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The OncoFinder algorithm for minimizing the errors introduced by the high-throughput methods of transcriptome
Anton A Buzdin1, Alex A Zhavoronkov2, Mikhail B Korzinkin3
1Group 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.
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.
Insights
Comparing gene expression data from different platforms is challenging. OncoFinder, a novel bioinformatic tool, enables accurate, platform-agnostic analysis of signaling pathway activation (SPA) by reducing errors in gene expression datasets.
Area of Science:
- Bioinformatics
- Genomics
- Systems Biology
Background:
- Gene expression data from diverse platforms (sequencing, microarrays) are difficult to compare due to inherent variability.
- Traditional analytical methods struggle with high-error, multi-platform gene expression data, limiting downstream applications.
Purpose of the Study:
- To introduce OncoFinder, a bioinformatic tool for quantitative estimation of signaling pathway activation (SPA).
- To demonstrate OncoFinder's ability to enable platform-agnostic comparison of gene expression data, minimizing errors.
- To validate OncoFinder's effectiveness in analyzing intracellular pathway functional changes.
Main Methods:
- Development of OncoFinder, a bioinformatic tool for quantitative SPA estimation.
- Mapping gene expression data onto known and custom signaling pathways to minimize errors.
- Comparative analysis of gene expression datasets from Next-Generation Sequencing (NGS) and microarray platforms for the same biological samples.
Main Results:
- Direct comparison of NGS and microarray datasets showed minimal correlation (R² < 0.1).
- Application of the OncoFinder algorithm revealed strong correlations between NGS and microarray data.
- OncoFinder generated nearly identical SPA profiles for the same samples across different platforms, enabling platform-agnostic analysis.
Conclusions:
- OncoFinder significantly reduces errors in transcriptome-wide experimental techniques.
- The platform-agnostic nature of OncoFinder allows for more accurate characterization of transcriptome and interactome functional states.
- OncoFinder is a valuable tool for genetics, physiology, biomedicine, and molecular diagnostics.
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