期刊论文详细信息
BMC Bioinformatics
Hierarchical decomposition of dynamically evolving regulatory networks
Ahmet Ay2  Dihong Gong1  Tamer Kahveci1 
[1] Department of Computer and Information Science and Engineering, University of Florida, Gainesville 32611, FL, USA
[2] Departments of Biology and Mathematics, Colgate University, Hamilton 13346, NY, USA
关键词: Network dynamics;    Gene regulatory networks;    Hierarchy;   
Others  :  1232566
DOI  :  10.1186/s12859-015-0529-9
 received in 2014-10-27, accepted in 2015-03-09,  发布年份 2015
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【 摘 要 】

Background

Gene regulatory networks describe the interplay between genes and their products. These networks control almost every biological activity in the cell through interactions. The hierarchy of genes in these networks as defined by their interactions gives important insights into how these functions are governed. Accurately determining the hierarchy of genes is however a computationally difficult problem. This problem is further complicated by the fact that an intrinsic characteristic of regulatory networks is that the wiring of interactions can change over time. Determining how the hierarchy in the gene regulatory networks changes with dynamically evolving network topology remains to be an unsolved challenge.

Results

In this study, we develop a new method, named D-HIDEN (Dynamic-HIerarchical DEcomposition of Networks) to find the hierarchy of the genes in dynamically evolving gene regulatory network topologies. Unlike earlier methods, which recompute the hierarchy from scratch when the network topology changes, our method adapts the hierarchy based on the wiring of the interactions only for the nodes which have the potential to move in the hierarchy.

Conclusions

We compare D-HIDEN to five currently available hierarchical decomposition methods on synthetic and real gene regulatory networks. Our experiments demonstrate that D-HIDEN significantly outperforms existing methods in running time, accuracy, or both. Furthermore, our method is robust against dynamic changes in hierarchy. Our experiments on human gene regulatory networks suggest that our method may be used to reconstruct hierarchy in gene regulatory networks.

【 授权许可】

   
2015 Ay et al.; licensee BioMed Central.

【 预 览 】
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【 参考文献 】
  • [1]She M, Ye X, Yan Y, Howit C, Belgard M, Ma W. Gene networks in the synthesis and deposition of protein polymers during grain development of wheat. Funct Integr Genomics. 2011; 11(1):23-35.
  • [2]Watson E, Walhout AJM. Caenorhabditis elegans metabolic gene regulatory networks govern the cellular economy. Trends Endocrinol Metab. 2014. doi:10.1016/j.tem.2014.03.004.
  • [3]Peter IS, Davidson EH. Evolution of gene regulatory networks controlling body plan development. Cell. 2011; 144(6):970-85.
  • [4]Ó’Maoiléidigh DS, Graciet E, Wellmer F. Gene networks controlling Arabidopsis thaliana flower development. New Phytol. 2014; 201(1):16-30.
  • [5]Buckingham M, Rigby PWJ. Gene regulatory networks and transcriptional mechanisms that control myogenesis. Dev Cell. 2014; 28(3):225-38.
  • [6]Lander AD. How cells know where they are. Science. 2013; 339(6122):923-7.
  • [7]Csikász-Nagy A, Palmisano A, Zámborszky J. Molecular network dynamics of cell cycle control: transitions to start and finish. Methods Mol Biol. 2011; 761:277-91.
  • [8]Belz GT, Nutt SL. Transcriptional programming of the dendritic cell network. Nat Rev Immunol. 2012; 12(2):101-13.
  • [9]Barabási A-L, Oltvai ZN. Network biology: understanding the cell’s functional organization. Nat Rev Genet. 2004; 5:101-13.
  • [10]Barabási A AR. Emergence of Scaling in Random Networks. Science. 1999; 286(5439):509-12.
  • [11]Yu H, Gerstein M. Genomic analysis of the hierarchical structure of regulatory networks. Proc Natl Acad Sci USA. 2006; 103:14724-31.
  • [12]Jothi R, Balaji S, Wuster A, Grochow JA, Gsponer J, Przytycka TM et al.. Genomic analysis reveals a tight link between transcription factor dynamics and regulatory network architecture. Mol Syst Biol. 2009; 5:294.
  • [13]Hartsperger ML, Strache R, Stümpflen V. HiNO: An approach for inferring hierarchical organization from regulatory networks. PLoS ONE. 2010; 5. doi:10.1371/journal.pone.0013698.
  • [14]Gulsoy G, Bandhyopadhyay N, Kahveci T. HIDEN: Hierarchical decomposition of regulatory networks. 2012. doi:10.1186/1471-2105- 13-250.
  • [15]Bhardwaj N, Kim PM, Gerstein MB. Rewiring of transcriptional regulatory networks: hierarchy, rather than connectivity, better reflects the importance of regulators. Sci Signaling. 2010; 3:79.
  • [16]Bhardwaj N, Yan K-K, Gerstein MB. Analysis of diverse regulatory networks in a hierarchical context shows consistent tendencies for collaboration in the middle levels. Proc Nat Acad Sci USA. 2010; 107:6841-6846.
  • [17]Ma H-W, Buer J, Zeng A-P. Hierarchical structure and modules in the Escherichia coli transcriptional regulatory network revealed by a new top-down approach. BMC Bioinformatics. 2004; 5:199.
  • [18]Ma H-W, Kumar B, Ditges U, Gunzer F, Buer J, Zeng A-P. An extended transcriptional regulatory network of Escherichia coli and analysis of its hierarchical structure and network motifs. Nucleic Acids Res. 2004; 32:6643-9.
  • [19]Cosentino Lagomarsino M, Jona P, Bassetti B, Isambert H. Hierarchy and feedback in the evolution of the Escherichia coli transcription network. Proc Nat Acad Sci USA. 2007; 104:5516-20.
  • [20]Freyre-González JA, Alonso-Pavón JA, Treviño-Quintanilla LG, Collado-Vides J. Functional architecture of Escherichia coli: new insights provided by a natural decomposition approach. Genome Biol. 2008; 9:154.
  • [21]Neph S, Stergachis AB, Reynolds A, Sandstrom R, Borenstein E, Stamatoyannopoulos JA. Circuitry and dynamics of human transcription factor regulatory networks. Cell. 2012; 150:1274-86.
  • [22]Han J-DJ, Bertin N, Hao T, Goldberg DS, Berriz GF, Zhang LV et al.. Evidence for dynamically organized modularity in the yeast protein-protein interaction network. Nature. 2004; 430:88-93.
  • [23]Babu MM, Luscombe NM, Aravind L, Gerstein M, Teichmann SA. Structure and evolution of transcriptional regulatory networks. 2004. doi:10.1016/j.sbi.2004.05.004.
  • [24]Harbison CT, Gordon DB, Lee TI, Rinaldi NJ, Macisaac KD, Danford TW et al.. Transcriptional regulatory code of a eukaryotic genome. Nature. 2004; 431:99-104.
  • [25]Scott J, Ideker T, Karp RM, Sharan R. Efficient Algorithms for Detecting Signaling Pathways in Protein Interaction Networks. J Comput Biol. 2006; 13(2):133-44.
  • [26]Rohwedel J, Maltsev V, Bober E, Arnold HH, Hescheler J, Wobus AM. Muscle cell differentiation of embryonic stem cells reflects myogenesis in vivo: developmentally regulated expression of myogenic determination genes and functional expression of ionic currents. Dev Biol. 1994; 164:87-101.
  • [27]Brunetti A, Goldfine ID. Role of myogenin is myoblast differentiation and its regulation by fibroblast growth factor. J Biol Chem. 1990; 265:5960-3.
  • [28]Arnold HH, Braun T. Targeted inactivation of myogenic factor genes reveals their role during mouse myogenesis: A review. Int J Dev Biol. 1996; 40:345-53.
  • [29]Hasty P, Bradley A, Morris JH, Edmondson DG, Venuti JM, Olson EN et al.. Muscle deficiency and neonatal death in mice with a targeted mutation in the myogenin gene. Nature. 1993; 364:501-6.
  • [30]Wilson KD, Hu S, Venkatasubrahmanyam S, Fu J-D, Sun N, Abilez OJ et al.. Dynamic microRNA expression programs during cardiac differentiation of human embryonic stem cells: role for miR-499. Circ Cardiovasc Genet. 2010; 3:426-35.
  • [31]Gossett LA, Kelvin DJ, Sternberg EA, Olson EN. A new myocyte-specific enhancer-binding factor that recognizes a conserved element associated with multiple muscle-specific genes. Mol Cell Biol. 1989; 9:5022-33.
  • [32]Potthoff MJ, Olson EN. MEF2: a central regulator of diverse developmental programs. Dev (Cambridge, England). 2007; 134:4131-40.
  • [33]Kyba M, Perlingeiro RCR, Hoover RR, Lu C-W, Pierce J, Daley GQ. Enhanced hematopoietic differentiation of embryonic stem cells conditionally expressing Stat5. Proc Nat Acad Sci USA. 2003; 100 Suppl 1:11904-10.
  • [34]Santos SC, Lacronique V, Bouchaert I, Monni R, Bernard O, Gisselbrecht S et al.. Constitutively active STAT5 variants induce growth and survival of hematopoietic cells through a PI 3-kinase/Akt dependent pathway. Oncogene. 2001; 20:2080-90.
  • [35]Schuringa JJ, Chung KY, Morrone G, Moore MAS. Constitutive activation of STAT5A promotes human hematopoietic stem cell self-renewal and erythroid differentiation. J Exp Med. 2004; 200:623-35.
  • [36]de Groot RP, Raaijmakers JA, Lammers JW, Jove R, Koenderman L. STAT5 activation by BCR-Abl contributes to transformation of K562 leukemia cells. Blood. 1999; 94:1108-12.
  • [37]Lancrin C, Mazan M, Stefanska M, Patel R, Lichtinger M, Costa G et al.. GFI1 and GFI1B control the loss of endothelial identity of hemogenic endothelium during hematopoietic commitment. Blood. 2012; 120:314-22.
  • [38]Hock H, Hamblen MJ, Rooke HM, Schindler JW, Saleque S, Fujiwara Y et al.. Gfi-1 restricts proliferation and preserves functional integrity of haematopoietic stem cells. Nature. 2004; 431:1002-7.
  • [39]Lidonnici MR, Audia A, Soliera AR, Prisco M, Ferrari-Amorotti G, Waldron T et al.. Expression of the transcriptional repressor Gfi-1 is regulated by C/EBP α and is involved in its proliferation and colony formation-inhibitory effects in p210BCR/ABL-expressing cells. Cancer Res. 2010; 70:7949-59.
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