Please wait a minute...
Quantitative Biology

ISSN 2095-4689

ISSN 2095-4697(Online)

CN 10-1028/TM

邮发代号 80-971

Quantitative Biology  2019, Vol. 7 Issue (4): 313-326   https://doi.org/10.1007/s40484-019-0180-y
  本期目录
WIPER: Weighted in-Path Edge Ranking for biomolecular association networks
Zongliang Yue1, Thanh Nguyen1, Eric Zhang2, Jianyi Zhang2, Jake Y. Chen1,2,3()
1. Informatics Institute, School of Medicine, University of Alabama, Birmingham, AL 35233, USA
2. Department of Biomedical Engineering, University of Alabama, Birmingham, AL 35233, USA
3. Department of Computer Science, University of Alabama, Birmingham, AL 35233, USA
 全文: PDF(2126 KB)   HTML
Abstract

Background: In network biology researchers generate biomolecular networks with candidate genes or proteins experimentally-derived from high-throughput data and known biomolecular associations. Current bioinformatics research focuses on characterizing candidate genes/proteins, or nodes, with network characteristics, e.g., betweenness centrality. However, there have been few research reports to characterize and prioritize biomolecular associations (“edges”), which can represent gene regulatory events essential to biological processes.

Method: We developed Weighted In-Path Edge Ranking (WIPER), a new computational algorithm which can help evaluate all biomolecular interactions/associations (“edges”) in a network model and generate a rank order of every edge based on their in-path traversal scores and statistical significance test result. To validate whether WIPER worked as we designed, we tested the algorithm on synthetic network models.

Results: Our results showed WIPER can reliably discover both critical “well traversed in-path edges”, which are statistically more traversed than normal edges, and “peripheral in-path edges”, which are less traversed than normal edges. Compared with other simple measures such as betweenness centrality, WIPER provides better biological interpretations. In the case study of analyzing postanal pig hearts gene expression, WIPER highlighted new signaling pathways suggestive of cardiomyocyte regeneration and proliferation. In the case study of Alzheimer’s disease genetic disorder association, WIPER reports SRC:APP, AR:APP, APP:FYN, and APP:NES edges (gene-gene associations) both statistically and biologically important from PubMed co-citation.

Conclusion: We believe that WIPER will become an essential software tool to help biologists discover and validate essential signaling/regulatory events from high-throughput biology data in the context of biological networks.

Availability: The free WIPER API is described at discovery.informatics.uab.edu/wiper/

收稿日期: 2019-06-01      出版日期: 2019-12-31
Corresponding Author(s): Jake Y. Chen   
 引用本文:   
. [J]. Quantitative Biology, 2019, 7(4): 313-326.
Zongliang Yue, Thanh Nguyen, Eric Zhang, Jianyi Zhang, Jake Y. Chen. WIPER: Weighted in-Path Edge Ranking for biomolecular association networks. Quant. Biol., 2019, 7(4): 313-326.
 链接本文:  
https://academic.hep.com.cn/qb/CN/10.1007/s40484-019-0180-y
https://academic.hep.com.cn/qb/CN/Y2019/V7/I4/313
Fig.1  
Fig.2  
Fig.3  
Fig.4  
Fig.5  
Fig.6  
Fig.7  
Edge Degree We UFC Rank p-value PubMed score
SRC:APP 262 252.11 2.96 8 1.00E?03 3.65
AR:APP 222 248 2.91 11 1.38E?03 1.35
APP:FYN 226 223.18 2.62 37 4.75E?03 1.47
APP:NES 178 179.01 2.1 260 3.28E?02 0.54
PARK2:AR 110 176.5 2.07 291 3.68E?02 0.47
ESR1:PSEN1 134 168.6 1.98 408 5.15E?02 1.25
AR:CDK5 119 166.31 1.95 446 5.58E?02 0.61
Tab.1  
Fig.8  
Fig.9  
1 J. De Las Rivas, and C. Fontanillo, (2010) Protein-protein interactions essentials: key concepts to building and analyzing interactome networks. PLOS Comput. Biol., 6, e1000807
https://doi.org/10.1371/journal.pcbi.1000807 pmid: 20589078
2 Y. Qian, , Y. Li, , M. Zhang, , G. Ma, and F. Lu, (2017) Quanfifying edge significance on maintaining global connectivity. Sci. Rep., 7, 45380
3 T. Werner, , S. M. Dombrowski, , C. Zgheib, , F. A. Zouein, , H. L. Keen, , M. Kurdi, and G. W. Booz, (2013) Elucidating functional context within microarray data by integrated transcription factor-focused gene-interaction and regulatory network analysis. Eur. Cytokine Netw., 24, 75–90
https://doi.org/10.1684/ecn.2013.0336 pmid: 23822978
4 P. Jiang, , H. Wang, , W. Li, , C. Zang, , B. Li, , Y. J. Wong, , C. Meyer, , J. S. Liu, , J. C. Aster, and X. S. Liu, (2015) Network analysis of gene essentiality in functional genomics experiments. Genome Biol., 16, 239
https://doi.org/10.1186/s13059-015-0808-9 pmid: 26518695
5 Z. Dezsö, , Y. Nikolsky, , T. Nikolskaya, , J. Miller, , D. Cherba, , C. Webb, and A. Bugrim, (2009) Identifying disease-specific genes based on their topological significance in protein networks. BMC Syst. Biol., 3, 36
https://doi.org/10.1186/1752-0509-3-36 pmid: 19309513
6 J. Ni, , M. Koyuturk, , H. Tong, , J. Haines, , R. Xu, and X. Zhang, (2016) Disease gene prioritization by integrating tissue-specific molecular networks using a robust multi-network model. BMC Bioinformatics, 17, 453
https://doi.org/10.1186/s12859-016-1317-x pmid: 27829360
7 Z. Bar-Joseph, , A. Gitter, and I. Simon, (2012) Studying and modelling dynamic biological processes using time-series gene expression data. Nat. Rev. Genet., 13, 552–564
https://doi.org/10.1038/nrg3244 pmid: 22805708
8 C. Klein, , A. Marino, , M. F. Sagot, , P. Vieira Milreu, and M. Brilli, (2012) Structural and dynamical analysis of biological networks. Brief. Funct. Genomics, 11, 420–433
https://doi.org/10.1093/bfgp/els030 pmid: 22908211
9 O. V. Popik, , O. V. Saik, , E. D. Petrovskiy, , B. Sommer, , R. Hofestädt, , I. N. Lavrik, and V. A. Ivanisenko, (2014) Analysis of signaling networks distributed over intracellular compartments based on protein-protein interactions. BMC Genomics, 15, S7
https://doi.org/10.1186/1471-2164-15-S12-S7 pmid: 25564293
10 A. Chaudhuri, and J. Chant, (2005) Protein-interaction mapping in search of effective drug targets. BioEssays, 27, 958–969
https://doi.org/10.1002/bies.20284 pmid: 16108076
11 A. A. Ivanov, , F. R. Khuri, and H. Fu, (2013) Targeting protein-protein interactions as an anticancer strategy. Trends Pharmacol. Sci., 34, 393–400
https://doi.org/10.1016/j.tips.2013.04.007 pmid: 23725674
12 A. Herrero, , A. Pinto, , P. Colón-Bolea, , B. Casar, , M. Jones, , L. Agudo-Ibáñez, , R. Vidal, , S. P. Tenbaum, , P. Nuciforo, , E. M. Valdizán, , et al. (2015) Small molecule inhibition of erk dimerization prevents tumorigenesis by RAS-ERK pathway oncogenes. Cancer Cell, 28, 170–182
https://doi.org/10.1016/j.ccell.2015.07.001 pmid: 26267534
13 B. T. Hennessy, , D. L. Smith, , P. T. Ram, , Y. Lu, and G. B. Mills, (2005) Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat. Rev. Drug Discov., 4, 988–1004
https://doi.org/10.1038/nrd1902 pmid: 16341064
14 D. Hanahan, and R. A. Weinberg, (2011) Hallmarks of cancer: the next generation. Cell, 144, 646–674
https://doi.org/10.1016/j.cell.2011.02.013 pmid: 21376230
15 T. Theodosiou, , G. Efstathiou, , N. Papanikolaou, , N. C. Kyrpides, , P. G. Bagos, , I. Iliopoulos, and G. A Pavlopoulos, . (2017) NAP: The Network Analysis Profiler, a web tool for easier topological analysis and comparison of medium-scale biological networks. BMC Res. Notes, 10, 278
https://doi.org/10.1186/s13104-017-2607-8 pmid: 28705239
16 Z. Wang, , L. Dueñas-Osorio, and J. E. Padgett, (2015) A new mutually reinforcing network node and link ranking algorithm. Sci. Rep., 5, 15141
https://doi.org/10.1038/srep15141 pmid: 26492958
17 J. Wang, , M. Li, , H. Wang, , and Y. Pan, (2012) Identification of essential proteins based on edge clustering coefficient. IEEE/ACM Trans. Comput. Biol. Bioinform. 9, 1070–1080
18 Y. Wang, , H. Sun, , W. Du, , E. Blanzieri, , G. Viero, , Y. Xu, and Y. Liang, (2014) Identification of essential proteins based on ranking edge-weights in protein-protein interaction networks. PLoS One, 9, e108716
https://doi.org/10.1371/journal.pone.0108716 pmid: 25268881
19 M. Krüger, , M. Moser, , S. Ussar, , I. Thievessen, , C. A. Luber, , F. Forner, , S. Schmidt, , S. Zanivan, , R. Fässler, and M. Mann, (2008) SILAC mouse for quantitative proteomics uncovers kindlin-3 as an essential factor for red blood cell function. Cell, 134, 353–364
https://doi.org/10.1016/j.cell.2008.05.033 pmid: 18662549
20 J. Chen, , R. Pandey, , and T. M. Nguyen, (2017) Happi-2: A comprehensive and high-quality map of human annotated and predicted protein interactions. BMC genomics
21 Y. Hulovatyy, , R. W. Solava, and T. Milenković, (2014) Revealing missing parts of the interactome via link prediction. PLoS One, 9, e90073
https://doi.org/10.1371/journal.pone.0090073 pmid: 24594900
22 G. G. Chowdhury, (2010) Introduction to Modern Information Retrieval. Facet publishing
23 C. Lei, and J. Ruan, (2013) A novel link prediction algorithm for reconstructing protein-protein interaction networks by topological similarity. Bioinformatics, 29, 355–364
https://doi.org/10.1093/bioinformatics/bts688 pmid: 23235927
24 R. W. Solava, , R. P. Michaels, and T. Milenkovic, (2012) Graphlet-based edge clustering reveals pathogen-interacting proteins. Bioinformatics, 28, i480–i486
https://doi.org/10.1093/bioinformatics/bts376 pmid: 22962470
25 O. Kuchaiev, , M. Rasajski, , D. J. Higham, and N. Przulj, (2009) Geometric de-noising of protein-protein interaction networks. PLOS Comput. Biol., 5, e1000454
https://doi.org/10.1371/journal.pcbi.1000454 pmid: 19662157
26 W. Zhu, , E. Zhang, , M. Zhao, , Z. Chong, , C. Fan, , Y. Tang, , J. D. Hunter, , A. V. Borovjagin, , G. P. Walcott, , J. Y. Chen, , et al. (2018) Regenerative potential of neonatal porcine hearts. Circulation, 138, 2809–2816
https://doi.org/10.1161/CIRCULATIONAHA.118.034886 pmid: 30030418
27 J. Tromp, , A. van der Pol, , I. T. Klip, , R. A. de Boer, , T. Jaarsma, , W. H. van Gilst, , A. A. Voors, , D. J. van Veldhuisen, and P. van der Meer, (2014) Fibrosis marker syndecan-1 and outcome in patients with heart failure with reduced and preserved ejection fraction. Circ Heart Fail, 7, 457–462
https://doi.org/10.1161/CIRCHEARTFAILURE.113.000846 pmid: 24647119
28 J. Hescheler, and B. K. Fleischmann, (2000) Integrins and cell structure: powerful determinants of heart development and heart function. Cardiovasc. Res., 47, 645–647
https://doi.org/10.1016/S0008-6363(00)00164-4 pmid: 10974214
29 J. Chaufty, , S. E. Sullivan, and A. Ho, (2012) Intracellular amyloid precursor protein sorting and amyloid-β secretion are regulated by Src-mediated phosphorylation of Mint2. J. Neurosci., 32, 9613–9625
https://doi.org/10.1523/JNEUROSCI.0602-12.2012 pmid: 22787047
30 S. S. Minami, , T. G. Clifford, , H. S. Hoe, , Y. Matsuoka, , and G. W. Rebeck, (2012) Fyn knock-down increases Aβ, decreases phospho-tau, and worsens spatial learning in 3×Tg-AD mice. Neurobiol. Aging,33, e815–824
31 X. Wan, , W. Wang, , J. Liu, and T. Tong, (2014) Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med. Res. Methodol., 14, 135
https://doi.org/10.1186/1471-2288-14-135 pmid: 25524443
32 M. Dorigo, and M. Birattari, (2011) Ant Colony Optimization. In: Encyclopedia of Machine Learning, pp. 36–39. Springer
33 E. W. Dijkstra, (1959) A note on two problems in connexion with graphs. Numer. Math., 1, 269–271
https://doi.org/10.1007/BF01386390
34 P. J. Hale, , A. M. López-Yunez, and J. Y. Chen, (2012) Genome-wide meta-analysis of genetic susceptible genes for Type 2 Diabetes. BMC Syst. Biol., 6, S16
https://doi.org/10.1186/1752-0509-6-S3-S16 pmid: 23281828
35 Z. Yue, , Q. Zheng, , M. T. Neylon, , M. Yoo, , J. Shin, , Z. Zhao, , A. C. Tan, and J. Y. Chen, (2018) PAGER 2.0: an update to the pathway, annotated-list and gene-signature electronic repository for Human Network Biology. Nucleic Acids Res., 46, D668–D676
https://doi.org/10.1093/nar/gkx1040 pmid: 29126216
36 J. Rice, (2006) Mathematical Statistics and Data Analysis. Duxbury Press
37 G. Tosadori, , I. Bestvina, , F. Spoto, , C. Laudanna, and G. Scardoni, (2016) Creating, generating and comparing random network models with NetworkRandomizer. F1000 Res., 5, 2524
https://doi.org/10.12688/f1000research.9203.1 pmid: 29188012
38 E. Y. Yu, , D. B. Chen, and J. Y. Zhao, (2018) Identifying critical edges in complex networks. Sci. Rep., 8, 14469
https://doi.org/10.1038/s41598-018-32631-8 pmid: 30262804
39 J. I. F. Bass, , A. Diallo, , J. Nelson, , J. M. Soto, , C. L. Myers, and A. J. M. Walhout, (2013) Using networks to measure similarity between genes: association index selection. Nat. Methods, 10, 1169–1176
https://doi.org/10.1038/nmeth.2728 pmid: 24296474
40 X.-Q. Cheng, , F.-X. Ren, , H.-W. Shen, , Z.-K. Zhang, and T. Zhou, (2010) Bridgeness: A local index on edge significance in maintaining global connectivity. J. Stat. Mech., 2010, P10011
https://doi.org/10.1088/1742-5468/2010/10/P10011
41 K. Saito, , M. Kimura, , K. Ohara, and H. Motoda, (2016) Detecting critical links in complex network to maintain information flow/reachability. In: PRICAI 2016: Trends in Artificial Intelligence, pp. 419–432. Springer
42 S. L. Wang, , X. L. Li, and J. Fang, (2012) Finding minimum gene subsets with heuristic breadth-first search algorithm for robust tumor classification. BMC Bioinformatics, 13, 178
https://doi.org/10.1186/1471-2105-13-178 pmid: 22830977
43 D. Szklarczyk, , J. H. Morris, , H. Cook, , M. Kuhn, , S. Wyder, , M. Simonovic, , A. Santos, , N. T. Doncheva, , A. Roth, , P. Bork, , et al. (2017) The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res., 45, D362–D368
https://doi.org/10.1093/nar/gkw937 pmid: 27924014
44 L. Bertram, , M. B. McQueen, , K. Mullin, , D. Blacker, and R. E. Tanzi, (2007) Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nat. Genet., 39, 17–23
https://doi.org/10.1038/ng1934 pmid: 17192785
45 Z. Yue, , M. M. Kshirsagar, , T. Nguyen, , C. Suphavilai, , M. T. Neylon, , L. Zhu, , T. Ratliff, and J. Y. Chen, (2015) PAGER: constructing PAGs and new PAG-PAG relationships for network biology. Bioinformatics, 31, i250–i257
https://doi.org/10.1093/bioinformatics/btv265 pmid: 26072489
[1] QB-19180-OF-CJ_suppl_1 Download
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed