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BioMed Research International
Volume 2017, Article ID 5741948, 15 pages
https://doi.org/10.1155/2017/5741948
Research Article

Identification of Candidate Genes Related to Inflammatory Bowel Disease Using Minimum Redundancy Maximum Relevance, Incremental Feature Selection, and the Shortest-Path Approach

1Department of Science & Technology, Binzhou Medical University Hospital, Binzhou 256603, Shandong, China
2Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
3School of Life Sciences, Shanghai University, Shanghai 200444, China

Correspondence should be addressed to Fei Yuan; moc.kooltuo@frykwahwons

Received 26 August 2016; Accepted 11 January 2017; Published 14 February 2017

Academic Editor: Mikihiro Fujiya

Copyright © 2017 Fei Yuan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. D. J. Mulder, A. J. Noble, C. J. Justinich, and J. M. Duffin, “A tale of two diseases: the history of inflammatory bowel disease,” Journal of Crohn's and Colitis, vol. 8, no. 5, pp. 341–348, 2014. View at Publisher · View at Google Scholar · View at Scopus
  2. G. Barbara, C. Cremon, and V. Stanghellini, “Inflammatory bowel disease and irritable bowel syndrome: similarities and differences,” Current Opinion in Gastroenterology, vol. 30, no. 4, pp. 352–358, 2014. View at Publisher · View at Google Scholar · View at Scopus
  3. G. Bassotti, E. Antonelli, V. Villanacci, M. Salemme, M. Coppola, and V. Annese, “Gastrointestinal motility disorders in inflammatory bowel diseases,” World Journal of Gastroenterology, vol. 20, no. 1, pp. 37–44, 2014. View at Publisher · View at Google Scholar · View at Scopus
  4. M. Zippi, C. Corrado, R. Pica et al., “Extraintestinal manifestations in a large series of Italian inflammatory bowel disease patients,” World Journal of Gastroenterology, vol. 20, no. 46, pp. 17463–17467, 2014. View at Publisher · View at Google Scholar · View at Scopus
  5. A. Marineata, E. Rezus, C. Mihai, and C. C. Prelipcean, “Extra intestinal manifestations and complications in inflammatory bowel disease,” Revista Medico-Chirurgicala a Societatii de Medici si Naturalisti din Iasi, vol. 118, no. 2, pp. 279–288, 2014. View at Google Scholar
  6. P. L. Lakatos, L. Lakatos, L. S. Kiss, L. Peyrin-Biroulet, A. Schoepfer, and S. Vavricka, “Treatment of extraintestinal manifestations in inflammatory bowel disease,” Digestion, vol. 86, no. 1, pp. 28–35, 2012. View at Publisher · View at Google Scholar · View at Scopus
  7. S. Singh, I. J. Kullo, D. S. Pardi, and E. V. Loftus Jr., “Epidemiology, risk factors and management of cardiovascular diseases in IBD,” Nature Reviews Gastroenterology & Hepatology, vol. 12, no. 1, pp. 26–35, 2015. View at Publisher · View at Google Scholar · View at Scopus
  8. J. Ruel, D. Ruane, S. Mehandru, C. Gower-Rousseau, and J.-F. Colombel, “IBD across the age spectrum—is it the same disease?” Nature Reviews Gastroenterology and Hepatology, vol. 11, no. 2, pp. 88–98, 2014. View at Publisher · View at Google Scholar · View at Scopus
  9. E. Jaźwińska-Tarnawska, I. Jęśkowiak, E. Waszczuk et al., “Genetic polymorphism of ABCB1 gene (C3435T) in patients with inflammatory bowel diseases. Is there any gender dependency?” Pharmacological Reports, vol. 67, no. 2, pp. 294–298, 2015. View at Publisher · View at Google Scholar · View at Scopus
  10. C. Jakobsen, I. Cleynen, P. S. Andersen et al., “Genetic susceptibility and genotype-phenotype association in 588 Danish children with inflammatory bowel disease,” Journal of Crohn's & Colitis, vol. 8, no. 7, pp. 678–685, 2014. View at Publisher · View at Google Scholar · View at Scopus
  11. G. C. Nguyen, C. A. Chong, and R. Y. Chong, “National estimates of the burden of inflammatory bowel disease among racial and ethnic groups in the United States,” Journal of Crohn's and Colitis, vol. 8, no. 4, pp. 288–295, 2014. View at Publisher · View at Google Scholar · View at Scopus
  12. Y. Zhang and Y. Y. Li, “Inflammatory bowel disease: pathogenesis,” World Journal of Gastroenterology, vol. 20, no. 1, pp. 91–99, 2014. View at Publisher · View at Google Scholar
  13. P. Flanagan, B. J. Campbell, and J. M. Rhodes, “Bacteria in the pathogenesis of inflammatory bowel disease,” Biochemical Society Transactions, vol. 39, no. 4, pp. 1067–1072, 2011. View at Publisher · View at Google Scholar
  14. C. W. Lees, J. C. Barrett, M. Parkes, and J. Satsangi, “New IBD genetics: common pathways with other diseases,” Gut, vol. 60, no. 12, pp. 1739–1753, 2011. View at Publisher · View at Google Scholar · View at Scopus
  15. J. Glas, J. Seiderer, J. Wagner et al., “Analysis of IL12B gene variants in inflammatory bowel disease,” PLOS ONE, vol. 7, no. 3, Article ID e34349, 2012. View at Publisher · View at Google Scholar
  16. G. John, J. P. Hegarty, W. Yu et al., “NKX2-3 variant rs11190140 is associated with IBD and alters binding of NFAT,” Molecular Genetics and Metabolism, vol. 104, no. 1-2, pp. 174–179, 2011. View at Publisher · View at Google Scholar · View at Scopus
  17. K. L. VanDussen, T. C. Liu, D. Li et al., “Genetic variants synthesize to produce paneth cell phenotypes that define subtypes of Crohn's disease,” Gastroenterology, vol. 146, no. 1, pp. 200–209, 2014. View at Publisher · View at Google Scholar
  18. K. Kabashima, T. Saji, T. Murata et al., “The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut,” Journal of Clinical Investigation, vol. 109, no. 7, pp. 883–893, 2002. View at Publisher · View at Google Scholar
  19. G. Patman, “Crohn's disease: suppression of p21Rac1 signalling contributes to skip-lesion phenotype in Crohn's disease,” Nature Reviews Gastroenterology & Hepatology, vol. 11, no. 6, article 332, 2014. View at Publisher · View at Google Scholar · View at Scopus
  20. J. J. Rumessen, “Ultrastructure of interstitial cells of Cajal at the colonic submuscular border in patients with ulcerative colitis,” Gastroenterology, vol. 111, no. 6, pp. 1447–1455, 1996. View at Publisher · View at Google Scholar · View at Scopus
  21. J. Hampe, A. Franke, P. Rosenstiel et al., “A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1,” Nature Genetics, vol. 39, no. 2, pp. 207–211, 2007. View at Publisher · View at Google Scholar · View at Scopus
  22. M. Parkes, J. C. Barrett, N. J. Prescott et al., “Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility,” Nature Genetics, vol. 39, no. 7, pp. 830–832, 2007. View at Publisher · View at Google Scholar
  23. T. Hisamatsu, M. Suzuki, H.-C. Reinecker, W. J. Nadeau, B. A. McCormick, and D. K. Podolsky, “CARD15/NOD2 functions as an antibacterial factor in human intestinal epithelial cells,” Gastroenterology, vol. 124, no. 4, pp. 993–1000, 2003. View at Publisher · View at Google Scholar · View at Scopus
  24. E. Leung, J. Hong, A. G. Fraser, T. R. Merriman, P. Vishnu, and G. W. Krissansen, “Polymorphisms in the organic cation transporter genes SLC22A4 and SLC22A5 and Crohn's disease in a New Zealand Caucasian cohort,” Immunology and Cell Biology, vol. 84, no. 2, pp. 233–236, 2006. View at Publisher · View at Google Scholar · View at Scopus
  25. D. F. McCole, “Regulation of epithelial barrier function by the inflammatory bowel disease candidate gene, PTPN2,” Annals of the New York Academy of Sciences, vol. 1257, no. 1, pp. 108–114, 2012. View at Publisher · View at Google Scholar · View at Scopus
  26. H. Peng, F. Long, and C. Ding, “Feature selection based on mutual information: criteria of max-dependency, max-relevance, and min-redundancy,” IEEE Transactions on Pattern Analysis and Machine Intelligence, vol. 27, no. 8, pp. 1226–1238, 2005. View at Publisher · View at Google Scholar · View at Scopus
  27. J. Platt, Fast Training of Support Vector Machines Using Sequential Minimal Optimization, MIT Press, Cambridge, Mass, USA, 1998.
  28. S. S. Keerthi, S. K. Shevade, C. Bhattacharyya, and K. R. K. Murthy, “Improvements to Platt's SMO algorithm for SVM classifier design,” Neural Computation, vol. 13, no. 3, pp. 637–649, 2001. View at Publisher · View at Google Scholar · View at Zentralblatt MATH · View at Scopus
  29. M. E. Burczynski, R. L. Peterson, N. C. Twine et al., “Molecular classification of Crohn's disease and ulcerative colitis patients using transcriptional profiles in peripheral blood mononuclear cells,” The Journal of Molecular Diagnostics, vol. 8, no. 1, pp. 51–61, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. L. Chen, C. Chu, and K. Feng, “Predicting the types of metabolic pathway of compounds using molecular fragments and sequential minimal optimization,” Combinatorial Chemistry & High Throughput Screening, vol. 19, no. 2, pp. 136–143, 2016. View at Publisher · View at Google Scholar · View at Scopus
  31. H. Mohabatkar, M. Mohammad Beigi, and A. Esmaeili, “Prediction of GABAA receptor proteins using the concept of Chou's pseudo-amino acid composition and support vector machine,” Journal of Theoretical Biology, vol. 281, no. 1, pp. 18–23, 2011. View at Publisher · View at Google Scholar · View at Scopus
  32. I. H. Witten and E. Frank, Data Mining: Practical Machine Learning Tools and Techniques, Morgan Kaufmann, San Francisco, Calif, USA, 2005.
  33. R. Kohavi, “A study of cross-validation and bootstrap for accuracy estimation and model selection,” in Proceedings of the International Joint Conference on Artificial Intelligence, Lawrence Erlbaum Associates Ltd, Quebec, Canada, 1995.
  34. L. Chen, J. Lu, N. Zhang, T. Huang, and Y.-D. Cai, “A hybrid method for prediction and repositioning of drug Anatomical Therapeutic Chemical classes,” Molecular BioSystems, vol. 10, no. 4, pp. 868–877, 2014. View at Publisher · View at Google Scholar · View at Scopus
  35. L. Chen, W.-M. Zeng, Y.-D. Cai, K.-Y. Feng, and K.-C. Chou, “Predicting anatomical therapeutic chemical (ATC) classification of drugs by integrating chemical-chemical interactions and similarities,” PLOS ONE, vol. 7, no. 4, Article ID e35254, 2012. View at Publisher · View at Google Scholar · View at Scopus
  36. C. von Mering, M. Huynen, D. Jaeggi, S. Schmidt, P. Bork, and B. Snel, “STRING: a database of predicted functional associations between proteins,” Nucleic Acids Research, vol. 31, no. 1, pp. 258–261, 2003. View at Publisher · View at Google Scholar · View at Scopus
  37. A. Franceschini, D. Szklarczyk, S. Frankild et al., “STRING v9.1: protein-protein interaction networks, with increased coverage and integration,” Nucleic Acids Research, vol. 41, no. 1, pp. D808–D815, 2013. View at Publisher · View at Google Scholar · View at Scopus
  38. M. Oti, B. Snel, M. A. Huynen, and H. G. Brunner, “Predicting disease genes using protein-protein interactions,” Journal of Medical Genetics, vol. 43, no. 8, pp. 691–698, 2006. View at Publisher · View at Google Scholar · View at Scopus
  39. M. Krauthammer, C. A. Kaufmann, T. C. Gilliam, and A. Rzhetsky, “Molecular triangulation: bridging linkage and molecular-network information for identifying candidate genes in Alzheimer's desease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 42, pp. 15148–15153, 2004. View at Publisher · View at Google Scholar · View at Scopus
  40. L. Franke, H. van Bakel, L. Fokkens, E. D. de Jong, M. Egmont-Petersen, and C. Wijmenga, “Reconstruction of a functional human gene network, with an application for prioritizing positional candidate genes,” The American Journal of Human Genetics, vol. 78, no. 6, pp. 1011–1025, 2006. View at Publisher · View at Google Scholar · View at Scopus
  41. S. Köhler, S. Bauer, D. Horn, and P. N. Robinson, “Walking the Interactome for Prioritization of Candidate Disease Genes,” The American Journal of Human Genetics, vol. 82, no. 4, pp. 949–958, 2008. View at Publisher · View at Google Scholar
  42. R. Jiang, M. Gan, and P. He, “Constructing a gene semantic similarity network for the inference of disease genes,” BMC Systems Biology, vol. 5, supplement 2, article no. S2, 2011. View at Publisher · View at Google Scholar
  43. H. Shi, J. Xu, G. Zhang et al., “Walking the interactome to identify human miRNA-disease associations through the functional link between miRNA targets and disease genes,” BMC Systems Biology, vol. 7, no. 1, article 101, 2013. View at Publisher · View at Google Scholar
  44. M. Jiang, Y. Chen, Y. Zhang et al., “Identification of hepatocellular carcinoma related genes with k-th shortest paths in a protein–protein interaction network,” Molecular BioSystems, vol. 9, no. 11, pp. 2720–2728, 2013. View at Publisher · View at Google Scholar
  45. L. Chen, Z. H. Xing, T. Huang, Y. Shu, G. Huang, and H.-P. Li, “Application of the shortest path algorithm for the discovery of breast cancer-related genes,” Current Bioinformatics, vol. 11, no. 1, pp. 51–58, 2016. View at Publisher · View at Google Scholar · View at Scopus
  46. T. Gui, X. Dong, R. Li, Y. Li, and Z. Wang, “Identification of hepatocellular carcinoma-related genes with a machine learning and network analysis,” Journal of Computational Biology, vol. 22, no. 1, pp. 63–71, 2015. View at Publisher · View at Google Scholar · View at Scopus
  47. M. Kitsak, S. Havlin, G. Paul, M. Riccaboni, F. Pammolli, and H. E. Stanley, “Betweenness centrality of fractal and nonfractal scale-free model networks and tests on real networks,” Physical Review E—Statistical, Nonlinear, and Soft Matter Physics, vol. 75, no. 5, part 2, Article ID 056115, 2007. View at Publisher · View at Google Scholar · View at Scopus
  48. D. W. Huang, B. T. Sherman, and R. A. Lempicki, “Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources,” Nature Protocols, vol. 4, no. 1, pp. 44–57, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. C. Li, H. Li, S. Wang et al., “The c-Fos and c-Jun from Litopenaeus vannamei play opposite roles in Vibrio parahaemolyticus and white spot syndrome virus infection,” Developmental and Comparative Immunology, vol. 52, no. 1, pp. 26–36, 2015. View at Publisher · View at Google Scholar · View at Scopus
  50. D. Thummuri, M. K. Jeengar, S. Shrivastava et al., “Thymoquinone prevents RANKL-induced osteoclastogenesis activation and osteolysis in an in vivo model of inflammation by suppressing NF-KB and MAPK Signalling,” Pharmacological Research, vol. 99, pp. 63–73, 2015. View at Publisher · View at Google Scholar · View at Scopus
  51. M. G. Welch, K. G. Margolis, Z. Li, and M. D. Gershon, “Oxytocin regulates gastrointestinal motility, inflammation, macromolecular permeability, and mucosal maintenance in mice,” American Journal of Physiology—Gastrointestinal and Liver Physiology, vol. 307, no. 8, pp. G848–G862, 2014. View at Publisher · View at Google Scholar · View at Scopus
  52. C. Auesukaree, H. Tochio, M. Shirakawa, Y. Kaneko, and S. Harashima, “Plc1p, Arg82p, and Kcs1p, enzymes involved in inositol pyrophosphate synthesis, are essential for phosphate regulation and polyphosphate accumulation in Saccharomyces cerevisiae,” Journal of Biological Chemistry, vol. 280, no. 26, pp. 25127–25133, 2005. View at Publisher · View at Google Scholar · View at Scopus
  53. D. Engelberg, R. Perlman, and A. Levitzki, “Transmembrane signaling in Saccharomyces cerevisiae as a model for signaling in metazoans: state of the art after 25 years,” Cellular Signalling, vol. 26, no. 12, pp. 2865–2878, 2014. View at Publisher · View at Google Scholar · View at Scopus
  54. Y. J. Chiang and R. J. Hodes, “Regulation of T cell development by c-Cbl: essential role of Lck,” International Immunology, vol. 27, no. 5, pp. 245–251, 2015. View at Publisher · View at Google Scholar
  55. M. D. Perron, S. Chowdhury, I. Aubry, E. Purisima, M. L. Tremblay, and H. U. Saragovi, “Allosteric noncompetitive small molecule selective inhibitors of CD45 tyrosine phosphatase suppress T-cell receptor signals and inflammation in vivo,” Molecular Pharmacology, vol. 85, no. 4, pp. 553–563, 2014. View at Publisher · View at Google Scholar · View at Scopus
  56. L. S. Toy, X. Y. Yio, A. Lin, S. Honig, and L. Mayer, “Defective expression of gp180, a novel CD8 ligand on intestinal epithelial cells, in inflammatory bowel disease,” Journal of Clinical Investigation, vol. 100, no. 8, pp. 2062–2071, 1997. View at Publisher · View at Google Scholar
  57. Z. Liao, L. Zhou, C. Wang et al., “Characteristics of TCRζ, ZAP-70, and FcɛRIγ Gene Expression in Patients with T- and NK/T-Cell Lymphoma,” DNA and Cell Biology, vol. 34, no. 3, pp. 201–207, 2015. View at Publisher · View at Google Scholar
  58. C. Sinclair, M. Ono, and B. Seddon, “A Zap70-dependent feedback circuit is essential for efficient selection of CD4 lineage thymocytes,” Immunology and Cell Biology, vol. 93, no. 4, pp. 406–416, 2015. View at Publisher · View at Google Scholar · View at Scopus
  59. D. Bouzid, H. Fourati, A. Amouri et al., “Association of ZAP70 and PTPN6, but not BANK1 or CLEC2D, with inflammatory bowel disease in the tunisian population,” Genetic Testing and Molecular Biomarkers, vol. 17, no. 4, pp. 321–326, 2013. View at Publisher · View at Google Scholar · View at Scopus
  60. M. Krzystek-Korpacka, D. Diakowska, J. Bania, and A. Gamian, “Expression stability of common housekeeping genes is differently affected by bowel inflammation and cancer: implications for finding suitable normalizers for inflammatory bowel disease studies,” Inflammatory Bowel Diseases, vol. 20, no. 7, pp. 1147–1156, 2014. View at Publisher · View at Google Scholar · View at Scopus
  61. W. Wang, T. Xia, and X. Yu, “Wogonin suppresses inflammatory response and maintains intestinal barrier function via TLR4-MyD88-TAK1-mediated NF-κB pathway in vitro,” Inflammation Research, vol. 64, no. 6, pp. 423–431, 2015. View at Publisher · View at Google Scholar · View at Scopus
  62. C. S. De Almeida, V. Andrade-Oliveira, N. O. S. Câmara, J. F. Jacysyn, and E. L. Faquim-Mauro, “Crotoxin from Crotalus durissus terrificus is able to down-modulate the acute intestinal inflammation in mice,” PLoS ONE, vol. 10, no. 4, Article ID e0121427, 2015. View at Publisher · View at Google Scholar · View at Scopus
  63. G. Brandhorst, S. Weigand, C. Eberle et al., “CD4+ immune response as a potential biomarker of patient reported inflammatory bowel disease (IBD) activity,” Clinica Chimica Acta, vol. 421, pp. 31–33, 2013. View at Publisher · View at Google Scholar · View at Scopus
  64. R. A. Gupta, M. N. Motiwala, N. G. Dumore, K. R. Danao, and A. B. Ganjare, “Effect of piperine on inhibition of FFA induced TLR4 mediated inflammation and amelioration of acetic acid induced ulcerative colitis in mice,” Journal of Ethnopharmacology, vol. 164, pp. 239–246, 2015. View at Publisher · View at Google Scholar · View at Scopus
  65. A. T. Cao, S. Yao, A. T. Stefka et al., “TLR4 regulates IFN-γ and IL-17 production by both thymic and induced Foxp3+ Tregs during intestinal inflammation,” Journal of Leukocyte Biology, vol. 96, no. 5, pp. 895–905, 2014. View at Publisher · View at Google Scholar
  66. D. Kohoutova, M. Pecka, M. Cihak, J. Cyrany, J. Maly, and J. Bures, “Prevalence of hypercoagulable disorders in inflammatory bowel disease,” Scandinavian Journal of Gastroenterology, vol. 49, no. 3, pp. 287–294, 2014. View at Publisher · View at Google Scholar · View at Scopus
  67. T. Bennike, S. Birkelund, A. Stensballe, and V. Andersen, “Biomarkers in inflammatory bowel diseases: current status and proteomics identification strategies,” World Journal of Gastroenterology, vol. 20, no. 12, pp. 3231–3244, 2014. View at Publisher · View at Google Scholar · View at Scopus
  68. M.-A. Meuwis, M. Fillet, L. Lutteri et al., “Proteomics for prediction and characterization of response to infliximab in Crohn's disease: a pilot study,” Clinical Biochemistry, vol. 41, no. 12, pp. 960–967, 2008. View at Publisher · View at Google Scholar · View at Scopus
  69. M.-A. Meuwis, M. Fillet, P. Geurts et al., “Biomarker discovery for inflammatory bowel disease, using proteomic serum profiling,” Biochemical Pharmacology, vol. 73, no. 9, pp. 1422–1433, 2007. View at Publisher · View at Google Scholar · View at Scopus
  70. H. Jiang, X. He, S. Wang et al., “A microtubule-associated zinc finger protein, BuGZ, regulates mitotic chromosome alignment by ensuring Bub3 stability and kinetochore targeting,” Developmental Cell, vol. 28, no. 3, pp. 268–281, 2014. View at Publisher · View at Google Scholar
  71. S. Bhattacharya, S. Srisuma, D. L. DeMeo et al., “Molecular biomarkers for quantitative and discrete COPD phenotypes,” American Journal of Respiratory Cell and Molecular Biology, vol. 40, no. 3, pp. 359–367, 2009. View at Publisher · View at Google Scholar
  72. T. Okamura, K. Fujio, M. Shibuya et al., “CD4+CD25LAG3+ regulatory T cells controlled by the transcription factor Egr-2,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 33, pp. 13974–13979, 2009. View at Publisher · View at Google Scholar
  73. R. J. Giannone, H. W. McDonald, G. B. Hurst, R.-F. Shen, Y. Wang, and Y. Liu, “The protein network surrounding the human telomere repeat binding factors TRF1, TRF2, and POT1,” PLoS ONE, vol. 5, no. 8, Article ID e12407, 2010. View at Publisher · View at Google Scholar · View at Scopus
  74. M. Zemljic, B. Pejkovic, I. Krajnc, and S. Lipovsek, “Biological pathways involved in the development of infammatory bowel disease,” Wiener Klinische Wochenschrift, vol. 126, no. 19-20, pp. 626–633, 2014. View at Publisher · View at Google Scholar · View at Scopus
  75. Y. Du, P. Liu, W. Zang et al., “BTG3 upregulation induces cell apoptosis and suppresses invasion in esophageal adenocarcinoma,” Molecular and Cellular Biochemistry, vol. 404, no. 1-2, pp. 31–38, 2015. View at Publisher · View at Google Scholar
  76. R. M. Ewing, P. Chu, F. Elisma et al., “Large-scale mapping of human protein–protein interactions by mass spectrometry,” Molecular Systems Biology, vol. 3, article no. 89, 2007. View at Publisher · View at Google Scholar
  77. B. Carvalho, C. Postma, S. Mongera et al., “Multiple putative oncogenes at the chromosome 20q amplicon contribute to colorectal adenoma to carcinoma progression,” Gut, vol. 58, no. 1, pp. 79–89, 2009. View at Publisher · View at Google Scholar · View at Scopus
  78. M. McDonnell, Y. Liang, A. Noronha et al., “Systemic toll-like receptor ligands modify B-cell responses in human inflammatory bowel disease,” Inflammatory Bowel Diseases, vol. 17, no. 1, pp. 298–307, 2011. View at Publisher · View at Google Scholar · View at Scopus
  79. R. Vitali, L. Stronati, A. Negroni et al., “Fecal HMGB1 is a novel marker of intestinal mucosal inflammation in pediatric inflammatory bowel disease,” The American Journal of Gastroenterology, vol. 106, no. 11, pp. 2029–2040, 2011. View at Publisher · View at Google Scholar · View at Scopus
  80. H. Takaishi, T. Kanai, A. Nakazawa et al., “Anti-high mobility group box 1 and box 2 non-histone chromosomal proteins (HMGB1/HMGB2) antibodies and anti-Saccharomyces cerevisiae antibodies (ASCA): accuracy in differentially diagnosing UC and CD and correlation with inflammatory bowel disease phenotype,” Journal of Gastroenterology, vol. 47, no. 9, pp. 969–977, 2012. View at Publisher · View at Google Scholar · View at Scopus
  81. M. D. Demarque, K. Nacerddine, H. Neyretkahn et al., “Sumoylation by Ubc9 regulates the stem cell compartment and structure and function of the intestinal epithelium in mice,” Gastroenterology, vol. 140, no. 1, pp. 286–296, 2011. View at Publisher · View at Google Scholar · View at Scopus
  82. N. S. Belaguli, M. Zhang, A.-H. Garcia, and D. H. Berger, “PIAS1 Is a GATA4 SUMO ligase that regulates GATA4-dependent intestinal promoters independent of SUMO ligase activity and GATA4 sumoylation,” PLoS ONE, vol. 7, no. 4, Article ID e35717, 2012. View at Publisher · View at Google Scholar · View at Scopus
  83. P. Zhou, Z. Wang, X. Yuan et al., “Mixed Lineage Leukemia 5 (MLL5) protein regulates cell cycle progression and E2F1-responsive gene expression via association with Host Cell Factor-1 (HCF-1),” The Journal of Biological Chemistry, vol. 288, no. 24, pp. 17532–17543, 2013. View at Publisher · View at Google Scholar · View at Scopus
  84. Y. J. Machida, Y. Machida, A. A. Vashisht, J. A. Wohlschlegel, and A. Dutta, “The deubiquitinating enzyme BAP1 regulates cell growth via interaction with HCF-1,” The Journal of Biological Chemistry, vol. 284, no. 49, pp. 34179–34188, 2009. View at Publisher · View at Google Scholar · View at Scopus
  85. C. Chapat and L. Corbo, “Novel roles of the CCR4-NOT complex,” Wiley Interdisciplinary Reviews: RNA, vol. 5, no. 6, pp. 883–901, 2014. View at Google Scholar
  86. A. S. Prabowo, J. van Scheppingen, A. M. Iyer et al., “Differential expression and clinical significance of three inflammation-related microRNAs in gangliogliomas,” Journal of Neuroinflammation, vol. 12, no. 1, article 97, 2015. View at Publisher · View at Google Scholar
  87. T. S. Elton, H. Selemon, S. M. Elton, and N. L. Parinandi, “Regulation of the MIR155 host gene in physiological and pathological processes,” Gene, vol. 532, no. 1, pp. 1–12, 2013. View at Publisher · View at Google Scholar · View at Scopus
  88. O. Loss and F. A. Stephenson, “Localization of the kinesin adaptor proteins trafficking kinesin proteins 1 and 2 in primary cultures of hippocampal pyramidal and cortical neurons,” Journal of Neuroscience Research, vol. 93, no. 7, pp. 1056–1066, 2015. View at Publisher · View at Google Scholar · View at Scopus
  89. R. A. Isidro, M. L. Cruz, A. A. Isidro et al., “Immunohistochemical expression of SP-NK-1R-EGFR pathway and VDR in colonic inflammation and neoplasia,” World Journal of Gastroenterology, vol. 21, no. 6, pp. 1749–1758, 2015. View at Publisher · View at Google Scholar
  90. P.-J. Chen, C. Huang, X.-M. Meng, and J. Li, “Epigenetic modifications by histone deacetylases: biological implications and therapeutic potential in liver fibrosis,” Biochimie, vol. 116, pp. 61–69, 2015. View at Publisher · View at Google Scholar · View at Scopus
  91. C. Felice, A. Lewis, A. Armuzzi, J. O. Lindsay, and A. Silver, “Review article: selective histone deacetylase isoforms as potential therapeutic targets in inflammatory bowel diseases,” Alimentary Pharmacology and Therapeutics, vol. 41, no. 1, pp. 26–38, 2015. View at Publisher · View at Google Scholar · View at Scopus
  92. I. A. Lee, A. Kamba, D. Low, and E. Mizoguchi, “Novel methylxanthine derivative-mediated anti-inflammatory effects in inflammatory bowel disease,” World Journal of Gastroenterology, vol. 20, no. 5, pp. 1127–1138, 2014. View at Publisher · View at Google Scholar
  93. S. Garcia-Maurino, A. Alcaide, and C. Dominguez, “Pharmacological control of autophagy: therapeutic perspectives in inflammatory bowel disease and colorectal cancer,” Current Pharmaceutical Design, vol. 18, no. 26, pp. 3853–3873, 2012. View at Publisher · View at Google Scholar
  94. H. Lee, S. Cha, M.-S. Lee, G. J. Cho, W. S. Choi, and K. Suk, “Role of antiproliferative B cell translocation gene-1 as an apoptotic sensitizer in activation-induced cell death of brain microglia,” Journal of Immunology, vol. 171, no. 11, pp. 5802–5811, 2003. View at Publisher · View at Google Scholar · View at Scopus
  95. C. A. Hamm and F. F. Costa, “Epigenomes as therapeutic targets,” Pharmacology & Therapeutics, vol. 151, pp. 72–86, 2015. View at Publisher · View at Google Scholar
  96. H. Liu, A. T. Cao, T. Feng et al., “TGF-β converts Th1 cells into Th17 cells through stimulation of Runx1 expression,” European Journal of Immunology, vol. 45, no. 4, pp. 1010–1018, 2015. View at Publisher · View at Google Scholar
  97. W. F. Wong, K. Kohu, A. Nakamura et al., “Runx1 deficiency in CD4+ T cells causes fatal autoimmune inflammatory lung disease due to spontaneous hyperactivation of cells,” Journal of Immunology, vol. 188, no. 11, pp. 5408–5420, 2012. View at Publisher · View at Google Scholar · View at Scopus
  98. G. P. Christophi, R. Rong, P. G. Holtzapple, P. T. Massa, and S. K. Landas, “Immune markers and differential signaling networks in ulcerative colitis and Crohn's disease,” Inflammatory Bowel Diseases, vol. 18, no. 12, pp. 2342–2356, 2012. View at Publisher · View at Google Scholar
  99. D. Salisbury and U. Bronas, “Inflammation and immune system contribution to the etiology of atherosclerosis: mechanisms and methods of assessment,” Nursing Research, vol. 63, no. 5, pp. 375–385, 2014. View at Publisher · View at Google Scholar · View at Scopus
  100. D. Dunkin, S. Mehandru, and J.-F. Colombel, “Immune cell therapy in IBD,” Digestive Diseases, vol. 32, supplement 1, pp. 61–66, 2014. View at Publisher · View at Google Scholar · View at Scopus
  101. J. B. Hurov, T. S. Stappenbeck, C. M. Zmasek et al., “Immune system dysfunction and autoimmune disease in mice lacking Emk (Par-1) protein kinase,” Molecular and Cellular Biology, vol. 21, no. 9, pp. 3206–3219, 2001. View at Publisher · View at Google Scholar · View at Scopus
  102. Y. Miwa, S. Yazaki, M. Iwamoto et al., “Functional difference between membrane-bound and soluble human thrombomodulin,” Transplantation, vol. 99, no. 4, pp. 702–709, 2015. View at Publisher · View at Google Scholar · View at Scopus
  103. M. C. Soult, Y. Dobrydneva, K. H. Wahab, L. D. Britt, and C. J. Sullivan, “Outer membrane vesicles alter inflammation and coagulation mediators,” Journal of Surgical Research, vol. 192, no. 1, pp. 134–142, 2014. View at Publisher · View at Google Scholar · View at Scopus
  104. J. Pekow, U. Dougherty, Y. Huang et al., “Gene signature distinguishes patients with chronic ulcerative colitis harboring remote neoplastic lesions,” Inflammatory Bowel Diseases, vol. 19, no. 3, pp. 461–470, 2013. View at Publisher · View at Google Scholar
  105. M. Lettau, M. Paulsen, D. Kabelitz, and O. Janssen, “FasL expression and reverse signalling,” Results and Problems in Cell Differentiation, vol. 49, pp. 49–61, 2009. View at Publisher · View at Google Scholar · View at Scopus
  106. T. J. Ślebioda and Z. Kmieć, “Tumour necrosis factor superfamily members in the pathogenesis of inflammatory bowel disease,” Mediators of Inflammation, vol. 2014, Article ID 325129, 15 pages, 2014. View at Publisher · View at Google Scholar
  107. W. Ben Aleya, I. Sfar, L. Mouelhi et al., “Association of Fas/Apo1 gene promoter (-670 A/G) polymorphism in Tunisian patients with IBD,” World Journal of Gastroenterology, vol. 15, no. 29, pp. 3643–3648, 2009. View at Publisher · View at Google Scholar · View at Scopus
  108. C. V. Antunes, A. E. Hallack Neto, C. R. Nascimento et al., “Anemia in Inflammatory bowel disease outpatients: prevalence, risk factors, and etiology,” BioMed Research International, vol. 2015, Article ID 728925, 7 pages, 2015. View at Publisher · View at Google Scholar
  109. J. W. Crott, Z. Liu, M. K. Keyes et al., “Moderate folate depletion modulates the expression of selected genes involved in cell cycle, intracellular signaling and folate uptake in human colonic epithelial cell lines,” Journal of Nutritional Biochemistry, vol. 19, no. 5, pp. 328–335, 2008. View at Publisher · View at Google Scholar · View at Scopus
  110. L. Pochini, M. Scalise, M. Galluccio, G. Pani, K. A. Siminovitch, and C. Indiveri, “The human OCTN1 (SLC22A4) reconstituted in liposomes catalyzes acetylcholine transport which is defective in the mutant L503F associated to the Crohn's disease,” Biochimica et Biophysica Acta—Biomembranes, vol. 1818, no. 3, pp. 559–565, 2012. View at Publisher · View at Google Scholar · View at Scopus
  111. K. Repnik and U. Potočnik, “Haplotype in the IBD5 region is associated with refractory Crohn's disease in Slovenian patients and modulates expression of the SLC22A5 gene,” Journal of Gastroenterology, vol. 46, no. 9, pp. 1081–1091, 2011. View at Publisher · View at Google Scholar · View at Scopus
  112. P. Sarlos, D. Varszegi, V. Csongei et al., “Susceptibility to ulcerative colitis in Hungarian patients determined by gene-gene interactions,” World Journal of Gastroenterology, vol. 20, no. 1, pp. 219–227, 2014. View at Publisher · View at Google Scholar · View at Scopus
  113. M. E. Gove, D. H. Rhodes, M. Pini et al., “Role of leptin receptor-induced STAT3 signaling in modulation of intestinal and hepatic inflammation in mice,” Journal of Leukocyte Biology, vol. 85, no. 3, pp. 491–496, 2008. View at Publisher · View at Google Scholar
  114. C. Benezech, S. Nayar, B. A. Finney et al., “CLEC-2 is required for development and maintenance of lymph nodes,” Blood, vol. 123, no. 20, pp. 3200–3207, 2014. View at Publisher · View at Google Scholar
  115. J. Shin, I. Yoon, J. Lim et al., “CD4+VEGFR1HIGH T cell as a novel Treg subset regulates inflammatory bowel disease in lymphopenic mice,” Cellular and Molecular Immunology, vol. 12, no. 5, pp. 592–603, 2015. View at Publisher · View at Google Scholar
  116. S. Maeda, K. Ohno, A. Fujiwara-Igarashi, K. Uchida, and H. Tsujimoto, “Changes in Foxp3-positive regulatory T cell number in the intestine of dogs with idiopathic inflammatory bowel disease and intestinal lymphoma,” Veterinary Pathology, vol. 53, no. 1, pp. 102–112, 2016. View at Publisher · View at Google Scholar · View at Scopus
  117. A. Di Sabatino, L. Rovedatti, R. Kaur et al., “Targeting gut T cell Ca2+ release-activated Ca2+ channels inhibits T cell cytokine production and T-box transcription factor T-bet in inflammatory bowel disease,” Journal of Immunology, vol. 183, no. 5, pp. 3454–3462, 2009. View at Publisher · View at Google Scholar · View at Scopus
  118. I. Gromova, P. Gromov, N. Kroman et al., “Immunoexpression analysis and prognostic value of BLCAP in breast cancer,” PLoS ONE, vol. 7, no. 9, Article ID e45967, 2012. View at Publisher · View at Google Scholar
  119. A. K.-F. Lo, K.-W. Lo, C.-W. Ko, L. S. Young, and C. W. Dawson, “Inhibition of the LKB1-AMPK pathway by the Epstein-Barr virus-encoded LMP1 promotes proliferation and transformation of human nasopharyngeal epithelial cells,” The Journal of Pathology, vol. 230, no. 3, pp. 336–346, 2013. View at Publisher · View at Google Scholar · View at Scopus
  120. L. Verstrepen and R. Beyaert, “Receptor proximal kinases in NF-κB signaling as potential therapeutic targets in cancer and inflammation,” Biochemical Pharmacology, vol. 92, no. 4, pp. 519–529, 2014. View at Publisher · View at Google Scholar
  121. Z. Liu, W. Zhang, M. Zhang, H. Zhu, C. Moriasi, and M. Zou, “Liver kinase B1 suppresses lipopolysaccharide-induced nuclear factor κB (NF-κB) activation in macrophages,” Journal of Biological Chemistry, vol. 290, no. 4, pp. 2312–2320, 2015. View at Publisher · View at Google Scholar
  122. F. Q. Calvo, M. Fillet, D. De Seny et al., “Biomarker discovery in asthma-related inflammation and remodeling,” Proteomics, vol. 9, no. 8, pp. 2163–2170, 2009. View at Publisher · View at Google Scholar · View at Scopus
  123. L. Beaugerie, “IBD and increased risk of cancer: what is the reality?” La Revue de l'Infirmière, vol. 63, no. 199, p. 28, 2014. View at Publisher · View at Google Scholar · View at Scopus
  124. M. C. Montesinos, A. Desai-Merchant, and B. N. Cronstein, “Promotion of wound healing by an agonist of adenosine A2A receptor is dependent on tissue plasminogen activator,” Inflammation, vol. 38, no. 6, pp. 2036–2041, 2015. View at Publisher · View at Google Scholar · View at Scopus
  125. Z. Shaghaghi, M. Bonyadi, M. H. Somi, and M. Khoshbaten, “Association of plasminogen activator inhibitor-1 gene polymorphism with inflammatory bowel disease in Iranian Azeri Turkish patients,” Saudi Journal of Gastroenterology, vol. 20, no. 1, pp. 54–58, 2014. View at Publisher · View at Google Scholar · View at Scopus
  126. I. E. Koutroubakis, A. Sfiridaki, G. Tsiolakidou, C. Coucoutsi, A. Theodoropoulou, and E. A. Kouroumalis, “Plasma thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 levels in inflammatory bowel disease,” European Journal of Gastroenterology and Hepatology, vol. 20, no. 9, pp. 912–916, 2008. View at Publisher · View at Google Scholar · View at Scopus
  127. E. Balboa-Beltran, M. J. Fernández-Seara, A. Pérez-Muñuzuri et al., “A novel stop mutation in the vascular endothelial growth factor-C gene (VEGFC) results in Milroy-like disease,” Journal of Medical Genetics, vol. 51, no. 7, pp. 475–478, 2014. View at Publisher · View at Google Scholar
  128. L. Le Guen, T. Karpanen, D. Schulte et al., “Ccbe1 regulates Vegfc-mediated induction of Vegfr3 signaling during embryonic lymphangiogenesis,” Development, vol. 141, no. 6, pp. 1239–1249, 2014. View at Publisher · View at Google Scholar · View at Scopus
  129. C. Tacconi, C. Correale, A. Gandelli et al., “Vascular endothelial growth factor C disrupts the endothelial lymphatic barrier to promote colorectal cancer invasion,” Gastroenterology, vol. 148, no. 7, pp. 1438.e8–1451.e8, 2015. View at Publisher · View at Google Scholar · View at Scopus
  130. S. D’Alessio, C. Correale, C. Tacconi et al., “VEGF-C-dependent stimulation of lymphatic function ameliorates experimental inflammatory bowel disease,” Journal of Clinical Investigation, vol. 124, no. 9, pp. 3863–3878, 2014. View at Publisher · View at Google Scholar
  131. C. S. Jorgensen, G. Levantino, G. Houen et al., “Determination of autoantibodies to annexin XI in systemic autoimmune diseases,” Lupus, vol. 9, no. 7, pp. 515–520, 2000. View at Publisher · View at Google Scholar · View at Scopus
  132. M. Heuser, D. B. Yap, M. Leung et al., “Loss of MII5 results in pleiotropic hematopoietic defects, reduced neutrophil immune function, and extreme sensitivity to DNA demethylation,” Blood, vol. 113, no. 7, pp. 1432–1443, 2009. View at Publisher · View at Google Scholar · View at Scopus
  133. S. Schulz, G. Chachami, L. Kozaczkiewicz et al., “Ubiquitin-specific protease-like 1 (USPL1) is a SUMO isopeptidase with essential, non-catalytic functions,” EMBO Reports, vol. 13, no. 10, pp. 930–938, 2012. View at Publisher · View at Google Scholar · View at Scopus
  134. J. Pärssinen, E.-L. Alarmo, S. Khan, R. Karhu, M. Vihinen, and A. Kallioniemi, “Identification of differentially expressed genes after PPM1D silencing in breast cancer,” Cancer Letters, vol. 259, no. 1, pp. 61–70, 2008. View at Publisher · View at Google Scholar · View at Scopus
  135. J. Z. Liu, S. van Sommeren, H. Huang et al., “Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations,” Nature Genetics, vol. 47, no. 9, pp. 979–986, 2015. View at Publisher · View at Google Scholar
  136. J. Piñero, N. Queralt-Rosinach, À. Bravo et al., “DisGeNET: a discovery platform for the dynamical exploration of human diseases and their genes,” Database, vol. 2015, Article ID bav028, 2015. View at Publisher · View at Google Scholar · View at Scopus