title: Pheno2Geno - High-throughput generation of genetic markers and maps from molecular phenotypes for crosses between inbred strains.
abstract: BACKGROUND
  Genetic markers and maps are instrumental in quantitative trait locus (QTL) mapping in segregating populations. The resolution of QTL localization depends on the number of informative recombinations in the population and how well they are tagged by markers. Larger populations and denser marker maps are better for detecting and locating QTLs. Marker maps that are initially too sparse can be saturated or derived de novo from high-throughput omics data, (e.g. gene expression, protein or metabolite abundance). If these molecular phenotypes are affected by genetic variation due to a major QTL they will show a clear multimodal distribution. Using this information, phenotypes can be converted into genetic markers.
  
  
  RESULTS
  The Pheno2Geno tool uses mixture modeling to select phenotypes and transform them into genetic markers suitable for construction and/or saturation of a genetic map. Pheno2Geno excludes candidate genetic markers that show evidence for multiple possibly epistatically interacting QTL and/or interaction with the environment, in order to provide a set of robust markers for follow-up QTL mapping. We demonstrate the use of Pheno2Geno on gene expression data of 370,000 probes in 148 A. thaliana recombinant inbred lines. Pheno2Geno is able to saturate the existing genetic map, decreasing the average distance between markers from 7.1 cM to 0.89 cM, close to the theoretical limit of 0.68 cM (with 148 individuals we expect a recombination every 100/148=0.68 cM); this pinpointed almost all of the informative recombinations in the population.
  
  
  CONCLUSIONS
  The Pheno2Geno package makes use of genome-wide molecular profiling and provides a tool for high-throughput de novo map construction and saturation of existing genetic maps. Processing of the showcase dataset takes less than 30 minutes on an average desktop PC. Pheno2Geno improves QTL mapping results at no additional laboratory cost and with minimum computational effort. Its results are formatted for direct use in R/qtl, the leading R package for QTL studies. Pheno2Geno is freely available on CRAN under "GNU GPL v3". The Pheno2Geno package as well as the tutorial can also be found at: http://pheno2geno.nl .
authors.affiliation: University of Groningen, Groningen Bioinformatics Centre, Nijenborgh 7, Groningen, 9747, AG, The Netherlands. konradzych2@gmail.com.|Jagiellonian University, Faculty of Biochemistry, Biophysics and Biotechnology, Gronostajowa Street 7, Krakow, 30-387, Poland. konradzych2@gmail.com.
authors.forename: Konrad
authors.initials: K
authors.lastname: Zych
authors.affiliation: University of Groningen, Groningen Bioinformatics Centre, Nijenborgh 7, Groningen, 9747, AG, The Netherlands. yang.li@rug.nl.|University of Groningen, University Medical Center Groningen, Department of Genetics, PO Box 30001, Groningen, 9700, RB, The Netherlands. yang.li@rug.nl.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: University of Groningen, University Medical Center Groningen, Genomics Coordination Center, PO Box 30001, Groningen, 9700, RB, The Netherlands. k.j.van.der.velde@umcg.nl.
authors.forename: Joeri K
authors.initials: JK
authors.lastname: van der Velde
authors.affiliation: Wageningen University, Wageningen Seed Lab, Droevendaalsesteeg 1, Wageningen, The Netherlands. rvl.joosen@gmail.com.
authors.forename: Ronny V L
authors.initials: RV
authors.lastname: Joosen
authors.affiliation: Wageningen University, Wageningen Seed Lab, Droevendaalsesteeg 1, Wageningen, The Netherlands. wilco.ligterink@wur.nl.
authors.forename: Wilco
authors.initials: W
authors.lastname: Ligterink
authors.affiliation: University of Groningen, Groningen Bioinformatics Centre, Nijenborgh 7, Groningen, 9747, AG, The Netherlands. r.c.jansen@rug.nl.
authors.forename: Ritsert C
authors.initials: RC
authors.lastname: Jansen
authors.affiliation: University of Groningen, Groningen Bioinformatics Centre, Nijenborgh 7, Groningen, 9747, AG, The Netherlands. danny.arends@gmail.com.
authors.forename: Danny
authors.initials: D
authors.lastname: Arends
mesh_terms: D017360:Arabidopsis / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods; D003433:Crosses, Genetic; D018744:DNA, Plant / Q000235:genetics; D008040:Genetic Linkage; D005819:Genetic Markers; D018745:Genome, Plant; D010641:Phenotype; D040641:Quantitative Trait Loci
chemical_list: D018744:DNA, Plant; D005819:Genetic Markers