Since their introduction in the 50's, variance component mixed models have been widely used in many application fields. In this context, ReML estimation is by far the most popular procedure to infer the variance components of the model. Although many implementations of the ReML procedure are readily available, there is still need for computational improvements due to the ever-increasing size of the datasets to be handled, and to the complexity of the models to be adjusted. In this paper, we present a Min-Max (MM) algorithm for ReML inference and combine it with several speed-up procedures. The ReML MM algorithm we present is compared to 5 state-of-the-art publicly available algorithms used in statistical genetics. The computational performance of the different algorithms are evaluated on several datasets representing different plant breeding experimental designs. The MM algorithm ranks among the top 2 methods in almost all settings and is more versatile than many of its competitors. The MM algorithm is a promising alternative to the classical AI-ReML algorithm in the context of variance component mixed models. It is available in the MM4LMM R-package.

SUMMARY: Compilation of genetic maps combined to quantitative trait loci (QTL) meta-analysis has proven to be a powerful approach contributing to the identification of candidate genes underlying quantitative traits. BioMercator was the first software offering a complete set of algorithms and visualization tool covering all steps required to perform QTL meta-analysis. Despite several limitations, the software is still widely used. We developed a new version proposing additional up to date methods and improving graphical representation and exploration of large datasets. AVAILABILITY AND IMPLEMENTATION: BioMercator V3 is implemented in JAVA and freely available (http://moulon.inra.fr/biomercator) CONTACT: [email protected].

BACKGROUND: Integration of multiple results from Quantitative Trait Loci (QTL) studies is a key point to understand the genetic determinism of complex traits. Up to now many efforts have been made by public database developers to facilitate the storage, compilation and visualization of multiple QTL mapping experiment results. However, studying the congruency between these results still remains a complex task. Presently, the few computational and statistical frameworks to do so are mainly based on empirical methods (e.g. consensus genetic maps are generally built by iterative projection). RESULTS: In this article, we present a new computational and statistical package, called MetaQTL, for carrying out whole-genome meta-analysis of QTL mapping experiments. Contrary to existing methods, MetaQTL offers a complete statistical process to establish a consensus model for both the marker and the QTL positions on the whole genome. First, MetaQTL implements a new statistical approach to merge multiple distinct genetic maps into a single consensus map which is optimal in terms of weighted least squares and can be used to investigate recombination rate heterogeneity between studies. Secondly, assuming that QTL can be projected on the consensus map, MetaQTL offers a new clustering approach based on a Gaussian mixture model to decide how many QTL underly the distribution of the observed QTL. CONCLUSION: We demonstrate using simulations that the usual model choice criteria from mixture model literature perform relatively well in this context. As expected, simulations also show that this new clustering algorithm leads to a reduction in the length of the confidence interval of QTL location provided that across studies there are enough observed QTL for each underlying true QTL location. The usefulness of our approach is illustrated on published QTL detection results of flowering time in maize. Finally, MetaQTL is freely available at http://bioinformatics.org/mqtl.

SUMMARY: Breeding programs face the challenge of integrating information from genomics and from quantitative trait loci (QTL) analysis in order to identify genomic sequences controlling the variation of important traits. Despite the development of integrative databases, building a consensus map of genes, QTL and other loci gathered from multiple maps remains a manual and tedious task. Nevertheless, this is a critical step to reveal co-locations between genes and QTL. Another important matter is to determine whether QTL linked to same traits or related ones is detected in independent experiments and located in the same region, and represents a single locus or not. Statistical tools such as meta-analysis can be used to answer this question. BioMercator has been developed to automate map compilation and QTL meta-analysis, and to visualize co-locations between genes and QTL through a graphical interface. AVAILABILITY: Available upon request (http://moulon/~bioinfo/BioMercator/). Free of charge for academic use.