An integrative approach for building personalized gene regulatory networks for precision medicine

Monique G. P. van der Wijst, Dylan H. de Vries, Harm Brugge, Harm-Jan Westra, Lude Franke*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

59 Citations (Scopus)
528 Downloads (Pure)

Abstract

Only a small fraction of patients respond to the drug prescribed to treat their disease, which means that most are at risk of unnecessary exposure to side effects through ineffective drugs. This inter-individual variation in drug response is driven by differences in gene interactions caused by each patient's genetic background, environmental exposures, and the proportions of specific cell types involved in disease. These gene interactions can now be captured by building gene regulatory networks, by taking advantage of RNA velocity (the time derivative of the gene expression state), the ability to study hundreds of thousands of cells simultaneously, and the falling price of single-cell sequencing. Here, we propose an integrative approach that leverages these recent advances in single-cell data with the sensitivity of bulk data to enable the reconstruction of personalized, cell-type- and context-specific gene regulatory networks. We expect this approach will allow the prioritization of key driver genes for specific diseases and will provide knowledge that opens new avenues towards improved personalized healthcare.

Original languageEnglish
Article number96
Number of pages15
JournalGenome medicine
Volume10
DOIs
Publication statusPublished - 19-Dec-2018

Keywords

  • SINGLE-CELL
  • RNA-SEQ
  • EXPRESSION
  • INFERENCE
  • TIME
  • VARIANTS
  • IDENTIFICATION
  • CIRCUITS
  • TRANSCRIPTION
  • ENCYCLOPEDIA

Fingerprint

Dive into the research topics of 'An integrative approach for building personalized gene regulatory networks for precision medicine'. Together they form a unique fingerprint.

Cite this