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RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
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Using shRNA experiments to validate gene regulatory networks.

Catharina Olsen1, Kathleen Fleming2, Niall Prendergast2

  • 1Machine Learning Group, Université Libre de Bruxelles, Brussels, Belgium ; Interuniversity Institute of Bioinformatics in Brussels (IB) , Belgium.

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|October 21, 2015
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Summary
This summary is machine-generated.

Gene regulatory network (GRN) validation is challenging. This study presents a data-driven method using gene knock-down experiments for quantitative GRN assessment and comparison of inference techniques.

Keywords:
Colon cancerGene expressionKnock-downMicroarrayshRNA

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Area of Science:

  • Systems Biology
  • Bioinformatics
  • Genomics

Background:

  • Quantitative validation of gene regulatory networks (GRNs) from observational expression data is typically complex and resource-intensive.
  • Existing methods often rely on time-consuming and expensive laboratory experiments.
  • A significant challenge in the field has been the statistical comparison of different network inference techniques.

Purpose of the Study:

  • To present a purely data-driven framework for the quantitative validation of large-scale gene regulatory networks.
  • To enable the statistical comparison of multiple network inference methods.
  • To provide access to gene expression data and analysis code for reproducibility.

Main Methods:

  • Utilizing gene knock-down experiments for quantitative assessment of GRNs.
  • Developing a data-driven approach to bypass traditional experimental validation bottlenecks.
  • Employing R code for data access and analysis reproduction.

Main Results:

  • Demonstrated that gene knock-down experiments can quantitatively assess GRN quality.
  • Established a framework for statistically comparing various network inference techniques.
  • Detailed the gene expression data (GSE53091) and quality control measures.

Conclusions:

  • A novel, data-driven validation framework for gene regulatory networks has been established.
  • The proposed method facilitates quantitative assessment and comparative analysis of GRN inference.
  • The associated data and code are publicly available to support further research.