Oncofinder, a new method for the analysis of intracellular signaling pathway activation using transcriptomic data

被引:65
作者
Buzdin, Anton A. [1 ,2 ,3 ,4 ]
Zhavoronkov, Alex A. [1 ,2 ,4 ]
Korzinkin, Mikhail B. [1 ,5 ]
Venkova, Larisa S. [5 ]
Zenin, Alexander A. [5 ]
Smirnov, Philip Yu. [5 ]
Borisov, Nikolay M. [1 ,4 ,5 ]
机构
[1] Pathway Pharmaceut Ltd, Hong Kong, Hong Kong, Peoples R China
[2] Dr Rogachev Fed Res Ctr Pediat Hematol Oncol & Im, Moscow, Russia
[3] Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow, Russia
[4] Moscow Inst Phys & Technol, Dolgoprudnyi, Russia
[5] Burnasyan Fed Med Biophys Ctr, Moscow, Russia
来源
FRONTIERS IN GENETICS | 2014年 / 5卷
关键词
NETWORK;
D O I
10.3389/fgene.2014.00055
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
We propose a new biomathematical method, OncoFinder, for both quantitative and qualitative analysis of the intracellular signaling pathway activation (SPA). This method is universal and may be used for the analysis of any physiological, stress, malignancy and other perturbed conditions at the molecular level. In contrast to the other existing techniques for aggregation and generalization of the gene expression data for individual samples, we suggest to distinguish the positive/activator and negative/repressor role of every gene product in each pathway. We show that the relative importance of each gene product in a pathway can be assessed using kinetic models for "low-level" protein interactions. Although the importance factors for the pathway members cannot be so far established for most of the signaling pathways due to the lack of the required experimental data, we showed that ignoring these factors can be sometimes acceptable and that the simplified formula for SPA evaluation may be applied for many cases. We hope that due to its universal applicability, the method OncoFinder will be widely used by the researcher community.
引用
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页数:4
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共 21 条
  • [1] Ongoing and future developments at the Universal Protein Resource
    Apweiler, Rolf
    Martin, Maria Jesus
    O'Donovan, Claire
    Magrane, Michele
    Alam-Faruque, Yasmin
    Antunes, Ricardo
    Barrell, Daniel
    Bely, Benoit
    Bingley, Mark
    Binns, David
    Bower, Lawrence
    Browne, Paul
    Chan, Wei Mun
    Dimmer, Emily
    Eberhardt, Ruth
    Fazzini, Francesco
    Fedotov, Alexander
    Foulger, Rebecca
    Garavelli, John
    Castro, Leyla Garcia
    Huntley, Rachael
    Jacobsen, Julius
    Kleen, Michael
    Laiho, Kati
    Legge, Duncan
    Lin, Quan
    Liu, Wudong
    Luo, Jie
    Orchard, Sandra
    Patient, Samuel
    Pichler, Klemens
    Poggioli, Diego
    Pontikos, Nikolas
    Pruess, Manuela
    Rosanoff, Steven
    Sawford, Tony
    Sehra, Harminder
    Turner, Edward
    Corbett, Matt
    Donnelly, Mike
    van Rensburg, Pieter
    Xenarios, Ioannis
    Bougueleret, Lydie
    Auchincloss, Andrea
    Argoud-Puy, Ghislaine
    Axelsen, Kristian
    Bairoch, Amos
    Baratin, Delphine
    Blatter, Marie-Claude
    Boeckmann, Brigitte
    [J]. NUCLEIC ACIDS RESEARCH, 2011, 39 : D214 - D219
  • [2] Pathway databases and tools for their exploitation: benefits, current limitations and challenges
    Bauer-Mehren, Anna
    Furlong, Laura I.
    Sanz, Ferran
    [J]. MOLECULAR SYSTEMS BIOLOGY, 2009, 5
  • [3] Ligand-dependent responses of the ErbB signaling network: experimental and modeling analyses
    Birtwistle, Marc R.
    Hatakeyama, Mariko
    Yumoto, Noriko
    Ogunnaike, Babatunde A.
    Hoek, Jan B.
    Kholodenko, Boris N.
    [J]. MOLECULAR SYSTEMS BIOLOGY, 2007, 3 (1)
  • [4] Domain-oriented reduction of rule-based network models
    Borisov, N. M.
    Chistopolsky, A. S.
    Faeder, J. R.
    Kholodenko, B. N.
    [J]. IET SYSTEMS BIOLOGY, 2008, 2 (05) : 342 - 351
  • [5] Systems-level interactions between insulin-EGF networks amplify mitogenic signaling
    Borisov, Nikolay
    Aksamitiene, Edita
    Kiyatkin, Anatoly
    Legewie, Stefan
    Berkhout, Jan
    Maiwald, Thomas
    Kaimachnikov, Nikolai P.
    Timmer, Jens
    Hoek, Jan B.
    Kholodenko, Boris N.
    [J]. MOLECULAR SYSTEMS BIOLOGY, 2009, 5
  • [6] Trading the micro-world of combinatorial complexity for the macro-world of protein interaction domains
    Borisov, NM
    Markevich, NI
    Hoek, JB
    Kholodenko, BN
    [J]. BIOSYSTEMS, 2006, 83 (2-3) : 152 - 166
  • [7] A domain-oriented approach to the reduction of combinatorial complexity in signal transduction networks
    Conzelmann, H
    Saez-Rodriguez, J
    Sauter, T
    Kholodenko, BN
    Gilles, ED
    [J]. BMC BIOINFORMATICS, 2006, 7 (1)
  • [8] Sloppiness, robustness, and evolvability in systems biology
    Daniels, Bryan C.
    Chen, Yan-Jiun
    Sethna, James P.
    Gutenkunst, Ryan N.
    Myers, Christopher R.
    [J]. CURRENT OPINION IN BIOTECHNOLOGY, 2008, 19 (04) : 389 - 395
  • [9] SPIKE - a database, visualization and analysis tool of cellular signaling pathways
    Elkon, Ran
    Vesterman, Rita
    Amit, Nira
    Ulitsky, Igor
    Zohar, Idan
    Weisz, Mali
    Mass, Gilad
    Orlev, Nir
    Sternberg, Giora
    Blekhman, Ran
    Assa, Jackie
    Shiloh, Yosef
    Shamir, Ron
    [J]. BMC BIOINFORMATICS, 2008, 9 (1)
  • [10] Haw Robin, 2012, Curr Protoc Bioinformatics, VChapter 8, DOI 10.1002/0471250953.bi0807s38