Abstract
The accurate diagnosis of complex disorders is the prerequisite of appropriate and effective treatment. Ideally, the diagnostic process should include the evaluation of molecular and clinic tests alongside medical observations; these clinical observations and laboratory outcomes are usually integrated by an expert physician or one prevails and the other is used for mere confirmation. In clinical bioinformatics, complex datasets are investigated with the aim to improve the clinical management of diseases. The integration of data from disparate data sources is urgently needed and is the prerequisite in the implementation of network medicine which views disease relevant properties as networks and tries to untangle the information content in these networks. Here we developed a graph theoretical framework for combining and untangling the relationships of physiological and molecular data. We then applied the methodology to determine disease related abnormalities of a molecular network derived from serum of patients with schizophrenia and affective disorder. The universality of the concept is demonstrated by an integration of the metabolic data with a standard laboratory test of glucose measurements. The generation of compound networks allows the integrated analysis of disease relevant information and the detection of robust patterns ultimately facilitating the description of complex disorders. This approach could lead to an automatized methodology for improving disease classification and diagnosis.
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References
Ronald, J.A.: Trent: Clinical Bioinformatics: Preliminary Entry 2008 (Methods in Molecular Medicine). Humana Press Inc., U.S. (2007)
Jones, N.C., Pevzner, P.A.: An Introduction to Bioinformatics Algorithms (Computational Molecular Biology). The MIT Press, Cambridge (2004)
Durbin, R., Eddy, S.R., Krogh, A., Mitchison, G.: Biological Sequence Analysis: Probabilistic Models of Proteins and Nucleic Acids. Cambridge University Press, Cambridge (1999)
Gusfield, D.: Algorithms on Strings, Trees and Sequences: Computer Science and Computational Biology. Cambridge University Press, Cambridge (1997)
Gibas, C., Jambeck, P.: Developing Bioinformatics Computer Skills, 1st edn. OāReilly Media, Inc. (2001)
Nagl, S.: Cancer Bioinformatics: From Therapy Design to Treatment. John Wiley & Sons, Chichester (2006)
Alon, U.: An Introduction to Systems Biology: Design Principles of Biological Circuits. Crc Mathematical and Computational Biology. Chapman & Hall, Boca Raton (2006)
Wagner, A.: Robustness and Evolvability in Living Systems (Princeton Studies in Complexity). Princeton University Press, Princeton (2005)
Palsson, B.O.: Systems Biology: Properties of Reconstructed Networks. Cambridge University Press, Cambridge (2006)
Wilkinson, D.J.: Stochastic Modelling for Systems Biology (Mathematical and Computational Biology). Chapman & Hall/CRC, Boca Raton (2006)
Pastor-Satorras, R., Vespignani, A.: Epidemic Spreading in Scale-Free Networks. Phys. Rev. Lett.Ā 86, 3200 (2001)
Gross, T., Dommar DāLima, C.J., Blasius, B.: Epidemic dynamics on an adaptive network. Phys. Rev. Lett.Ā 96, 208701 (2006)
Boccaletti, S., Latora, V., Moreno, Y., Chavez, M., Hwang, D.-U.: Complex Networks: Structure and Dynamics. Physics ReportsĀ 424, 175 (2006)
Dorogovtsev, S.N., Mendes, J.F.F., Samukhin, A.N.: Structure of Growing Networks with Preferential Linking. Phys. Rev. LettĀ 85, 4633 (2000)
Colizza, V., Barrat, A., BarthĆ©lemy, M., Vespignani, A.: Prediction and predictability of global epidemics: the role of the airline transportation network. Proc. Natl. Acad. Sci. U.S.A.Ā 103, 2015 (2006)
Newman, M.E., Girvan, M.: Finding and evaluating community structure in networks. Phys Rev. E Stat. Nonlin. Soft Matter Phys.Ā 69, 26113 (2004)
Bower, J.M., Bolouri, H. (eds.): Computational Modeling of Genetic and Biochemical Networks. MIT Press, Cambridge (2001)
Fall, C.P., Marland, E.S., Wagner, J.M., Tyson, J.J. (eds.): Computational Cell Biology. Springer, Heidelberg (2002)
Enright, A.J., Van Dongen, S., Ouzounis, C.A.: An efficient algorithm for large-scale detection of protein families. Nucleic Acids ResearchĀ 30(7), 1575ā1584 (2002)
van Dongen, S.: Graph Clustering by Flow Simulation. PhD thesis, University of Utrecht (May 2000)
Watts, D.J., Strogatz, S.H.: Collective dynamics of āsmall-worldā networks. NatureĀ 393, 440ā442 (1998)
Albert, R., Barabasi, A.: Statistical mechanics of complex networks. Rev. Mod. Phys.Ā 74, 47 (2002)
Hatzimanikatis, V., Li, C., Ionita, J.A., Broadbelt, L.J.: Metabolic networks: enzyme function and metabolite structure. Curr. Opin. Struct. Biol.Ā 14, 300ā306 (2004)
Forster, J., Famili, I., Fu, P., Palsson, B.O., Nielsen, J.: Genome-scale reconstruction of the Saccharomyces cerevisiae metabolic network. Genome Res.Ā 13, 244ā253 (2003)
Mishra, N.S., Tuteja, R., Tuteja, N.: Signaling through MAP kinase networks in plants. Arch Biochem. Biophys.Ā 452, 55ā68 (2006)
Rousseau, F., Schymkowitz, J.: A systems biology perspective on protein structural dynamics and signal transduction. Curr. Opin. Struct. Biol.Ā 15, 23ā30 (2005)
Galperin, M.Y.: Bacterial signal transduction network in a genomic perspective. Environ. Microbiol.Ā 6, 552ā567 (2004)
Monge, R.A., Roman, E., Nombela, C., Pla, J.: The MAP kinase signal transduction network in Candida albicans. MicrobiologyĀ 152, 905ā912 (2006)
Herrgard, M.J., Covert, M.W., Palsson, B.O.: Reconstruction of microbial transcriptional regulatory networks. Curr. Opin. Biotechnol.Ā 15, 70ā77 (2004)
Kanehisa, M.: Post-genome Informatics. Oxford University Press, Oxford (2000)
Barabasi, A.L., Oltvai, Z.: Network biology: understanding the cellās functional organization. Nat. Rev. Genet.Ā 5, 101ā113 (2004)
Zhang, Z., Luo, Z.W., Kishino, H., Kearsey, M.J.: Divergence Pattern of Duplicate Genes in Protein-Protein Interactions Follows the Power Law. Mol. Biol. Evol.Ā 22, 501ā505 (2005)
Wagner, A.: The yeast protein interaction network evolves rapidly and contains few redundant duplicate genes. Mol. Biol. Evol.Ā 18, 1283ā1292 (2001)
Wagner, A., Fell, D.A.: The small world inside large metabolic networks. Proc. R. Soc. London Ser. BĀ 268, 1803 (2001)
Guimera, R., Sales-Pardo, M., Amaral, L.A.: Modularity from fluctuations in random graphs and complex networks. Phys. Rev. E Stat. Nonlin. Soft Matter Phys.Ā 70(2 Pt 2), 25101 (2004)
Fortunato, S., Barthelemy, M.: Resolution limit in community detection. Proc. Natl. Acad. Sci. U S AĀ 104, 36ā41 (2007)
Gfeller, D., Chappelier, J.C., De Los Rios, P.: Finding instabilities in the community structure of complex networks. Phys. Rev. E Stat. Nonlin. Soft Matter PhysĀ 75, 56135 (2005)
Caretta-Cartozo, C., De Los Rios, P., Piazza, F., LiĆ³, P.: Bottleneck genes and community structure in the cell cycle network of S. pombe. PLoS Comput. Biol.Ā 3(6), e103
Tetko, I.V., Facius, A., Ruepp, A., Mewes, H.W.: Super paramagnetic clustering of protein sequences. BMC BioinformaticsĀ 6, 82 (2005)
Uetz, P., Giot, L., Cagney, G., Mansfield, T.A., Judson, R.S., Knight, J.R., Lockshon, D., Narayan, V., Srinivasan, M., Pochart, P., Qureshi-Emili, A., Li, Y., Godwin, B., Conover, D., Kalbfleisch, T., Vijayadamodar, G., Yang, M., Johnston, M., Fields, S., Rothberg, J.M.: A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae. NatureĀ 403, 623ā627 (2000)
Goh, K.I., Oh, E., Jeong, H., Kahng, B., Kim, D.: Classification of scale-free networks. Proc. Natl. Acad. Sci. U S AĀ 99, 12583ā12588 (2002)
Li, S., Armstrong, C.M., Bertin, N., Ge, H., Milstein, S., Boxem., M., Vidalain, P.-O., Han, J.-D.J., Chesneau, A., Hao, T., Goldberg, D.S., Li, N., Martinez, M., Rual, J.-F., Lamesch, P., Xu, L., Tewari, M., Wong, S.L., Zhang, L.V., Berritz, G.F., Jacotot, L., Vaglio, P., Reboul, J., Hirozane-Kishikawa, T., Li, Q., Gabel, H.W., Elewa, A., Baumgartner, B., Rose, D.J., Yu, H., Bosak, S., Sequerra, R., Fraser, A., Mange, S.E., Saxton, W.M., Strome, S., van den Heuvel, S., Piano, F., Vandenhaute, J., Sardet, C., Gerstein, M., Doucette-Stamm, L., Gunsalus, K.C., Harper, J.W., Cusick, M.E., Roth, F.P., Hill, D.E., Vidal, M.: A map of the interactome network of the metazoan C. elegans. ScienceĀ 303, 540ā543 (2004)
Koonin, E.V., Wolf, Y.I., Karev, G.P.: The structure of the protein universe and genome evolution. NatureĀ 420, 218ā223 (2002)
Barabasi, A.L.: Network medicineāfrom obesity to the ādiseasome. N Engl. J. Med.Ā 357(4), 404ā407 (2007)
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Schwarz, E., Leweke, F.M., Bahn, S., LiĆ², P. (2008). Combining Molecular and Physiological Data of Complex Disorders. In: Elloumi, M., KĆ¼ng, J., Linial, M., Murphy, R.F., Schneider, K., Toma, C. (eds) Bioinformatics Research and Development. BIRD 2008. Communications in Computer and Information Science, vol 13. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-70600-7_27
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DOI: https://doi.org/10.1007/978-3-540-70600-7_27
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