title: The OncoFinder algorithm for minimizing the errors introduced by the high-throughput methods of transcriptome analysis.
abstract: The diversity of the installed sequencing and microarray equipment make it increasingly difficult to compare and analyze the gene expression datasets obtained using the different methods. Many applications requiring high-quality and low error rates cannot make use of available data using traditional analytical approaches. Recently, we proposed a new concept of signalome-wide analysis of functional changes in the intracellular pathways termed OncoFinder, a bioinformatic tool for quantitative estimation of the signaling pathway activation (SPA). We also developed methods to compare the gene expression data obtained using multiple platforms and minimizing the error rates by mapping the gene expression data onto the known and custom signaling pathways. This technique for the first time makes it possible to analyze the functional features of intracellular regulation on a mathematical basis. In this study we show that the OncoFinder method significantly reduces the errors introduced by transcriptome-wide experimental techniques. We compared the gene expression data for the same biological samples obtained by both the next generation sequencing (NGS) and microarray methods. For these different techniques we demonstrate that there is virtually no correlation between the gene expression values for all datasets analyzed (R (2) < 0.1). In contrast, when the OncoFinder algorithm is applied to the data we observed clear-cut correlations between the NGS and microarray gene expression datasets. The SPA profiles obtained using NGS and microarray techniques were almost identical for the same biological samples allowing for the platform-agnostic analytical applications. We conclude that this feature of the OncoFinder enables to characterize the functional states of the transcriptomes and interactomes more accurately as before, which makes OncoFinder a method of choice for many applications including genetics, physiology, biomedicine, and molecular diagnostics.
authors.affiliation: Group for Genomic Regulation of Cell Signaling Systems, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences Moscow, Russia ; Laboratory of Bioinformatics, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology Moscow, Russia ; Pathway Pharmaceuticals Wan Chai, Hong Kong.
authors.forename: Anton A
authors.initials: AA
authors.lastname: Buzdin
authors.affiliation: Laboratory of Bioinformatics, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology Moscow, Russia ; Pathway Pharmaceuticals Wan Chai, Hong Kong.
authors.forename: Alex A
authors.initials: AA
authors.lastname: Zhavoronkov
authors.affiliation: Pathway Pharmaceuticals Wan Chai, Hong Kong ; Laboratory of Systems Biology, A.I. Burnasyan Federal Medical Biophysical Center Moscow, Russia.
authors.forename: Mikhail B
authors.initials: MB
authors.lastname: Korzinkin
authors.affiliation: Laboratory of Bioinformatics, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology Moscow, Russia.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Roumiantsev
authors.affiliation: Laboratory of Bioinformatics, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology Moscow, Russia ; Pathway Pharmaceuticals Wan Chai, Hong Kong.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Aliper
authors.affiliation: Pathway Pharmaceuticals Wan Chai, Hong Kong ; Laboratory of Systems Biology, A.I. Burnasyan Federal Medical Biophysical Center Moscow, Russia.
authors.forename: Larisa S
authors.initials: LS
authors.lastname: Venkova
authors.affiliation: Pathway Pharmaceuticals Wan Chai, Hong Kong ; Laboratory of Systems Biology, A.I. Burnasyan Federal Medical Biophysical Center Moscow, Russia.
authors.forename: Philip Y
authors.initials: PY
authors.lastname: Smirnov
authors.affiliation: Pathway Pharmaceuticals Wan Chai, Hong Kong ; Laboratory of Systems Biology, A.I. Burnasyan Federal Medical Biophysical Center Moscow, Russia.
authors.forename: Nikolay M
authors.initials: NM
authors.lastname: Borisov
keywords: RNA-Seq; correction of errors; gene expression; intracellular signaling pathway activation; microarray hybridization; next generation sequencing; signalome; transcriptome profiling