Machine learning-based differential network analysis: A study of stress-responsive transcriptomes in Arabidopsis

Chuang Ma, Mingming Xin, Kenneth A. Feldmann, Xiangfeng Wang

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Machine learning (ML) is an intelligent data mining technique that builds a prediction model based on the learning of prior knowledge to recognize patterns in large-scale data sets. We present an ML-based methodology for transcriptome analysis via comparison of gene coexpression networks, implemented as an R package called machine learning-based differential network analysis (mlDNA) and apply this method to reanalyze a set of abiotic stress expression data in Arabidopsis thaliana. The mlDNA first used a ML-based filtering process to remove nonexpressed, constitutively expressed, or non-stressresponsive "noninformative" genes prior to network construction, through learning the patterns of 32 expression characteristics of known stress-related genes. The retained "informative" genes were subsequently analyzed by ML-based network comparison to predict candidate stress-related genes showing expression and network differences between control and stress networks, based on 33 network topological characteristics. Comparative evaluation of the network-centric and gene-centric analytic methods showed that mlDNA substantially outperformed traditional statistical testing-based differential expression analysis at identifying stress-related genes, with markedly improved prediction accuracy. To experimentally validate the mlDNA predictions, we selected 89 candidates out of the 1784 predicted salt stress-related genes with available SALK T-DNA mutagenesis lines for phenotypic screening and identified two previously unreported genes, mutants of which showed salt-sensitive phenotypes.

Original languageEnglish (US)
Pages (from-to)520-537
Number of pages18
JournalPlant Cell
Volume26
Issue number2
DOIs
StatePublished - Feb 2014

ASJC Scopus subject areas

  • Plant Science
  • Cell Biology

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