BMC Systems Biology | |
A simple knowledge-based mining method for exploring hidden key molecules in a human biomolecular network | |
Hiroyuki Aburatani1  Sigeo Ihara1  Shingo Tsuji2  | |
[1] Genome Science Division, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan;Komaba Open Laboratory, The University of Tokyo, Tokyo, Japan | |
关键词: Cancer research; Omics data analysis; Network data mining; Knowledge-based analysis; | |
Others : 1143600 DOI : 10.1186/1752-0509-6-124 |
|
received in 2012-02-08, accepted in 2012-07-25, 发布年份 2012 | |
【 摘 要 】
Background
In the functional genomics analysis domain, various methodologies are available for interpreting the results produced by high-throughput biological experiments. These methods commonly use a list of genes as an analysis input, and most of them produce a more complicated list of genes or pathways as the results of the analysis. Although there are several network-based methods, which detect key nodes in the network, the results tend to include well-studied, major hub genes.
Results
To mine the molecules that have biological meaning but to fewer degrees than major hubs, we propose, in this study, a new network-based method for selecting these hidden key molecules based on virtual information flows circulating among the input list of genes. The human biomolecular network was constructed from the Pathway Commons database, and a calculation method based on betweenness centrality was newly developed. We validated the method with the ErbB pathway and applied it to practical cancer research data. We were able to confirm that the output genes, despite having fewer edges than major hubs, have biological meanings that were able to be invoked by the input list of genes.
Conclusions
The developed method, named NetHiKe (Network-based Hidden Key molecule miner), was able to detect potential key molecules by utilizing the human biomolecular network as a knowledge base. Thus, it is hoped that this method will enhance the progress of biological data analysis in the whole-genome research era.
【 授权许可】
2012 Tsuji et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20150329141508598.pdf | 1252KB | download | |
Figure 5. | 58KB | Image | download |
Figure 4. | 90KB | Image | download |
Figure 3. | 96KB | Image | download |
Figure 2. | 111KB | Image | download |
Figure 1. | 53KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
Figure 4.
Figure 5.
【 参考文献 】
- [1]Schaefer CF, Anthony K, Krupa S, Buchoff J, Day M, Hannay T, Buetow KH: PID: the Pathway Interaction Database. Nucleic Acids Res 2009, 37:D674-D679.
- [2]Pathway Interaction Database [http://pid.nci.nih.gov/ webcite]
- [3]Huang daW, Sherman BT, Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009, 4:44-57.
- [4]Spirin V, Mirny LA: Protein complexes and functional modules in molecular networks. Proc Natl Acad Sci USA 2003, 100:12123-12128.
- [5]Georgii E, Dietmann S, Uno T, Pagel P, Tsuda K: Enumeration of condition-dependent dense modules in protein interaction networks. Bioinformatics 2009, 25:933-940.
- [6]Cerami E, Demir E, Schultz N, Taylor BS, Sander C: Automated network analysis identifies core pathways in glioblastoma. PLoS ONE 2010, 5:e8918.
- [7]Yamada T, Bork P: Evolution of biomolecular networks: lessons from metabolic and protein interactions. Nat Rev Mol Cell Biol 2009, 10:791-803.
- [8]Valente TW, Coronges K, Lakon C, Costenbader E: How Correlated Are Network Centrality Measures? Connect (Tor) 2008, 28:16-26.
- [9]Vallabhajosyula RR, Chakravarti D, Lutfeali S, Ray A, Raval A: Identifying hubs in protein interaction networks. PLoS ONE 2009, 4:e5344.
- [10]Agarwal S, Deane CM, Porter MA, Jones NS: Revisiting date and party hubs: novel approaches to role assignment in protein interaction networks. PLoS Comput Biol 2010, 6:e1000817.
- [11]Zotenko E, Mestre J, O’Leary DP, Przytycka TM: Why do hubs in the yeast protein interaction network tend to be essential: reexamining the connection between the network topology and essentiality. PLoS Comput Biol 2008, 4:e1000140.
- [12]Lin CY, Chin CH, Wu HH, Chen SH, Ho CW, Ko MT: Hubba: hub objects analyzer–a framework of interactome hubs identification for network biology. Nucleic Acids Res 2008, 36:W438-W443.
- [13]Wu J, Vallenius T, Ovaska K, Westermarck J, Makela TP, Hautaniemi S: Integrated network analysis platform for protein-protein interactions. Nat Methods 2009, 6:75-77.
- [14]Brohee S, Faust K, Lima-Mendez G, Sand O, Janky R, Vanderstocken G, Deville Y, van Helden J: NeAT: a toolbox for the analysis of biological networks, clusters, classes and pathways. Nucleic Acids Res 2008, 36:W444-W451.
- [15]Freeman L C: A set of measures of centrality based on betweenness. Sociometry 1977, 40:35-41.
- [16]Fortunato S, Latora V, Marchiori M: Method to find community structures based on information centrality. Phys Rev E Stat Nonlin Soft Matter Phys 2004, 70:056104.
- [17]Baselga J, Swain SM: Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat Rev Cancer 2009, 9:463-475.
- [18]Schoeberl B, Pace EA, Fitzgerald JB, Harms BD, Xu L, Nie L, Linggi B, Kalra A, Paragas V, Bukhalid R, Grantcharova V, Kohli N, West KA, Leszczyniecka M, Feldhaus MJ, Kudla AJ, Nielsen UB: Therapeutically targeting ErbB3: a key node in ligand-induced activation of the ErbB receptor-PI3K axis. Sci Signal 2009, 2:ra31.
- [19]Normanno N, De Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR, Carotenuto A, De Feo G, Caponigro F, Salomon DS: Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 2006, 366:2-16.
- [20]McLendon R, Friedman A, Bigner D, Van Meir EG, Brat DJ, Mastrogianakis GM, Olson JJ, Mikkelsen T, Lehman N, Aldape K, Yung WK, Bogler O, Weinstein JN, VandenBerg S, Berger M, Prados M, Muzny D, Morgan M, Scherer S, Sabo A, Nazareth L, Lewis L, Hall O, Zhu Y, Ren Y, Alvi O, Yao J, Hawes A, Jhangiani S, Fowler G, San Lucas A, Kovar C, Cree A, Dinh H, Santibanez J, Joshi V, Gonzalez-Garay ML, Miller CA, Milosavljevic A, Donehower L, Wheeler DA, Gibbs RA, Cibulskis K, Sougnez C, Fennell T, Mahan S, Wilkinson J, Ziaugra L, Onofrio R, Bloom T, Nicol R, Ardlie K, Baldwin J, Gabriel S, Lander ES, Ding L, Fulton RS, McLellan MD, Wallis J, Larson DE, Shi X, Abbott R, Fulton L, Chen K, Koboldt DC, Wendl MC, Meyer R, Tang Y, Lin L, Osborne JR, Dunford-Shore BH, Miner TL, Delehaunty K, Markovic C, Swift G, Courtney W, Pohl C, Abbott S, Hawkins A, Leong S, Haipek C, Schmidt H, Wiechert M, Vickery T, Scott S, Dooling DJ, Chinwalla A, Weinstock GM, Mardis ER, Wilson RK, Getz G, Winckler W, Verhaak RG, Lawrence MS, O’Kelly M, Robinson J, Alexe G, Beroukhim R, Carter S, Chiang D, Gould J, Gupta S, Korn J, Mermel C, Mesirov J, Monti S, Nguyen H, Parkin M, Reich M, Stransky N, Weir BA, Garraway L, Golub T, Meyerson M, Chin L, Protopopov A, Zhang J, Perna I, Aronson S, Sathiamoorthy N, Ren G, Yao J, Wiedemeyer WR, Kim H, Kong SW, Xiao Y, Kohane IS, Seidman J, Park PJ, Kucherlapati R, Laird PW, Cope L, Herman JG, Weisenberger DJ, Pan F, Van den Berg D, Van Neste L, Yi JM, Schuebel KE, Baylin SB, Absher DM, Li JZ, Southwick A, Brady S, Aggarwal A, Chung T, Sherlock G, Brooks JD, Myers RM, Spellman PT, Purdom E, Jakkula LR, Lapuk AV, Marr H, Dorton S, Choi YG, Han J, Ray A, Wang V, Durinck S, Robinson M, Wang NJ, Vranizan K, Peng V, Van Name E, Fontenay GV, Ngai J, Conboy JG, Parvin B, Feiler HS, Speed TP, Gray JW, Brennan C, Socci ND, Olshen A, Taylor BS, Lash A, Schultz N, Reva B, Antipin Y, Stukalov A, Gross B, Cerami E, Wang WQ, Qin LX, Seshan VE, Villafania L, Cavatore M, Borsu L, Viale A, Gerald W, Sander C, Ladanyi M, Perou CM, Hayes DN, Topal MD, Hoadley KA, Qi Y, Balu S, Shi Y, Wu J, Penny R, Bittner M, Shelton T, Lenkiewicz E, Morris S, Beasley D, Sanders S, Kahn A, Sfeir R, Chen J, Nassau D, Feng L, Hickey E, Barker A, Gerhard DS, Vockley J, Compton C, Vaught J, Fielding P, Ferguson ML, Schaefer C, Zhang J, Madhavan S, Buetow KH, Collins F, Good P, Guyer M, Ozenberger B, Peterson J, Thomson E: Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 2008, 455:1061-1068.
- [21]Sieg DJ, Hauck CR, Ilic D, Klingbeil CK, Schaefer E, Damsky CH, Schlaepfer DD: FAK integrates growth-factor and integrin signals to promote cell migration. Nat Cell Biol 2000, 2:249-256.
- [22]Lin AH, Eliceiri BP, Levin EG: FAK mediates the inhibition of glioma cell migration by truncated 24 kDa FGF-2. Biochem Biophys Res Commun 2009, 382:503-507.
- [23]Halder J, Lin YG, Merritt WM, Spannuth WA, Nick AM, Honda T, Kamat AA, Han LY, Kim TJ, Lu C, Tari AM, Bornmann W, Fernandez A, Lopez-Berestein G, Sood AK: Therapeutic efficacy of a novel focal adhesion kinase inhibitor TAE226 in ovarian carcinoma. Cancer Res 2007, 67:10976-10983.
- [24]Hochwald SN, Nyberg C, Zheng M, Zheng D, Wood C, Massoll NA, Magis A, Ostrov D, Cance WG, Golubovskaya VM: A novel small molecule inhibitor of FAK decreases growth of human pancreatic cancer. Cell Cycle 2009, 8:2435-2443.
- [25]Beierle EA, Ma X, Stewart J, Nyberg C, Trujillo A, Cance WG, Golubovskaya VM: Inhibition of focal adhesion kinase decreases tumor growth in human neuroblastoma. Cell Cycle 2010, 9:1005-1015.
- [26]Hu Y, Pioli PD, Siegel E, Zhang Q, Nelson J, Chaturbedi A, Mathews MS, Ro DI, Alkafeef S, Hsu N, Hamamura M, Yu L, Hess KR, Tromberg BJ, Linskey ME, Zhou YH: EFEMP1 suppresses malignant glioma growth and exerts its action within the tumor extracellular compartment. Mol Cancer 2011, 10:123. BioMed Central Full Text
- [27]Evans IM, Yamaji M, Britton G, Pellet-Many C, Lockie C, Zachary IC, Frankel P: Neuropilin-1 signaling through p130Cas tyrosine phosphorylation is essential for growth factor-dependent migration of glioma and endothelial cells. Mol Cell Biol 2011, 31:1174-1185.
- [28]Kim JH, Zheng LT, Lee WH, Suk K: Pro-apoptotic role of integrin β3 in glioma cells. J Neurochem 2011, 117:494-503.
- [29]Tatard VM, Xiang C, Biegel JA, Dahmane N: ZNF238 is expressed in postmitotic brain cells and inhibits brain tumor growth. Cancer Res 2010, 70:1236-1246.
- [30]Hecker TP, Grammer JR, Gillespie GY, Stewart J, Gladson CL: Focal adhesion kinase enhances signaling through the Shc/extracellular signal-regulated kinase pathway in anaplastic astrocytoma tumor biopsy samples. Cancer Res 2002, 62:2699-2707.
- [31]Cerami EG, Gross BE, Demir E, Rodchenkov I, Babur O, Anwar N, Schultz N, Bader GD, Sander C: Pathway Commons, a web resource for biological pathway data. Nucleic Acids Res 2011, 39(Database issue):D685—D690.
- [32]Stark C, Breitkreutz BJ, Reguly T, Boucher L, Breitkreutz A, Tyers M: BioGRID: a general repository for interaction datasets. Nucleic Acids Res 2006, 34:D535—D539.
- [33]The Cancer Cell Map [http://cancer.cellmap.org/cellmap/ webcite]
- [34]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: Human Protein Reference Database–2009 update. Nucleic Acids Res 2009, 37:D767—D772.
- [35]Karp PD, Ouzounis CA, Moore-Kochlacs C, Goldovsky L, Kaipa P, Ahrén D, Tsoka S, Darzentas N, Kunin V, López-Bigas N: Expansion of the BioCyc collection of pathway/genome databases to 160 genomes. Nucleic Acids Res 2005, 33:6083-6089.
- [36]SBCNY [http://www.sbcny.org webcite]
- [37]Aranda B, Achuthan P, Alam-Faruque Y, Armean I, Bridge A, Derow C, Feuermann M, Ghanbarian AT, Kerrien S, Khadake J, Kerssemakers J, Leroy C, Menden M, Michaut M, Montecchi-Palazzi L, Neuhauser SN, Orchard S, Perreau V, Roechert B, van Eijk K, Hermjakob H: The IntAct molecular interaction database in 2010. Nucleic Acids Res 2010, 38:D525—D531.
- [38]Ceol A, Chatr Aryamontri A, Licata L, Peluso D, Briganti L, Perfetto L, Castagnoli L, Cesareni G: MINT, the molecular interaction database: 2009 update. Nucleic Acids Res 2010, 38:D532—D539.
- [39]Matthews L, Gopinath G, Gillespie M, Caudy M, Croft D, de Bono B, Garapati P, Hemish J, Hermjakob H, Jassal B, Kanapin A, Lewis S, Mahajan S, May B, Schmidt E, Vastrik I, Wu G, Birney E, Stein L, D’Eustachio P: Reactome knowledgebase of human biological pathways and processes. Nucleic Acids Res 2009, 37:D619—D622.
- [40]Davison A, Hinkley D: Chapter 4 Tests. In Bootstrap Methods and their Application. Cambridge University Press, New York; 1997-1997.
- [41]Wheeler DL, Dunn EF, Harari PM: Understanding resistance to EGFR inhibitors-impact on future treatment strategies. Nat Rev Clin Oncol 2010, 7:493-507.
- [42]ErbB/HER SIgnaling (Cell Signaling Technology) [http://www.cellsignal.com/reference/pathway/ErbB_HER.html webcite]
- [43]Smoot ME, Ono K, Ruscheinski J, Wang PL, Ideker T: Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics 2011, 27:431-432.
- [44]Kan Z, Jaiswal BS, Stinson J, Janakiraman V, Bhatt D, Stern HM, Yue P, Haverty PM, Bourgon R, Zheng J, Moorhead M, Chaudhuri S, Tomsho LP, Peters BA, Pujara K, Cordes S, Davis DP, Carlton VE, Yuan W, Li L, Wang W, Eigenbrot C, Kaminker JS, Eberhard DA, Waring P, Schuster SC, Modrusan Z, Zhang Z, Stokoe D, de Sauvage FJ, Faham M, Seshagiri S: Diverse somatic mutation patterns and pathway alterations in human cancers. Nature 2010, 466:869-873.
- [45]The Cancer Genome Atlas Data Portal [http://tcga-portal.nci.nih.gov/tcga-portal/AnomalySearch.jsp webcite]