McEnhancer: predicting gene expression via semi-supervised assignment of enhancers to target genes.

Journal: Genome biology
PMID:

Abstract

Transcriptional enhancers regulate spatio-temporal gene expression. While genomic assays can identify putative enhancers en masse, assigning target genes is a complex challenge. We devised a machine learning approach, McEnhancer, which links target genes to putative enhancers via a semi-supervised learning algorithm that predicts gene expression patterns based on enriched sequence features. Predicted expression patterns were 73-98% accurate, predicted assignments showed strong Hi-C interaction enrichment, enhancer-associated histone modifications were evident, and known functional motifs were recovered. Our model provides a general framework to link globally identified enhancers to targets and contributes to deciphering the regulatory genome.

Authors

  • Dina Hafez
    Department of Computer Science, Duke University, Durham, 27708, NC, USA.
  • Aslihan Karabacak
    Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, 13125, Germany.
  • Sabrina Krueger
    Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, 13125, Germany.
  • Yih-Chii Hwang
    Genomics and Computational Biology Graduate Program, University of Pennsylvania, Philadelphia, 19104, PA, USA.
  • Li-San Wang
    Genomics and Computational Biology Graduate Program, University of Pennsylvania, Philadelphia, 19104, PA, USA.
  • Robert P Zinzen
    Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, 13125, Germany. Robert.Zinzen@mdc-berlin.de.
  • Uwe Ohler
    Department of Biology, Humboldt Universität zu Berlin, 10117 Berlin, Germany; The Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, 10115 Berlin, Germany; Department of Computer Science, Humboldt Universität zu Berlin, 10117 Berlin, Germany. Electronic address: uwe.ohler@mdc-berlin.de.