Integrating data to understand gene/environment interactions under different dietary regimens

Charles Darwin
15th November 2016

Organism

Caenorhabditis elegans
12 strains collected around the world

Caenorhabditis elegans

Organism: genome

\includegraphics[width=0.5]{input/images/bar/chromSizes.pdf} Chromosome sizes

Origin of strains

Cities of origin of the nematode strains

Data

Whole genome
RNA
Metabolome (mass spectrometry)
Behaviour and life history traits

Effect of diet on C. elegans

Abundance of food influences locomotion
Higher reproductive fitness when grown on C. arvensicola than when grown on E. coli
Extended lifespan when grown on Bacillus mycoides or Bacillus soli

Question

What are the pathways involved in mediating the effect of diet on the nematode's phenotype?

Experimental design

Genetic association study

What is the genetic basis of the nematode's phenotype? Phenotypes under consideration:

transcriptome
metabolome
locomotion
fat content
lifespan

Genetic association studies

A lot of research on genetic/single phenotype association, but not much that combines different data layers.

The power of genetic variation

Can we gain insight in into the biology of a species by studying more than one genotype? If strains cluster along replicates, then it must be genetics that explains this variation. PCA on gene expression

Data integration

Can we gain more insight into molecular pathways underlying a phenotype by integrating different layers of data?

Interaction between the genotype and the environment

Are the effects of diet the same for each strain?