Genetics
    12:56–68

  2. Chuang H-Y, Lee E, Liu Y-T et al (2007)
    Network-based classification of breast cancer
    metastasis. Mol Syst Biol 3:140

  3. Csermely P, Korcsma ́ros T, Kiss HJM et al
    (2013) Structure and dynamics of molecular
    networks: a novel paradigm of drug discovery:
    a comprehensive review. Pharmacol Ther
    138:333–408

  4. Alon U (2007) Network motifs: theory and
    experimental approaches. Nat Rev Genet
    8:450–461

  5. Kitano H (2007) A robustness-based
    approach to systems-oriented drug design.
    Nat Rev Drug Discov 6:202–210

  6. Wolkenhauer O (2014) Why model? Front
    Physiol 5:21

  7. Le Nove`re N (2015) Quantitative and logic
    modelling of molecular and gene networks.
    Nat Rev Genet 16:146–158

  8. Voit EO (2009) A {systems-theoretical}
    framework for health and disease. Math Biosci
    217:11–18

  9. Sadeghi M, Ranjbar B, Ganjalikhany MR et al
    (2016) MicroRNA and transcription factor
    gene regulatory network analysis reveals key
    regulatory elements associated with prostate
    cancer progression. PLoS One 11:e0168760
    10. Ideker T, Galitski T, Hood L (2001) A
    new approach to decoding life: systems biol-
    ogy. Annu Rev Genomics Hum Genet
    2:343–372
    11. Kitano H (2002) Systems biology: a brief
    overview. Science (New York, NY)
    295:1662–1664
    12. Funahashi A, Morohashi M, Kitano H et al
    (2003) CellDesigner: a process diagram edi-
    tor for gene-regulatory and biochemical net-
    works. Biosilico 1:159–162
    13. Shannon P, Markiel A, Ozier O et al (2003)
    Cytoscape: a software environment for
    integrated models of biomolecular interaction
    networks. Genome Res 13:2498–2504
    14. Junker BH, Klukas C, Schreiber F (2006)
    VANTED: a system for advanced data analysis
    and visualization in the context of biological
    networks. BMC Bioinformatics 7:109
    15. Ashyraliyev M, Fomekong-Nanfack Y, Kaan-
    dorp JA et al (2009) Systems biology: param-
    eter estimation for biochemical models. FEBS
    J 276(4):886–902
    16. Wittig U, Kania R, Golebiewski M et al
    (2012) SABIO-RK—database for biochemi-
    cal reaction kinetics. Nucleic Acids Res 40:
    D790–D796
    17. Li C, Donizelli M, Rodriguez N et al (2010)
    BioModels database: an enhanced, curated
    and annotated resource for published quanti-
    tative kinetic models. BMC Syst Biol 4:92


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