Integration of multi-omics data for prediction of phenotypic traits using random forest.
BACKGROUND
In order to find genetic and metabolic pathways related to phenotypic traits of interest, we analyzed gene expression data, metabolite data obtained with GC-MS and LC-MS, proteomics data and a selected set of tuber quality phenotypic data from a diploid segregating mapping population of potato. In this study we present an approach to integrate these ~ omics data sets for the purpose of predicting phenotypic traits. This gives us networks of relatively small sets of interrelated ~ omics variables that can predict, with higher accuracy, a quality trait of interest.


RESULTS
We used Random Forest regression for integrating multiple ~ omics data for prediction of four quality traits of potato: tuber flesh colour, DSC onset, tuber shape and enzymatic discoloration. For tuber flesh colour beta-carotene hydroxylase and zeaxanthin epoxidase were ranked first and forty-fourth respectively both of which have previously been associated with flesh colour in potato tubers. Combining all the significant genes, LC-peaks, GC-peaks and proteins, the variation explained was 75 %, only slightly more than what gene expression or LC-MS data explain by themselves which indicates that there are correlations among the variables across data sets. For tuber shape regressed on the gene expression, LC-MS, GC-MS and proteomics data sets separately, only gene expression data was found to explain significant variation. For DSC onset, we found 12 significant gene expression, 5 metabolite levels (GC) and 2 proteins that are associated with the trait. Using those 19 significant variables, the variation explained was 45 %. Expression QTL (eQTL) analyses showed many associations with genomic regions in chromosome 2 with also the highest explained variation compared to other chromosomes. Transcriptomics and metabolomics analysis on enzymatic discoloration after 5 min resulted in 420 significant genes and 8 significant LC metabolites, among which two were putatively identified as caffeoylquinic acid methyl ester and tyrosine.


CONCLUSIONS
In this study, we made a strategy for selecting and integrating multiple ~ omics data using random forest method and selected representative individual peaks for networks based on eQTL, mQTL or pQTL information. Network analysis was done to interpret how a particular trait is associated with gene expression, metabolite and protein data.
Wageningen UR Plant Breeding, Wageningen University & Research Centre, PO Box 6700 AJ, Wageningen, The Netherlands.|MRC Human Nutrition Research, 120 Fulbourn Road, Cambridge, CB1 9NL, UK.
Animesh
A
Acharjee
Wageningen UR Plant Breeding, Wageningen University & Research Centre, PO Box 6700 AJ, Wageningen, The Netherlands.|Keygene NV, PO Box 216, 6700 AE, Wageningen, The Netherlands.
Bjorn
B
Kloosterman
Wageningen UR Plant Breeding, Wageningen University & Research Centre, PO Box 6700 AJ, Wageningen, The Netherlands.
Richard G F
RG
Visser
Wageningen UR Plant Breeding, Wageningen University & Research Centre, PO Box 6700 AJ, Wageningen, The Netherlands. chris.maliepaard@wur.nl.
Chris
C
Maliepaard
D002851:Chromatography, High Pressure Liquid; D032461:Chromosomes, Plant / Q000235:genetics / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D018506:Gene Expression Regulation, Plant; D023281:Genomics; D013058:Mass Spectrometry; D055432:Metabolomics; D010641:Phenotype; D010940:Plant Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D035281:Plant Tubers / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D040641:Quantitative Trait Loci; D011198:Solanum tuberosum / Q000235:genetics / Q000378:metabolism*
D010940:Plant Proteins
Data integration; Genetical genomics; Networks; Random forest