Accurate and Robust Genomic Prediction of Celiac Disease Using Statistical Learning

Practical application of genomic-based risk stratification to clinical diagnosis is appealing yet performance varies widely depending on the disease and genomic risk score (GRS) method. Celiac disease (CD), a common immune-mediated illness, is strongly genetically determined and requires specific HLA haplotypes. HLA testing can exclude diagnosis but has low specificity, providing little information suitable for clinical risk stratification. Using six European cohorts, we provide a proof-of-concept that statistical learning approaches which simultaneously model all SNPs can generate robust and highly accurate predictive models of CD based on genome-wide SNP profiles. The high predictive capacity replicated both in cross-validation within each cohort (AUC of 0.87–0.89) and in independent replication across cohorts (AUC of 0.86–0.9), despite differences in ethnicity. The models explained 30–35% of disease variance and up to ∼43% of heritability. The GRS''s utility was assessed in different clinically relevant settings. Comparable to HLA typing, the GRS can be used to identify individuals without CD with ≥99.6% negative predictive value however, unlike HLA typing, fine-scale stratification of individuals into categories of higher-risk for CD can identify those that would benefit from more invasive and costly definitive testing. The GRS is flexible and its performance can be adapted to the clinical situation by adjusting the threshold cut-off. Despite explaining a minority of disease heritability, our findings indicate a genomic risk score provides clinically relevant information to improve upon current diagnostic pathways for CD and support further studies evaluating the clinical utility of this approach in CD and other complex diseases.     

Mycorrhiza, vegetative mobility and responses to disturbance of alpine plants in the northwestern caucasus

The hypothesis of a trade-off between vegetative mobility and mycorrhizal infection has been examined. The rate of root arbuscular-mycorrhizal (AM) infection and the extent of vegetative mobility (clonal with annual mobility more than 2 cm, clonal with annual mobility less than 2 cm, and non-clonal) was determined for 77 species in four alpine grassland communities in the Teberda Nature Reserve, the Northwest Caucasus, Russia. The percentage of AM species was similar (74–77%) in all four communities. The mean rate of AM root infection did not differ significantly between four communities. It was shown that vegetatively mobile species (annual mobility>2 cm) had on average a lower rate of root AM infection than species with low or no vegetative mobility. Our results conform with the mycorrhizal infection-vegetative mobility trade-off hypothesis. Gap-preferring species in a highly disturbed alpine meadow (burrowing activity of small and large mammals) had lower rate of root AM infection than species preferring undisturbed microsites. This pattern was also found within two larger families, viz.Poaceae andAsteraceae.     

Using priority to food access: fattening strategies in dominance-structured willow tit (Parus montanus) flocks

We studied changes in body mass in response to priority to foodaccess by repeatedly weighing free-living willow tits in dominance-structuredflocks. Priority to food access did not correlate to eitheracquisition rate or net turnover of body reserves, but subordinateswith low food availability had larger body reserves than dominants.Removal experiments suggest a causal relationship between rankand the size of reserves. Body reserves of subordinates decreasedwhen their access to food increased after the dominant was removed.Low variability in body mass of subordinates shows that theydo not maintain large reserves in response to uncertain acquisitionof food. Rather, large reserves of low-rank individuals couldserve as insurance for conditions with increasing requirements.Under such conditions, dominants are more likely to claim theirpriority to food, and subordinates would not be able to increasetheir body reserves by feeding.     

Species pool: the concept,its determination and significance for community restoration

Abstract. The concept of species pool is reviewed. It is suggested to maintain the terms regional pool and local pool but replace actual pool by community pool. The regional and local pool are considered as selections from the regional and local flora based on ecological similarity. It is also suggested to include in the community pool a selection of species present only as diaspores in the diaspore bank (including diaspores from the seed rain), the selection being based on the same ecological criteria. Four approaches to determine the species pool are discussed: ecological, functional and phytosociological similarity, and an experimental approach. The phytosociological approach appears to be promising. The species pool is elaborated as a fuzzy set in the sense that each species of a community or a local or regional flora is a member of any community, local or regional species pool with different degrees of membership. This membership is defined as a probability of a species to become part of the community pool of a target community which is a function of the ecological (environmen-tal/functional/phytosociological) similarity of the species with the target community; the shortness of the distance of its nearest populations, the frequency/abundance, the dispersal capacity, the actual presence of dispersal mechanisms, the germinability of newly arrived diaspores, and the longevity of seeds (viability) in the diaspore bank. The information on species pools is needed for designing experiments where the number of species in a community is to be manipulated, for instance in restoration management.     

Use of AMMI and linear regression models to analyze genotype-environment interaction in durum wheat

Summary The joint durum wheat (Triticum turgidum L var durum) breeding program of the International Maize and Wheat Improvement Center (CIMMYT) and the International Center for Agricultural Research in the Dry Areas (ICARDA) for the Mediterranean region employs extensive multilocation testing. Multilocation testing produces significant genotype-environment (GE) interaction that reduces the accuracy for estimating yield and selecting appropriate germ plasm. The sum of squares (SS) of GE interaction was partitioned by linear regression techniques into joint, genotypic, and environmental regressions, and by Additive Main effects and the Multiplicative Interactions (AMMI) model into five significant Interaction Principal Component Axes (IPCA). The AMMI model was more effective in partitioning the interaction SS than the linear regression technique. The SS contained in the AMMI model was 6 times higher than the SS for all three regressions. Postdictive assessment recommended the use of the first five IPCA axes, while predictive assessment AMMI1 (main effects plus IPCA1). After elimination of random variation, AMMI1 estimates for genotypic yields within sites were more precise than unadjusted means. This increased precision was equivalent to increasing the number of replications by a factor of 3.7.     

Intergenotypic interactions among families of loblolly pine (Pinus taeda L.)

Summary The effects of competition on the growth of families of loblolly pine (Pinus taeda, L.) seedlings were investigated. The experimental design made it possible to evaluate the effects of crowding on growth and to determine the types and magnitudes of intergenotypic interactions among pairs of families. The results showed that intergenotypic interactions were both highly variable and pronounced in their effect on early growth. Evidence was also found for precompetition cooperating interactions occurring among seedlings surrounded by neighbors of the same family.     

The seed bank in an estonian calcareous grassland: Comparison of different successional stages

Seed bank species-composition and seed-density were determined in a successional calcareous (alvar) grassland in western Estonia. Three similar study areas were chosen to compare two different successional stages: open alvar grassland and overgrown areas with young pine forest 30 to 40 years old. In both successional stages, the centre and the edge of a relatively uniform stand were examined. Fifteen soil samples (7 cm in diameter, 5 cm deep) were taken from each of twelve sampling sites. The seedling emergence method was used to estimate seeds in the soil samples. A total of 69 species were detected in the seed bank, of which 18 did not occur in the vegetation. Eighty-nine taxa were recorded in the vegetation and of these 38 were not detected in the seed bank. Fifty-one species occurred both in the seed bank and in the vegetation. The three most abundant taxa in the seed bank wereCarex tomentosa, Linum catharticum andPlantago media, which together made up 49% of the seedlings recorded. Differences in the species compositions of seed bank samples from grassland and forest sites were negligible, although the species richness per area of the above-ground vegetation was significantly higher in the open grassland. The only species tending to be lost from forest site vegetation but still occurring in the forest soil seed bank wereArenaria serpylifolia, Cerastium fontanum andLinum catharticum. About half of all the emerged species from all samples belonged to the transient or short-term persistent seed bank. In the grassland sites there were more species which belonged to the transient seed bank than in the forest sites, where the seed bank contained more short-term persistent type seeds. The seed density was significantly higher in forest sites and lower in grassland sites, which may be explained by the better germination conditions in well-illuminated communities. On the basis of the current study it might be assumed that the soil seed banks of overgrown alvar grasslands which include young pine forests can play a certain role in grassland restoration management.     

Eastern gamagrass (Tripsacum dactyloides) root penetration into and chemical properties of claypan soils

Claypans restrict rooting depth and availability of moisture and nutrients to plants during periods of drought. Eastern gamagrass (Tripsacum dactyloides var. dactyloides [L.] L.) often remains green during summer droughts, while other plants turn brown. Questions arose whether eastern gamagrass roots had or could penetrate claypans to obtain needed moisture. Pits were dug (2 m deep) under eastern gamagrass plants that had been growing 50+ and 5+ years at two sites in Missouri. Clay contents were 30 to 50% in soil layers below 30 cm, and moisture was not limiting in these deep soil layers. Soil pH_Ca in the lower soil layers, except at 180 cm, was below 5.0, and in some cases near 4.0. Extractable Al was especially high in the 90 and 120 cm deep soil layers where pH was low. Extractable Ca, Mg, and K increased with soil depth. The eastern gamagrass roots effectively penetrated claypan soils. Root lengths and root weights were extensive to 180 cm depth, and decreased from the surface with soil depth. Roots of eastern gamagrass were aerenchymous (having cellular compartments which allow air movement) at all depths, were mycorrhizal to at least 150 cm depth, and had relatively high tolerance to acidic Al toxic Tatum subsoil (Typic Hapludult) and toxic levels of Al in nutrient solution. The eastern gamagrass roots also provided root channels through claypans, which could enable new eastern gamagrass or other plant roots to grow into deeper soil layers.     

Recovery of forest understories buried by tephra from Mount St. Helens

To determine the effects of tephra (volcanic aerial ejecta) on forest understory plants, six sites were chosen along a tephra depth gradient (23 to 150 mm) northeast of Mount St. Helens, USA. All sites were in old forests beyond the limits of direct blast damage from the volcanic eruption. At each site, 150 one m² plots were permanently marked; all tephra was removed from 50 of these in 1980. Cover and density of plant species were recorded during 1980, 1981, and 1982.Tephra 23 mm deep had almost no effect on cover and density of vascular plants, and reduced bryophyte cover for only two years. Tephra 45 mm deep destroyed almost all bryophytes. Although damaged by 45 mm tephra, deciduous herbs recovered by 1982, but some evergreen species did not. Tephra 75 mm deep reduced herb cover in 1982 to 32% and density to 26% of that in cleared plots. At two sites with an average tephra depth of 150 mm, almost all herbs were eliminated except in microsites where tephra was thin, but shrub abundance was greatly reduced only where snow had been present during tephra deposition. Almost all cover was contributed by plants established previous to the eruption; seedling cover never exceeded 0.2%. Refugia with thin tephra, resulting from erosion, were vital to the survival of many species, especially bryophytes.Nomenclature of vascular plants follows Hitchcock & Cronquist (1973); moss nomenclature follows Lawton (1971).We thank T. Hill, C. Halpern and B. Smith for field assistance. The USDA Forest Service, and especially J. F. Franklin, facilitated entry into the restricted area around Mount St. Helens. This word was supported by the National Science Foundation, USDA Science and Education Administration, and the U.S. Forest Service Pacific Northwest Forest and Range Experiment Station.