RT Journal Article
SR Electronic
T1 Assigning function to natural allelic variation via dynamic modeling of gene network induction
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 140467
DO 10.1101/140467
A1 Magali Richard
A1 Florent Chuffart
A1 Hélène Duplus-Bottin
A1 Fanny Pouyet
A1 Martin Spichty
A1 Etienne Fulcrand
A1 Marianne Entrevan
A1 Audrey Barthelaix
A1 Michael Springer
A1 Daniel Jost
A1 Gaёl Yvert
YR 2017
UL http://biorxiv.org/content/early/2017/05/20/140467.abstract
AB More and more natural DNA variants are being linked to physiological traits. Yet, understanding what differences they make on molecular regulations remains challenging. Important properties of gene regulatory networks can be captured by computational models. If model parameters can be ‘personalized’ according to the genotype, their variation may then reveal how DNA variants operate in the network. Here, we combined experiments and computations to visualize natural alleles of the yeast GAL3 gene in a space of model parameters describing the galactose response network. Alleles altering the activation of Gal3p by galactose were discriminated from those affecting its activity (production/degradation or efficiency of the activated protein). The approach allowed us to correctly predict that a non-synonymous SNP would change the binding affinity of Gal3p with the Gal80p transcriptional repressor. Our results illustrate how personalizing gene regulatory models can be used for the mechanistic interpretation of genetic variants.