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08.09.18 Branching gene expression in response to infection analysed with Gaussian processes

last modified Oct 09, 2018 05:12 PM
Penfold et al from the Surani lab apply statistical methods to understand patterns in changes in gene expression following perturbations such as infection
08.09.18 Branching gene expression in response to infection analysed with Gaussian processes

Fig. 1 (extract): Fitting a branching process with different Gaussian processes

Branch-recombinant Gaussian processes for analysis of perturbations in biological time series

Penfold CA et al. (2018) Bioinformatics Volume 34, Issue 17, pp i1005–i1013. DOI: 10.1093/bioinformatics/bty603

 

Abstract from the paper

Motivation

A common class of behaviour encountered in the biological sciences involves branching and recombination. During branching, a statistical process bifurcates resulting in two or more potentially correlated processes that may undergo further branching; the contrary is true during recombination, where two or more statistical processes converge. A key objective is to identify the time of this bifurcation (branch or recombination time) from time series measurements, e.g. by comparing a control time series with perturbed time series. Gaussian processes (GPs) represent an ideal framework for such analysis, allowing for nonlinear regression that includes a rigorous treatment of uncertainty. Currently, however, GP models only exist for two-branch systems. Here, we highlight how arbitrarily complex branching processes can be built using the correct composition of covariance functions within a GP framework, thus outlining a general framework for the treatment of branching and recombination in the form of branch-recombinant Gaussian processes (B-RGPs).

Results

We first benchmark the performance of B-RGPs compared to a variety of existing regression approaches, and demonstrate robustness to model misspecification. B-RGPs are then used to investigate the branching patterns of Arabidopsis thaliana gene expression following inoculation with the hemibotrophic bacteria, Pseudomonas syringae DC3000, and a disarmed mutant strain, hrpA. By grouping genes according to the number of branches, we could naturally separate out genes involved in basal immune response from those subverted by the virulent strain, and show enrichment for targets of pathogen protein effectors. Finally, we identify two early branching genes WRKY11 and WRKY17, and show that genes that branched at similar times to WRKY11/17 were enriched for W-box binding motifs, and overrepresented for genes differentially expressed in WRKY11/17 knockouts, suggesting that branch time could be used for identifying direct and indirect binding targets of key transcription factors.

Availability and implementation

https://github.com/cap76/BranchingGPs

Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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