Implementing and evaluating a Gaussian mixture framework for identifying gene function from TnSeq data

Pac Symp Biocomput. 2019:24:172-183.

Abstract

The rapid acceleration of microbial genome sequencing increases opportunities to understand bacterial gene function. Unfortunately, only a small proportion of genes have been studied. Recently, TnSeq has been proposed as a cost-effective, highly reliable approach to predict gene functions as a response to changes in a cell's fitness before-after genomic changes. However, major questions remain about how to best determine whether an observed quantitative change in fitness represents a meaningful change. To address the limitation, we develop a Gaussian mixture model framework for classifying gene function from TnSeq experiments. In order to implement the mixture model, we present the Expectation-Maximization algorithm and a hierarchical Bayesian model sampled using Stan's Hamiltonian Monte-Carlo sampler. We compare these implementations against the frequentist method used in current TnSeq literature. From simulations and real data produced by E.coli TnSeq experiments, we show that the Bayesian implementation of the Gaussian mixture framework provides the most consistent classification results.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Algorithms
  • Bayes Theorem
  • Computational Biology / methods
  • Computer Simulation
  • DNA Transposable Elements
  • Escherichia coli / genetics
  • Genome, Bacterial*
  • High-Throughput Nucleotide Sequencing
  • Models, Genetic*
  • Models, Statistical
  • Monte Carlo Method
  • Mutagenesis, Insertional
  • Normal Distribution

Substances

  • DNA Transposable Elements