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Identification of Disease Genes Using Gene Expression and Protein–Protein Interaction Data

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Scalable Pattern Recognition Algorithms

Abstract

One of the most important and challenging problems in functional genomics is how to select the disease genes. In this chapter, a computational method is reported to identify disease genes, judiciously integrating the information of gene expression profiles and shortest path analysis of protein-protein interaction networks. While the gene expression profiles have been used to select differentially expressed genes as disease genes using mutual information-based maximum relevance-maximum significance framework, the functional protein association network has been used to study the mechanism of diseases. Extensive experimental study on colorectal cancer establishes the fact that the genes identified by the integrated method have more colorectal cancer genes than the genes identified from the gene expression profiles alone. All these results indicate that the integrated method is quite promising and may become a useful tool for identifying disease genes.

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References

  1. Althaus IW, Gonzales AJ, Chou JJ, Romero DL, Deibel MR, Chou KC, Kezdy FJ, Resnick L, Busso ME, So AG (1993) The quinoline U-78036 is a potent inhibitor of HIV-1 reverse transcriptase. J Biol Chem 268(20):14,875–14,880

    Google Scholar 

  2. Altshuler D, Daly MJ, Lander ES (2008) Genetic mapping in human disease. Science 322(5903):881–888

    Article  Google Scholar 

  3. Andraos J (2008) Kinetic plasticity and the determination of product ratios for kinetic schemes leading to multiple products without rate laws—new methods based on directed graphs. Can J Chem 86(4):342–357

    Article  Google Scholar 

  4. Barrenas F, Chavali S, Holme P, Mobini R, Benson M (2009) Network properties of complex human disease genes identified through genome-wide association studies. PLoS One 4(11):e8090

    Article  Google Scholar 

  5. Bogdanov P, Singh A (2010) Molecular function prediction using neighborhood features. IEEE/ACM Trans Comput Biol Bioinform 7(2):208–217

    Article  Google Scholar 

  6. Cai YD, Huang T, Feng KY, Hu L, Xie L (2010) A unified 35-gene signature for both subtype classification and survival prediction in diffuse large b-cell lymphomas. PLoS One 5(9):e12,726

    Article  Google Scholar 

  7. Chen J, Aronow B, Jegga A (2009) Disease candidate gene identification and prioritization using protein interaction networks. BMC Bioinform 10(1):73

    Article  Google Scholar 

  8. Chen L, Cai YD, Shi XH, Huang T (2010) Analysis of metabolic pathway using hybrid properties. PLoS One 5(6):e10,972

    Article  Google Scholar 

  9. Chou KC (1990) Applications of graph theory to enzyme kinetics and protein folding kinetics: steady and non-steady-state systems. Biophys Chem 35(1):1–24

    Article  Google Scholar 

  10. Chou KC (1993) Graphic rule for non-steady-state enzyme kinetics and protein folding kinetics. J Math Chem 12(1):97–108

    Article  Google Scholar 

  11. Chou KC (2010) Graphic rule for drug metabolism systems. Curr Drug Metab 11:369–378

    Article  Google Scholar 

  12. Chou KC, Forsen S (1980) Graphical rules for enzyme-catalysed rate laws. Biochem J 187:829–835

    Google Scholar 

  13. Chou KC, Kezdy FJ, Reusser F (1994) Kinetics of processive nucleic acid polymerases and nucleases. Anal Biochem 221(2):217–230

    Article  Google Scholar 

  14. Dermitzakis ET (2008) From gene expression to disease risk. Nat Genet 40:492–493

    Article  Google Scholar 

  15. Dijkstra EW (1959) A note on two problems in connexion with graphs. Numer Math 1(1):269–271

    Article  MATH  MathSciNet  Google Scholar 

  16. Ding C, Peng H (2003) Minimum redundancy feature selection from microarray gene expression data. In: Proceedings of the international conference on computational systems, bioinformatics, pp. 523–528

    Google Scholar 

  17. Ding C, Peng H (2005) Minimum redundancy feature selection from microarray gene expression data. J Bioinform Comput Biol 3(2):185–205

    Article  MathSciNet  Google Scholar 

  18. Duda RO, Hart PE, Stork DG (1999) Pattern classification and scene analysis. Wiley, New York

    Google Scholar 

  19. Goh KI, Cusick ME, Valle D, Childs B, Vidal M, Barabsi AL (2007) The human disease network. Proc Natl Acad Sci 104(21):8685–8690

    Article  Google Scholar 

  20. Hinoue T, Weisenberger DJ, Lange CP, Shen H, Byun HM, Van Den Berg D, Malik S, Pan F, Noushmehr H, van Dijk CM, Tollenaar RAEM, Laird PW (2012) Genome-scale analysis of aberrant DNA methylation in colorectal cancer. Genome Res 22(2):271–282

    Article  Google Scholar 

  21. Huang T, Cui W, Hu L, Feng K, Li YX, Cai YD (2009) Prediction of pharmacological and xenobiotic responses to drugs based on time course gene expression profiles. PLoS One 4(12):e8126

    Article  Google Scholar 

  22. Huang T, Cai YD, Chen L, Hu LL, Kong XY, Li YX, Chou KC (2010) Selection of reprogramming factors of induced pluripotent stem cells based on the protein interaction network and functional profiles. PLoS One 5(9):e12,726

    Article  Google Scholar 

  23. Huang T, Shi XH, Wang P, He Z, Feng KY, Hu L, Kong X, Li YX, Cai YD, Chou KC (2010) Analysis and prediction of the metabolic stability of proteins based on their sequential features, subcellular locations and interaction networks. PLoS One 5(6):e10,972

    Google Scholar 

  24. Huang T, Chen L, Cai YD, Chou KC (2011) Classification and analysis of regulatory pathways using graph property, biochemical and physicochemical property, and functional property. PLoS One 6(9):e25,297

    Google Scholar 

  25. Huret JL, Dessen P, Bernheim A (2003) Atlas of genetics and cytogenetics in oncology and haematology, year 2003. Nucleic Acids Res 31(1):272–274

    Article  Google Scholar 

  26. Jia P, Zheng S, Long J, Zheng W, Zhao Z (2011) dmGWAS: dense module searching for genome-wide association studies in protein–protein interaction networks. Bioinformatics 27(1):95–102

    Article  Google Scholar 

  27. Karaoz U, Murali TM, Letovsky S, Zheng Y, Ding C, Cantor CR, Kasif S (2004) Whole-genome annotation by using evidence integration in functional-linkage networks. Proc Natl Acad Sci 101(9):2888–2893

    Article  Google Scholar 

  28. Karni S, Soreq H, Sharan R (2009) A network-based method for predicting disease-causing genes. J Comput Biol 16(2):181–189

    Article  Google Scholar 

  29. Keshava Prasad TS, Goel R, Kandasamy K, Keerthikumar S, Kumar S, Mathivanan S, Telikicherla D, Raju R, Shafreen B, Venugopal A, Balakrishnan L, Marimuthu A, Banerjee S, Somanathan DS, Sebastian A, Rani S, Ray S, Harrys Kishore CJ, Kanth S, Ahmed M, Kashyap MK, Mohmood R, Ramachandra YL, Krishna V, Rahiman BA, Mohan S, Ranganathan P, Ramabadran S, Chaerkady R, Pandey A (2009) Human protein reference database-2009 update. Nucleic Acids Res 37(suppl 1):D767–D772

    Google Scholar 

  30. Kohler S, Bauer S, Horn D, Robinson PN (2008) Walking the interactome for prioritization of candidate disease genes. Am J Hum Genet 82(4):949–958

    Article  Google Scholar 

  31. Kourmpetis YAI, van Dijk ADJ, Bink MCAM, van Ham RCHJ, ter Braak CJF (2010) Bayesian Markov random field analysis for protein function prediction based on network data. PLoS One 5(2):e9293

    Article  Google Scholar 

  32. Letovsky S, Kasif S (2003) Predicting protein function from protein/protein interaction data: a probabilistic approach. Bioinformatics 19(suppl 1):i197–i204

    Article  Google Scholar 

  33. Li BQ, Huang T, Liu L, Cai YD, Chou KC (2012) Identification of colorectal cancer related genes with mRMR and shortest path in protein–protein interaction network. PLoS one 7(4):e33,393

    Google Scholar 

  34. Li Y, Li J (2012) Disease gene identification by random walk on multigraphs merging heterogeneous genomic and phenotype data. BMC Genomics 13(Suppl 7):S27

    Article  Google Scholar 

  35. Maji P, Paul S (2011) Rough set based maximum relevance-maximum significance criterion and gene selection from microarray data. Int J Approximate Reasoning 52(3):408–426

    Article  Google Scholar 

  36. Meltzer PS (2001) Spotting the target: microarrays for disease gene discovery. Curr Opin Genet Dev. 11(3):258–263

    Article  Google Scholar 

  37. Mohammadi A, Saraee M, Salehi M (2011) Identification of disease-causing genes using microarray data mining and gene ontology. BMC Med Genomics 4(1):12

    Article  Google Scholar 

  38. Nagaraj S, Reverter A (2011) A boolean-based systems biology approach to predict novel genes associated with cancer: application to colorectal cancer. BMC Syst Biol 5(1):35

    Article  Google Scholar 

  39. Navlakha S, Kingsford C (2010) The power of protein interaction networks for associating genes with diseases. Bioinformatics 26(8):1057–1063

    Article  Google Scholar 

  40. Ng KL, Ciou JS, Huang CH (2010) Prediction of protein functions based on function–function correlation relations. Comput Biol Med 40(3):300–305

    Article  Google Scholar 

  41. Nitsch D, Tranchevent LC, Thienpont B, Thorrez L, Van Esch H, Devriendt K, Moreau Y (2009) Network analysis of differential expression for the identification of disease-causing genes. PLoS One 4(5):e5526

    Article  Google Scholar 

  42. Novershtern N, Itzhaki Z, Manor O, Friedman N, Kaminski N (2008) A functional and regulatory map of asthma. Am J Resp Cell Mol Biol 38(3):324–336

    Article  Google Scholar 

  43. Oti M, Snel B, Huynen MA, Brunner HG (2006) Predicting disease genes using protein–protein interactions. J Med Genet 43(8):691–698

    Article  Google Scholar 

  44. Paul S, Maji P (2013) Gene ontology based quantitative index to select functionally diverse genes. Int J Mach Learn Cybern. doi:10.1007/s13042-012-0133-5.

  45. Quenouille MH (1949) Approximate tests of correlation in time-series. J Roy Stat Soc Ser B (Methodol) 11(1):68–84

    Google Scholar 

  46. Ruan X, Wang J, Li H, Perozzi RE, Perozzi EF (2008) The use of logic relationships to model colon cancer gene expression networks with mRNA microarray data. J Biomed Inform 41(4):530–543

    Article  Google Scholar 

  47. Sabates-Bellver J, Van der Flier LG, de Palo M, Cattaneo E, Maake C, Rehrauer H, Laczko E, Kurowski MA, Bujnicki JM, Menigatti M, Luz J, Ranalli TV, Gomes V, Pastorelli A, Faggiani R, Anti M, Jiricny J, Clevers H, Marra G (2007) Transcriptome profile of human colorectal adenomas. Mol Cancer Res 5(12):1263–1275

    Article  Google Scholar 

  48. Sharan R, Ulitsky I, Shamir R (2007) Network-based prediction of protein function. Mol Syst Biol 3(88):1–13

    Google Scholar 

  49. Szklarczyk D, Franceschini A, Kuhn M, Simonovic M, Roth A, Minguez P, Doerks T, Stark M, Muller J, Bork P, Jensen LJ, von Mering C (2011) The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res 39(suppl 1):D561–D568

    Article  Google Scholar 

  50. Vajda I (1989) Theory of statistical inference and information. Kluwer Academic, Dordrecht

    MATH  Google Scholar 

  51. Wu C, Zhu J, Zhang X (2012) Integrating gene expression and protein–protein interaction network to prioritize cancer-associated genes. BMC Bioinform 13(1):182

    Article  MathSciNet  Google Scholar 

  52. Zhao J, Jiang P, Zhang W (2010) Molecular networks for the study of TCM pharmacology. Briefings Bioinform 11(4):417–430

    Article  Google Scholar 

  53. Zhao J, Yang TH, Huang Y, Holme P (2011) Ranking candidate disease Genes from gene expression and protein interaction: a Katz-centrality based approach. PLoS One 6(9):e24,306

    Google Scholar 

  54. Zhou GP (2011) The disposition of the LZCC protein residues in Wenxiang diagram provides new insights into the protein–protein interaction mechanism. J Theor Biol 284(1):142–148

    Article  Google Scholar 

  55. Zhou GP, Deng MH (1984) An extension of Chou’s graphic rules for deriving enzyme kinetic equations to systems involving parallel reaction pathways. Biochem J 222:169–176

    Google Scholar 

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Correspondence to Pradipta Maji .

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Maji, P., Paul, S. (2014). Identification of Disease Genes Using Gene Expression and Protein–Protein Interaction Data. In: Scalable Pattern Recognition Algorithms. Springer, Cham. https://doi.org/10.1007/978-3-319-05630-2_6

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  • DOI: https://doi.org/10.1007/978-3-319-05630-2_6

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