Switched Latent Force Models for Reverse-Engineering Transcriptional Regulation in Gene Expression Data

Andres F. Lopez-Lopera, Mauricio A. Alvarez

Research output: Contribution to journalArticlepeer-review

Abstract

To survive environmental conditions, cells transcribe their response activities into encoded mRNA sequences in order to produce certain amounts of protein concentrations. The external conditions are mapped into the cell through the activation of special proteins called transcription factors (TFs). Due to the difficult task to measure experimentally TF behaviors, and the challenges to capture their quick-time dynamics, different types of models based on differential equations have been proposed. However, those approaches usually incur in costly procedures, and they present problems to describe sudden changes in TF regulators. In this paper, we present a switched dynamical latent force model for reverse-engineering transcriptional regulation in gene expression data which allows the exact inference over latent TF activities driving some observed gene expressions through a linear differential equation. To deal with discontinuities in the dynamics, we introduce an approach that switches between different TF activities and different dynamical systems. This creates a versatile representation of transcription networks that can capture discrete changes and non-linearities. We evaluate our model on both simulated data and real data (e.g., microaerobic shift in E. coli, yeast respiration), concluding that our framework allows for the fitting of the expression data while being able to infer continuous-time TF profiles.

Original languageEnglish
Article number8078278
Pages (from-to)322-335
Number of pages14
JournalIEEE/ACM Transactions on Computational Biology and Bioinformatics
Volume16
Issue number1
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • Biology and genetics
  • differential equations
  • gene expression data
  • latent force models
  • reverse-engineering
  • transcriptional regulation

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