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Shannon entropy approach reveals relevant genes in Alzheimer’s disease


Autoři: Alfonso Monaco aff001;  Nicola Amoroso aff001;  Loredana Bellantuono aff002;  Eufemia Lella aff002;  Angela Lombardi aff001;  Anna Monda aff002;  Andrea Tateo aff002;  Roberto Bellotti aff001;  Sabina Tangaro aff001
Působiště autorů: Istituto Nazionale di Fisica Nucleare (INFN), Sezione di Bari, Bari, Italy aff001;  Department of Physics ‘Michelangelo Merlin’, University of Bari ‘Aldo Moro’, Bari, Italy aff002
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0226190

Souhrn

Alzheimer’s disease (AD) is the most common type of dementia and affects millions of people worldwide. Since complex diseases are often the result of combinations of gene interactions, microarray data and gene co-expression analysis can provide tools for addressing complexity. Our study aimed to find groups of interacting genes that are relevant in the development of AD. In this perspective, we implemented a method proposed in a previous work to detect gene communities linked to AD. Our strategy combined co-expression network analysis with the study of Shannon entropy of the betweenness. We analyzed the publicly available GSE1297 dataset, achieved from the GEO database in NCBI, containing hippocampal gene expression of 9 control and 22 AD human subjects. Co-expressed genes were clustered into different communities. Two communities of interest (composed by 72 and 39 genes) were found by calculating the correlation coefficient between communities and clinical features. The detected communities resulted stable, replicated on two independent datasets and mostly enriched in pathways closely associated with neuro-degenative diseases. A comparison between our findings and other module detection techniques showed that the detected communities were more related to AD phenotype. Lastly, the hub genes within the two communities of interest were identified by means of a centrality analysis and a bootstrap procedure. The communities of the hub genes presented even stronger correlation with clinical features. These findings and further explorations on the detected genes could shed light on the genetic aspects related with physiological aspects of Alzheimer’s disease.

Klíčová slova:

Algorithms – Alzheimer's disease – Clustering algorithms – Gene expression – Gene regulatory networks – Genetic networks – Hierarchical clustering – Network analysis


Zdroje

1. Brettschneider J, Tredici KD, Lee VM, Trojanowski JQ. Spreading of pathology in neurodegenerative diseases: a focus on human studies. Nature Reviews Neurology. 2015;16(2): 109. doi: 10.1038/nrn3887

2. Prince M, Comas-Herrera A, Knapp M, Guerchet M, Karagiannidou M. World Alzheimer report 2016: improving health- care for people living with dementia: coverage quality and costs now and in the future. Alzheimer’s Disease International. 2016.

3. Noble W, Olm V, Takata K, Casey E, Mary O, Meyerson J, et al. Cdk5 is a key factor in tau aggregation and tangle formation in vivo. Neuron. 2003;38(4): 555–565. doi: 10.1016/s0896-6273(03)00259-9 12765608

4. Johnson GV, Bailey CD. Tau, where are we now? Journal of Alzheimer’s Disease. 2002;4: 375–398. doi: 10.3233/jad-2002-4505 12446970

5. Tanzi RE, Bertram L. New frontiers in Alzheimer’s disease genetics. Neuron. 2001;32: 181–184. doi: 10.1016/s0896-6273(01)00476-7 11683989

6. Klein WL, Krafft GA, Finch CE. Targeting small Abeta oligomers: the solution to an Alzheimer’s disease conundrum? Trends in Neurosciences. 2001;24(4): 219–224. doi: 10.1016/s0166-2236(00)01749-5 11250006

7. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science. 2012;297(5580): 353–356. doi: 10.1126/science.1072994

8. Mucke L, Masliah E, Yu GQ, Mallory M, Rockenstein EM, Tatsuno G. et al. High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. Journal of Neuroscience. 2000;20: 4050–4058. doi: 10.1523/JNEUROSCI.20-11-04050.2000 10818140

9. Gouras GK, Tsai J, Naslund J, Vincent B, Edgar M, Checler F, et al. Intraneuronal Abeta42 accumulation in human brain. The American Journal of Pathology. 2000;156: 15–20. doi: 10.1016/s0002-9440(10)64700-1 10623648

10. Aksenov MY, Aksenova MV, Butterfield DA, Geddes JW, Markesbery WR. Protein oxidation in the brain in Alzheimer’s disease. Neuroscience. 2001;103: 373–383. doi: 10.1016/s0306-4522(00)00580-7 11246152

11. Gibson GE. Intraneuronal Abeta42 accumulation in human brain. Free Radical Biology & Medicine. 2002;32: 1061–1070.

12. Gemma C, Mesches MH, Sepesi B, Choo K, Holmes DB, Bickford PC. Diets Enriched in Foods with High Antioxidant Activity Reverse Age-Induced Decreases in Cerebellar β-Adrenergic Function and Increases in Proinflammatory Cytokines. Journal of Neuroscience. 2002;22: 6114–6120. doi: 10.1523/JNEUROSCI.22-14-06114.2002 12122072

13. Mrak RE, Griffin WS. Interleukin-1, neuroinflammation, and Alzheimer’s disease. Neurobiology of Aging. 2001;22: 903–908. doi: 10.1016/s0197-4580(01)00287-1 11754997

14. Blalock EM, Geddes JW, Chen KC, Porter NM, Markesbery WR, Landfield PW. Incipient Alzheimer’s disease: microarray correlation analyses reveal major transcriptional and tumor suppressor responses. Proceedings of the National Academy of Sciences. 2004;101(7):2173–2178. doi: 10.1073/pnas.0308512100

15. Monaco A, Sforza G, Amoroso N, Antonacci M, Bellotti R, de Tommaso M, et al. The PERSON project: a serious brain- computer interface game for treatment in cognitive impairment. Health and Technology. 2019;9(2): 123–133. doi: 10.1007/s12553-018-0258-y

16. Wilson RJ. Introduction to Graph theory. 4th ed. Addison Wesley, Longman; 1996.

17. Langfelder P, Horvath S. Wgcna: an R package for weighted correlation network analysis. BMC bioinformatics. 2008;9(1):1. doi: 10.1186/1471-2105-9-559

18. Dawson JA, Kendziorski C. An empirical Bayesian approach for identifying differential coexpression in high-throughput experiments Biometrics. 2012;68: 455–465. doi: 10.1111/j.1541-0420.2011.01688.x 22004327

19. Liu BH, Yu H, Tu K, Li C, Li YX and Li YY. DCGL: An R package for identifying differentially coexpressed genes and links from gene expression microarray data. Bioinformatics. 2010;26: 2637–2638. doi: 10.1093/bioinformatics/btq471 20801914

20. Zhang B, Horvath S. A general framework for weighted gene co-expression network analysis. Statistical Applications in Genetics and Molecular Biology. 2005;4:Article17. doi: 10.2202/1544-6115.1128 16646834

21. Monaco A, Monda A, Amoroso N, Bertolino A, Blasi G, Di Carlo P, et al. A complex network approach reveals a pivotal substructure of genes linked to schizophrenia. PLoS ONE. 2018;13(1): e0190110. doi: 10.1371/journal.pone.0190110 29304112

22. Choobdar S, Ahsen ME, Crawford J, Tomasoni M, Fang T, Lamparter D, Li J, et al. Assessment of network module identification across complex diseases. Nature Methods. 2019;16: 843–852. doi: 10.1038/s41592-019-0509-5 31471613

23. Chung N, Zhang XD, Kreamer A, Locco L, Kuan P, Bartz S, et al. Median Absolute Deviation to Improve Hit Selection for Genome-Scale RNAi Screens. Journal of Biomolecular Screening. 2008;13: 149. doi: 10.1177/1087057107312035 18216396

24. Spitz A, Gimmler A, Stoeck T, Zweig KA, Horvat EA. Assessing Low-Intensity Relationships in Complex Networks. PLoS ONE. 2016;11(4): e0152536. doi: 10.1371/journal.pone.0152536 27096435

25. Pinney JW, Westhead DR. Betweenness-based decomposition methods for social and biological networks. Interdisciplinary Statistics and Bioinformatics. 2006;25: 87–90.

26. Dunn R, Dudbridge F, Sanderson CM. The use of edge-betweenness clustering to investigate biological function in protein interaction networks. BMC bioinformatics. 2005;1: 6–39.

27. Brandes U. On variants of shortest-path betweenness centrality and their generic computation. Social Networks. 2008;30(2): 136–145. doi: 10.1016/j.socnet.2007.11.001

28. Shannon CE. A Mathematical Theory of Communication. The Bell System Technical Journal. 1958;27: 379–423. doi: 10.1002/j.1538-7305.1948.tb01338.x

29. West J, Bianconi G, Severini S, Teschendorff AE. Differential network entropy reveals cancer system hallmarks. Scientific Reports. 2012;2: 802. doi: 10.1038/srep00802 23150773

30. Fortunato S. Community Detection in Graphs. Physics Report. 2010;486: 75–174. doi: 10.1016/j.physrep.2009.11.002

31. Ravasz E. Detecting hierarchical modularity in biological networks. Computational Systems Biology. 2009;541: 145–160. doi: 10.1007/978-1-59745-243-4_7

32. Newman MEJ. Fast algorithm for detecting community structure in networks. Physical Review E. 2004;69(6): 066133. doi: 10.1103/PhysRevE.69.066133

33. Newman MEJ, Girvan M. Finding and evaluating community structure in networks. Physical Review E. 2004;69(2): 026113. doi: 10.1103/PhysRevE.69.026113

34. Arenas A, Diaz-Guilera A. Synchronization and modularity in complex networks. European Physical Journal ST. 2007;143: 19–25. doi: 10.1140/epjst/e2007-00066-2

35. Lozano S, Duch J, Arenas A. Analysis of large social datasets by community detection. European Physical Journal ST. 2007;143: 257–259. doi: 10.1140/epjst/e2007-00098-6

36. Clauset A, Newman MEJ, Moore C. Finding community structure in very large networks. Physical Review E. 2004;70(6): 066111. doi: 10.1103/PhysRevE.70.066111

37. Sieberts SK, Schadt EE. Moving toward a system genetics view of disease. Mammalian Genome. 2007;18(6–7): 389–401. doi: 10.1007/s00335-007-9040-6 17653589

38. Foroushani A, Agrahari R, Docking R, Chang L, Duns G, Hudoba M, et al. Large-scale gene network analysis reveals the significance of extracellular matrix pathway and homeobox genes in acute myeloid leukemia: an introduction to the Pigengene package and its applications. BMC Medical Genomics. 2017;10:16. doi: 10.1186/s12920-017-0253-6 28298217

39. Oldham MC, Horvath S, Geschwind DH. Conservation and evolution of gene coexpression networks in human and chimpanzee brains. Proceedings of the National Academy of Sciences. 2006; 103(47): 17973–17978. doi: 10.1073/pnas.0605938103

40. Liang JW, Fang ZY, Huang Y, Liuyang ZY, Zhang XL, Wanga JL, et al. Application of Weighted Gene Co-Expression Network Analysis to Explore the Key Genes in Alzheimer’s Disease Journal of Alzheimer’s Disease. 2018; 65: 1353–1364. doi: 10.3233/JAD-180400 30124448

41. Subramanian A, Kuehn H, Gould J, Tamayo P, Mesirov JP. GSEA-P: A desktop application for Gene Set Enrichment Analysis. Bioinformatics. 2007;23(23): 3251–3253. doi: 10.1093/bioinformatics/btm369 17644558

42. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proceedings of the National Academy of Sciences. 2005;102(43): 15545–15550. doi: 10.1073/pnas.0506580102

43. Benjamini Y, Hochberg Y. Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. Royal Statistical Society. 1995;57(1): 289–300.

44. Kleinberg J. Authoritative sources in a hyperlinked environment. Journal of the ACM. 1999; 46(5): 604–632. doi: 10.1145/324133.324140

45. Mooney CZ, Duval RD. Bootstrapping: a nonparametric approach to statistical inference. 1st ed. Newbury Park, CA: Sage University Paper; 1993.

46. Nankervis JC. Computational algorithms for double bootstrap confidence intervals. Computational Statistics & Data Analysis. 2005;49(2): 461–474. doi: 10.1016/j.csda.2004.05.023

47. Vijaymeena MK, Kavitha K. A Survey on Similarity Measures in Text Mining. Machine Learning and Applications: An International Journal. 2016:3(1): 19–28. doi: 10.5121/mlaij.2016.3103

48. Saelenes W, Cannoodt R, Saeys Y. A comprehensive evalutation of module detection methods for gene expression data. Nature Communications. 2005;9:1090. doi: 10.1038/s41467-018-03424-4

49. Rousseeuw P.J. Silhouettes: A graphical aid to the interpretation and validation of cluster analysis. Journal of Computational and Applied Mathematics. 1987;20: 53–65. doi: 10.1016/0377-0427(87)90125-7

50. Bezdek JC. Cluster validity with fuzzy sets Journal of Cybernetics. 1974;3: 58–73. doi: 10.1080/01969727308546047

51. Frey BJ, Dueck D. Clustering by passing messages between data points. Science. 2007;315: 972–976. doi: 10.1126/science.1136800 17218491

52. Chavez Montes RA, Coello G, Gonzalez-Aguilera KL, et al. ARACNe-based inference, using curated microarray data, of Arabidopsis thaliana root transcriptional regulatory networks. BMC Plant Biology. 2014;14: 97. doi: 10.1186/1471-2229-14-97 24739361

53. Huynh-Thu VA, Irrthum A, Wehenkel L, et al. Inferring regulatory networks from expression data using tree-based methods. PLoS One 2010;5: e0012776. doi: 10.1371/journal.pone.0012776

54. Peng J, Wang P, Zhou N, Zhu J. Partial Correlation Estimation by Joint Sparse Regression Models. Journal of the American Statistical Association. 2009;104(486): 735–746. doi: 10.1198/jasa.2009.0126 19881892

55. van Dam S, Võsa U, van der Graaf A, Franke L, de Magalhães JP. Gene co-expression analysis for functional classification and gene–disease predictions. Briefings in Bioinformatics. 2018;19(4): 575–592. doi: 10.1093/bib/bbw139 28077403

56. Allen JD, Xie Y, Chen M, Girard L, Xiao G. Comparing Statistical Methods for Constructing Large Scale Gene Networks. PLoS One. 2012;7(1): e29348. doi: 10.1371/journal.pone.0029348 22272232

57. Lanke V, Moolamalla STR, Roy D, Vinod PK. Integrative Analysis of Hippocampus Gene Expression Profiles Identifies Network Alterations in Aging and Alzheimer’s Disease. Frontiers in Aging Neuroscience. 2018; 23;10:153. doi: 10.3389/fnagi.2018.00153

58. Moustafa AA, Hassan M, Hewedi DH, Hewedi I, Garami JK, Al Ashwalet H, et al. Genetic underpinnings in Alzheimer’s disease—a review. Reviews in the Neurosciences. 2017; 29(1). doi: 10.1515/revneuro-2017-0036

59. Lambert JC, Ibrahim-Verbaas CA, Harold D, Naj AC, Sims R, Bellenguez C, et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s diseas. Nature Genetics. 2013;45(12):1452–8. doi: 10.1038/ng.2802 24162737

60. Seyfried NT, Dammer EB, Swarup V, Nandakumar D, Duong DM, Yin L, et al. A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer’s Disease. Cell Systems. 2017;4(1): 60–72. doi: 10.1016/j.cels.2016.11.006 27989508

61. Miller AJ, Oldham MC, Geschwind DH. A Systems Level Analysis of Transcriptional Changes inAlzheimer’s Disease and Normal Aging. The Journal of Neuroscience. 2008;28(6): 1410–1420. doi: 10.1523/JNEUROSCI.4098-07.2008 18256261

62. Bird TD. Genetic aspects of Alzheimer disease. Genetics in Medicine. 2008;10(4): 231–239. doi: 10.1097/GIM.0b013e31816b64dc 18414205

63. Ertekin-Taner N. Genetics of Alzheimer’s disease: a centennial review. Neurologic Clinics. 2007;25(3): 611–667. doi: 10.1016/j.ncl.2007.03.009 17659183

64. Mattson MP. Pathways towards and away from Alzheimer’s disease. Nature. 2004;430(7000): 631–639. doi: 10.1038/nature02621 15295589

65. Naj CA, Schellenberg GD. Genomic Variants, Genes, and Pathways of Alzheimer’s Disease: An Overview. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 2017;174(1): 5–26. doi: 10.1002/ajmg.b.32499

66. Zabel C, Nguyen HP, Hin SC, Hartl D, Mao L and Klose J. Proteasome and oxidative phoshorylation changes may explain why aging is a risk factor for neurodegenerative disorders. Journal of Proteomics. 2010;73: 2230–2238. doi: 10.1016/j.jprot.2010.08.008 20813214

67. Shoffner JM. Oxidative phosphorylation defects and Alzheimer’s disease. Neurogenetics. 1997;1(1): 13–9. doi: 10.1007/s100480050002 10735269

68. Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th ed. New York: W.H. Freeman; 2002.

69. Swerdlow RH. Mitochondria and Mitochondrial Cascades in Alzheimer’s Disease. Journal of Alzheimer’s Disease. 2018;62(3): 1403–1416. doi: 10.3233/JAD-170585 29036828

70. Atamna H, Frey WH. Mechanisms of mitochondrial dysfunction and energy deficiency in Alzheimer’s disease. Mitochondrion. 2007;7(5): 297–310. doi: 10.1016/j.mito.2007.06.001 17625988

71. Atamna H, Newberry J, Erlitzki R, Schultz CS, Ames BN. Biotin deficiency inhibits heme synthesis and impairs mitochondria in human lung fibroblasts. Journal of Nutrition. 2007;137: 25–30. doi: 10.1093/jn/137.1.25 17182796

72. Ponka P. Cell biology of heme. The American Journal of the Medical Sciences. 1999;318: 241–256. doi: 10.1097/00000441-199910000-00004 10522552

73. Cadonic C, Sabbir MC, Albens BC. Mechanisms of Mitochondrial Dysfunction in Alzheimer’s Disease. Molecular Neurobiology. 2016;53(9): 6078–6090. doi: 10.1007/s12035-015-9515-5 26537901

74. Bubber P, Haroutunian V., Fisch G, Blass JP, Gibson GE: Mitochondrial abnormalities in Alzheimer brain: mechanistic implications. Annals of Neurology. 2005;57: 695–703. doi: 10.1002/ana.20474 15852400

75. Amoroso N, La Rocca M, Bruno S, Maggipinto T, Monaco A, Bellotti R, et al. Multiplex Networks for Early Diagnosis of Alzheimer’s Disease. Frontiers in Aging Neuroscience. 2018; 10: 365. doi: 10.3389/fnagi.2018.00365 30487745


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