A MapReduce tool for in-depth analysis of KEGG pathways: identification and visualization of therapeutic target candidates

Intracellular biochemical reactions emerge from the interaction among multiple extracellular signaling components. Considering the number, type and connections of the signaling components represents a needed step to characterize, identify and describe potential targets for a clinical purpose. However, it is increasingly documented that the presence of sub-types of signaling proteins, branching and crosstalk may lead to very variable outcomes in the same path, which is not always well defined experimentally. For this reason, we present an improved version of the algorithm based on the MapReduce paradigm to facilitate the discovery of new therapeutic targets. Our algorithm allows you to scan and perform a search in depth of biological pathway in order to analyze less recurrent and therefore non-trivial paths. These routes represent a chain of biochemical interactions among different biological actors that can be represented by quite distant nodes along the pathway. This type of analysis can also be performed manually, but with high execution times due to the large amount of pathways and genes present. Thus, our tool performs exhaustive analysis in an automated way, drastically reducing the time required. Our proposal allows us to discover the genes far from the initial target genes, also showing the number of occurrences of a given path found within the set of biological pathways analyzed during the simulation.

[1]  Christopher J. Rawlings,et al.  Ondex Web: web-based visualization and exploration of heterogeneous biological networks , 2013, Bioinform..

[2]  Davide Heller,et al.  STRING v10: protein–protein interaction networks, integrated over the tree of life , 2014, Nucleic Acids Res..

[3]  Jeffrey Heer,et al.  D³ Data-Driven Documents , 2011, IEEE Transactions on Visualization and Computer Graphics.

[4]  R. Bernards,et al.  Phospho-ERK is a response biomarker to a combination of sorafenib and MEK inhibition in liver cancer , 2018, bioRxiv.

[5]  Joaquín Dopazo,et al.  Web-based network analysis and visualization using CellMaps , 2016, Bioinform..

[6]  Giulia Russo,et al.  Computational modeling reveals MAP3K8 as mediator of resistance to vemurafenib in thyroid cancer stem cells , 2018, Bioinform..

[7]  Maud Martin,et al.  DUSP3/VHR is a pro-angiogenic atypical dual-specificity phosphatase , 2014, Molecular Cancer.

[8]  Jeffrey Heer,et al.  SpanningAspectRatioBank Easing FunctionS ArrayIn ColorIn Date Interpolator MatrixInterpola NumObjecPointI Rectang ISchedu Parallel Pause Scheduler Sequen Transition Transitioner Transiti Tween Co DelimGraphMLCon IData JSONCon DataField DataSc Dat DataSource Data DataUtil DirtySprite LineS RectSprite , 2011 .

[9]  Gary D. Bader,et al.  Cytoscape.js: a graph theory library for visualisation and analysis , 2015, Bioinform..

[10]  Christian Napoli,et al.  A MapReduce Based Tool for the Analysis and Discovery of Novel Therapeutic Targets , 2019, 2019 27th Euromicro International Conference on Parallel, Distributed and Network-Based Processing (PDP).

[11]  Hiroyuki Ogata,et al.  KEGG: Kyoto Encyclopedia of Genes and Genomes , 1999, Nucleic Acids Res..

[12]  C. Cloninger,et al.  mTORC2 modulates feedback regulation of p38 MAPK activity via DUSP10/MKP5 to confer differential responses to PP242 in glioblastoma , 2014, Genes & cancer.