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Bioinformatics Meets Biomedicine: OncoFinder, a Quantitative Approach for Interrogating Molecular Pathways Using Gene Expression Data

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Biological Networks and Pathway Analysis

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1613))

Abstract

We propose a biomathematical approach termed OncoFinder (OF) that enables performing both quantitative and qualitative analyses of the intracellular molecular pathway activation. OF utilizes an algorithm that distinguishes the activator/repressor role of every gene product in a pathway. This method is applicable for the analysis of any physiological, stress, malignancy, and other conditions at the molecular level. OF showed a strong potential to neutralize background-caused differences between experimental gene expression data obtained using NGS, microarray and modern proteomics techniques. Importantly, in most cases, pathway activation signatures were better markers of cancer progression compared to the individual gene products. OF also enables correlating pathway activation with the success of anticancer therapy for individual patients. We further expanded this approach to analyze impact of micro RNAs (miRs) on the regulation of cellular interactome. Many alternative sources provide information about miRs and their targets. However, instruments elucidating higher level impact of the established total miR profiles are still largely missing. A variant of OncoFinder termed MiRImpact enables linking miR expression data with its estimated outcome on the regulation of molecular processes, such as signaling, metabolic, cytoskeleton, and DNA repair pathways. MiRImpact was used to establish cancer-specific and cytomegaloviral infection-linked interactomic signatures for hundreds of molecular pathways. Interestingly, the impact of miRs appeared orthogonal to pathway regulation at the mRNA level, which stresses the importance of combining all available levels of gene regulation to build a more objective molecular model of cell.

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Acknowledgments

This work was supported by the Russian Science Foundation grant no. 14-14-01089 (for V.Prassolov and Anton Buzdin), by the Pathway Pharmaceuticals (Hong-Kong) and First Oncology Research and Advisory Center (Russia) Joint Research Initiative and by the Program of the Presidium of the Russian Academy of Sciences “Dynamics and Conservation of Genomes” (for Nikolay Borisov and Alex Zhavoronkov).

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Authors and Affiliations

  1. Pathway Pharmaceuticals, Wan Chai, Hong Kong SAR

    Anton A. Buzdin & Alex A. Zhavoronkov

  2. Centre for Convergence of Nano-, Bio-, Information and Cognitive Sciences and Technologies, National Research Centre “Kurchatov Institute”, Bldg 140, Suite 415, 1, Akademika Kurchatova sq., Moscow, 123182, Russia

    Anton A. Buzdin & Nikolay M. Borisov

  3. Group for Genomic Regulation of Cell Signaling Systems, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, Russia

    Anton A. Buzdin & Alex A. Zhavoronkov

  4. Laboratory of Bioinformatics, D. Rogachev Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia

    Anton A. Buzdin

  5. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova street 32, Mosow, 119991, Russia

    Vladimir Prassolov

  6. Department of Personalized Medicine, First Oncology Research and Advisory Center, Moscow, Russia

    Nikolay M. Borisov

Authors
  1. Anton A. Buzdin
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  2. Vladimir Prassolov
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  3. Alex A. Zhavoronkov
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  4. Nikolay M. Borisov
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Corresponding author

Correspondence to Anton A. Buzdin .

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Editors and Affiliations

  1. Keck School of Medicine, University of Southern California, Los Angeles, California, USA

    Tatiana V. Tatarinova

  2. Prosapia Genetics, Solana Beach, California, USA

    Yuri Nikolsky

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Buzdin, A.A., Prassolov, V., Zhavoronkov, A.A., Borisov, N.M. (2017). Bioinformatics Meets Biomedicine: OncoFinder, a Quantitative Approach for Interrogating Molecular Pathways Using Gene Expression Data. In: Tatarinova, T., Nikolsky, Y. (eds) Biological Networks and Pathway Analysis. Methods in Molecular Biology, vol 1613. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7027-8_4

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  • DOI: https://doi.org/10.1007/978-1-4939-7027-8_4

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