Discerning mechanistically rewired biological pathways by cumulative interaction heterogeneity statistics.

Changes in response of a biological pathway could be a consequence of either pathway rewiring, changed input, or a combination of both. Most pathway analysis methods are not designed for mechanistic rewiring such as regulatory element variations. This limits our understanding of biological pathway evolution. Here we present a Q-method to discern whether changed pathway response is caused by mechanistic rewiring of pathways due to evolution. The main innovation is a cumulative pathway interaction heterogeneity statistic accounting for rewiring-specific effects on the rate of change of each molecular variable across conditions. The Q-method remarkably outperformed differential-correlation based approaches on data from diverse biological processes. Strikingly, it also worked well in differentiating rewired chaotic systems, whose dynamics are notoriously difficult to predict. Applying the Q-method on transcriptome data of four yeasts, we show that pathway interaction heterogeneity for known metabolic and signaling pathways is indeed a predictor of interspecies genetic rewiring due to unbalanced TATA box-containing genes among the yeasts. The demonstrated effectiveness of the Q-method paves the way to understanding network evolution at the resolution of functional biological pathways.

Cotton QTLdb: a cotton QTL database for QTL analysis, visualization, and comparison between Gossypium hirsutum and G. hirsutum × G. barbadense populations.

KEY MESSAGE: A specialized database currently containing more than 2200 QTL is established, which allows graphic presentation, visualization and submission of QTL. In cotton quantitative trait loci (QTL), studies are focused on intraspecific Gossypium hirsutum and interspecific G. hirsutum × G. barbadense populations. These two populations are commercially important for the textile industry and are evaluated for fiber quality, yield, seed quality, resistance, physiological, and morphological trait QTL. With meta-analysis data based on the vast amount of QTL studies in cotton it will be beneficial to organize the data into a functional database for the cotton community. Here we provide a tool for cotton researchers to visualize previously identified QTL and submit their own QTL to the Cotton QTLdb database. The database provides the user with the option of selecting various QTL trait types from either the G. hirsutum or G. hirsutum × G. barbadense populations. Based on the user's QTL trait selection, graphical representations of chromosomes of the population selected are displayed in publication ready images. The database also provides users with trait information on QTL, LOD scores, and explained phenotypic variances for all QTL selected. The CottonQTLdb database provides cotton geneticist and breeders with statistical data on cotton QTL previously identified and provides a visualization tool to view QTL positions on chromosomes. Currently the database (Release 1) contains 2274 QTLs, and succeeding QTL studies will be updated regularly by the curators and members of the cotton community that contribute their data to keep the database current. The database is accessible from http://www.cottonqtldb.org.

A comparative meta-analysis of QTL between intraspecific Gossypium hirsutum and interspecific G. hirsutum × G. barbadense populations.

KEY MESSAGE: Based on 1075 and 1059 QTL from intraspecific Upland and interspecific Upland × Pima populations, respectively, the identification of QTL clusters and hotspots provides a useful resource for cotton breeding. Mapping of quantitative trait loci (QTL) is a pre-requisite of marker-assisted selection for crop yield and quality. Recent meta-analysis of QTL in tetraploid cotton (Gossypium spp.) has identified regions of the genome with high concentrations of QTL for various traits called clusters and specific trait QTL called hotspots or meta-QTL (mQTL). However, the meta-analysis included all population types of Gossypium mixing both intraspecific G. hirsutum and interspecific G. hirsutum × G. barbadense populations. This study used 1,075 QTL from 58 publications on intraspecific G. hirsutum and 1,059 QTL from 30 publications on G. hirsutum × G. barbadense populations to perform a comprehensive comparative analysis of QTL clusters and hotspots between the two populations for yield, fiber and seed quality, and biotic and abiotic stress tolerance. QTL hotspots were further analyzed for mQTL within the hotspots using Biomercator V3 software. The ratio of QTL between the two population types was proportional yet differences in hotspot type and placement were observed between the two population types. However, on some chromosomes QTL clusters and hotspots were similar between the two populations. This shows that there are some universal QTL regions in the cultivated tetraploid cotton which remain consistent and some regions which differ between population types. This study for the first time elucidates the similarities and differences in QTL clusters and hotspots between intraspecific and interspecific populations, providing an important resource to cotton breeding programs in marker-assisted selection .

A comprehensive meta QTL analysis for fiber quality, yield, yield related and morphological traits, drought tolerance, and disease resistance in tetraploid cotton.

BACKGROUND: The study of quantitative trait loci (QTL) in cotton (Gossypium spp.) is focused on traits of agricultural significance. Previous studies have identified a plethora of QTL attributed to fiber quality, disease and pest resistance, branch number, seed quality and yield and yield related traits, drought tolerance, and morphological traits. However, results among these studies differed due to the use of different genetic populations, markers and marker densities, and testing environments. Since two previous meta-QTL analyses were performed on fiber traits, a number of papers on QTL mapping of fiber quality, yield traits, morphological traits, and disease resistance have been published. To obtain a better insight into the genome-wide distribution of QTL and to identify consistent QTL for marker assisted breeding in cotton, an updated comparative QTL analysis is needed. RESULTS: In this study, a total of 1,223 QTL from 42 different QTL studies in Gossypium were surveyed and mapped using Biomercator V3 based on the Gossypium consensus map from the Cotton Marker Database. A meta-analysis was first performed using manual inference and confirmed by Biomercator V3 to identify possible QTL clusters and hotspots. QTL clusters are composed of QTL of various traits which are concentrated in a specific region on a chromosome, whereas hotspots are composed of only one trait type. QTL were not evenly distributed along the cotton genome and were concentrated in specific regions on each chromosome. QTL hotspots for fiber quality traits were found in the same regions as the clusters, indicating that clusters may also form hotspots. CONCLUSIONS: Putative QTL clusters were identified via meta-analysis and will be useful for breeding programs and future studies involving Gossypium QTL. The presence of QTL clusters and hotspots indicates consensus regions across cultivated tetraploid Gossypium species, environments, and populations which contain large numbers of QTL, and in some cases multiple QTL associated with the same trait termed a hotspot. This study combines two previous meta-analysis studies and adds all other currently available QTL studies, making it the most comprehensive meta-analysis study in cotton to date.