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Updated: Apr 22, 2026

Targeted RNA Sequencing Assay to Characterize Gene Expression and Genomic Alterations
Published on: August 4, 2016
Gene expression profiling for targeted cancer treatment
1Elsevier, Inc. , 5635 Fishers Lane, Rockville, MD 20852 USA a.yuryev@elsevier.com.
Introduction:
There is certain degree of frustration and discontent in the area of microarray gene expression data analysis of cancer datasets. It arises from the mathematical problem called 'curse of dimensionality,' which is due to the small number of samples available in training sets, used for calculating transcriptional signatures from the large number of differentially expressed (DE) genes, measured by microarrays. The new generation of causal reasoning algorithms can provide solutions to the curse of dimensionality by transforming microarray data into activity of a small number of cancer hallmark pathways. This new approach can make feature space dimensionality optimal for mathematical signature calculations.
Areas Covered:
The author reviews the reasons behind the current frustration with transcriptional signatures derived from DE genes in cancer. He also provides an overview of the novel methods for signature calculations based on differentially variable genes and expression regulators. Furthermore, the authors provide perspectives on causal reasoning algorithms that use prior knowledge about regulatory events described in scientific literature to identify expression regulators responsible for the differential expression observed in cancer samples.
Expert Opinion:
The author advocates causal reasoning methods to calculate cancer pathway activity signatures. The current challenge for these algorithms is in ensuring quality of the knowledgebase. Indeed, the development of cancer hallmark pathway collections, together with statistical algorithms to transform activity of expression regulators into pathway activity, are necessary for causal reasoning to be used in cancer research.
Insights
Causal reasoning algorithms offer a solution to the curse of dimensionality in cancer gene expression analysis. This approach transforms microarray data into cancer pathway activity, optimizing signature calculations.
Area of Science:
- Bioinformatics
- Computational Biology
- Cancer Research
Background:
- Microarray gene expression data analysis in cancer is hampered by the 'curse of dimensionality'.
- This arises from limited sample sizes in training sets for calculating transcriptional signatures from numerous differentially expressed genes.
- Existing methods face challenges in accurately identifying cancer-related gene expression patterns.
Purpose of the Study:
- To address the limitations of current microarray data analysis in cancer research.
- To introduce causal reasoning algorithms as a novel approach for analyzing gene expression data.
- To optimize the calculation of transcriptional signatures by reducing data dimensionality.
Main Methods:
- Reviewing current frustrations with transcriptional signatures derived from differentially expressed genes.
- Overviewing novel signature calculation methods using differentially variable genes and expression regulators.
- Exploring causal reasoning algorithms that leverage prior knowledge of regulatory events.
Main Results:
- Causal reasoning algorithms can transform high-dimensional microarray data into the activity of a limited number of cancer hallmark pathways.
- This transformation optimizes feature space dimensionality for accurate mathematical signature calculations.
- Identifies expression regulators responsible for differential expression in cancer samples.
Conclusions:
- Advocates for the use of causal reasoning methods to calculate cancer pathway activity signatures.
- Highlights the need for high-quality knowledgebases and statistical algorithms for transforming expression regulator activity into pathway activity.
- Emphasizes the potential of causal reasoning for advancing cancer research.
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