Selecting high-dimensional mixed graphical models using minimal AIC or BIC forests

Background  

Chow and Liu showed that the maximum likelihood tree for multivariate discrete distributions may be found using a maximum weight spanning tree algorithm, for example Kruskal's algorithm. The efficiency of the algorithm makes it tractable for high-dimensional problems.     

Enlarging a training set for genomic selection by imputation of un-genotyped animals in populations of varying genetic architecture

Background

The most common application of imputation is to infer genotypes of a high-density panel of markers on animals that are genotyped for a low-density panel. However, the increase in accuracy of genomic predictions resulting from an increase in the number of markers tends to reach a plateau beyond a certain density. Another application of imputation is to increase the size of the training set with un-genotyped animals. This strategy can be particularly successful when a set of closely related individuals are genotyped.

Methods

Imputation on completely un-genotyped dams was performed using known genotypes from the sire of each dam, one offspring and the offspring’s sire. Two methods were applied based on either allele or haplotype frequencies to infer genotypes at ambiguous loci. Results of these methods and of two available software packages were compared. Quality of imputation under different population structures was assessed. The impact of using imputed dams to enlarge training sets on the accuracy of genomic predictions was evaluated for different populations, heritabilities and sizes of training sets.

Results

Imputation accuracy ranged from 0.52 to 0.93 depending on the population structure and the method used. The method that used allele frequencies performed better than the method based on haplotype frequencies. Accuracy of imputation was higher for populations with higher levels of linkage disequilibrium and with larger proportions of markers with more extreme allele frequencies. Inclusion of imputed dams in the training set increased the accuracy of genomic predictions. Gains in accuracy ranged from close to zero to 37.14%, depending on the simulated scenario. Generally, the larger the accuracy already obtained with the genotyped training set, the lower the increase in accuracy achieved by adding imputed dams.

Conclusions

Whenever a reference population resembling the family configuration considered here is available, imputation can be used to achieve an extra increase in accuracy of genomic predictions by enlarging the training set with completely un-genotyped dams. This strategy was shown to be particularly useful for populations with lower levels of linkage disequilibrium, for genomic selection on traits with low heritability, and for species or breeds for which the size of the reference population is limited.     

Bacterial colonization of Hydra hatchlings follows a robust temporal pattern

Animals are colonized by complex bacterial communities. The processes controlling community membership and influencing the establishment of the microbial ecosystem during development are poorly understood. Here we aimed to explore the assembly of bacterial communities in Hydra with the broader goal of elucidating the general rules that determine the temporal progression of bacterial colonization of animal epithelia. We profiled the microbial communities in polyps at various time points after hatching in four replicates. The composition and temporal patterns of the bacterial communities were strikingly similar in all replicates. Distinct features included high diversity of community profiles in the first week, a remarkable but transient adult-like profile 2 weeks after hatching, followed by progressive emergence of a stable adult-like pattern characterized by low species diversity and the preponderance of the Betaproteobacterium Curvibacter. Intriguingly, this process displayed important parallels to the assembly of human fecal communities after birth. In addition, a mathematical modeling approach was used to uncover the organizational principles of this colonization process, suggesting that both, local environmental or host-derived factor(s) modulating the colonization rate, as well as frequency-dependent interactions of individual bacterial community members are important aspects in the emergence of a stable bacterial community at the end of development.     

Does small-sided-games’ court area influence metabolic,perceptual, and physical performance parameters of young elite basketball players?

The purpose of this study was to investigate the effect of court size on physiological responses and physical performance of young elite basketball players. Twelve male basketball players (18.6 ± 0.5 years; 88.8 ± 14.5 kg; 192.6 ± 6.5 cm) from an under-19 team performed two small-sided games (matches) with different court areas (28x15 m and 28x9 m; 28x15 and 28x9 protocols). The number of players (3x3) was kept the same in each protocol. The players performed a repeated-sprint ability (RSA) test before and after each match. Blood lactate concentration was collected before (pre) and after (post) the matches, and the session rating of perceived exertion (session-RPE) was determined 30 minutes after the match. Best and mean time in the RSA test were not different between the 28x15 and the 28x9 match protocols (p > 0.05). A significant difference was observed for lactate concentration from pre- to post-match (p < 0.05) in both protocols (28x15 and 28x9); however, there was no significant interaction between protocols. A similar session-RPE mean score (28x15: 7.2 ± 1.4 and 28x9: 6.6 ± 1.4) was detected for both protocols (p > 0.05, ES=0.41). In summary, the results of the current study suggest that the different court areas induced similar responses. Although there was no significant difference in effort perception, players tended to perceive a greater effort in the larger court size.     

A calcium-binding protein with similarity to serum albumin localized to the ER-Golgi network and cell walls of spinach (Spinacia oleracea)

Using polyclonal antibodies raised against human serum albumin (HSA), a 70-kDa microsomal protein with an isoelectric point of approximately 6.5 was detected in spinach ( Spinacia oleracea L.). The protein was purified by selective ammonium sulfate precipitation and anion exchange HPLC. The protein shared 100% identity with the first 15 amino acids at the NH₂ terminus of HSA, including the X-X-H amino acid region, which was identified in HSA as being responsible for binding of copper, zinc, indole derivatives and calcium. Blue staining of the protein with the cationic carbocyanine dye 'Stains-all' and ⁴⁵Ca overlay following SDS-PAGE also suggest that the 70-kDa plant protein binds calcium. The protein reacted positively with carbohydrate specific thymol stain, and the carbohydrates associated with the protein were identified by gas chromatography-mass spectrometry (GC-MS) as galactose and galacturonic acid. The 70-kDa plant protein was present in the detergent-poor phase following Triton X-114 extraction of the microsomal proteins. Cell fractionation using continuous sucrose gradients showed that the protein is present in membrane fractions with high activity of endoplasmic reticulum (ER) and Golgi marker enzymes. Using nitrocellulose tissue prints probed with anti-HSA antibodies, we demonstrated that the protein is present in the apoplastic space of petioles, suggesting that the protein is secreted to the apoplast of cortex cells in plants. Localization and binding properties suggest that the plant protein identified in the present study may participate in secretion processes, possibly involved with the transport of precursors required for cell-wall synthesis.     

Specific biochemical marker-based techniques for the identification of damage to Douglas-fir seed resulting from feeding by the western conifer seed bug, Leptoglossus occidentalis Heidemann (Hemiptera: Coreidae)

Specific biochemical marker-based techniques were tested for their ability to distinguish between seeds of Douglas-fir, Pseudotsuga menziesii (Mirbel) Franco, that were filled or unfilled (aborted) at maturity and those that were damaged or emptied by the western conifer seed bug, Leptoglossus occidentalis Heidemann. A polyclonal antibody raised against salivary gland extracts from L. occidentalis successfully identified residual salivary proteins on Western blots containing proteins from Douglas-fir seeds that had sustained various degrees of seed bug feeding damage. In a single blind experiment, the polyclonal antibody correctly identified 100% of undamaged control, 97% of unfilled control (aborted), and 98% of seed bug damaged seeds. Polyclonal antibodies raised against insoluble alfalfa crystalloid storage protein (11S globulin) detected the depletion of 11S globulin and the subsequent appearance of its hydrolyzed fragments in the soluble protein fraction of Douglas-fir seeds that were fed-upon by the seed bug. Feeding by L. occidentalis nymphs caused ca. 98% depletion of insoluble protein, but only ca. 53% reduction in the amount of soluble protein in seeds that appeared empty on radiographs. By comparison, unfilled (aborted) seeds contained significantly less insoluble and soluble protein than empty seeds that were fed-upon by L. occidentalis; moreover, no crystalloid (11S globulin) breakdown products were generated. The biochemical markers described in this study are reliable tools that can be used to identify conifer seeds that have sustained light to severe damage from L. occidentalis feeding.     

Stringent and reproducible tetracycline-regulated transgene expression by site-specific insertion at chromosomal loci with pre-characterised induction characteristics

Background  

The ability to regulate transgene expression has many applications, mostly concerning the analysis of gene function. Desirable induction characteristics, such as low un-induced expression, high induced expression and limited cellular heterogeneity, can be seriously impaired by chromosomal position effects at the site of transgene integration. Many clones may therefore need to be screened before one with optimal induction characteristics is identified. Furthermore, such screens must be repeated for each new transgene investigated, and comparisons between clones with different transgenes is complicated by their different integration sites.     

An IGF-I promoter polymorphism modifies the relationships between birth weight and risk factors for cardiovascular disease and diabetes at age 36

BACKGROUND: Biochemical testing for pheochromocytoma by measurement of fractionated plasma metanephrines is limited by false positive rates of up to 18% in people without known genetic predisposition to the disease. The plasma normetanephrine fraction is responsible for most false positives and plasma normetanephrine increases with age. The objective of this study was to determine if we could improve the specificity of fractionated plasma measurements, by statistically adjusting for age. METHODS: An age-adjusted metanephrine score was derived using logistic regression from 343 subjects (including 33 people with pheochromocytoma) who underwent fractionated plasma metanephrine measurements as part of investigations for suspected pheochromocytoma at Mayo Clinic Rochester (derivation set). The performance of the age-adjusted score was validated in a dataset of 158 subjects (including patients 23 with pheochromocytoma) that underwent measurements of fractionated plasma metanephrines at Mayo Clinic the following year (validation dataset). None of the participants in the validation dataset had known genetic predisposition to pheochromocytoma. RESULTS: The sensitivity of the age-adjusted metanephrine score was the same as that of traditional interpretation of fractionated plasma metanephrine measurements, yielding a sensitivity of 100% (23/23, 95% confidence interval [CI] 85.7%, 100%). However, the false positive rate with traditional interpretation of fractionated plasma metanephrine measurements was 16.3% (22/135, 95% CI, 11.0%, 23.4%) and that of the age-adjusted score was significantly lower at 3.0% (4/135, 95% CI, 1.2%, 7.4%) (p < 0.001 using McNemar's test). CONCLUSION: An adjustment for age in the interpretation of results of fractionated plasma metanephrines may significantly decrease false positives when using this test to exclude sporadic pheochromocytoma. Such improvements in false positive rate may result in savings of expenditures related to confirmatory imaging.     

Treatment with synthetic brood pheromone (SuperBoost) enhances honey production and improves overwintering survival of package honey bee (Hymenoptera: Apidae) colonies

We evaluated a year-long treatment regime testing synthetic, 10-component, honey bee, Apis mellifera L. (Hymenoptera: Apidae), brood pheromone (SuperBoost; Contech Enterprises Inc., Delta, BC, Canada) on the productivity and vigor of package bee colonies in the lower Fraser Valley of British Columbia, Canada. Fifty-eight newlyestablished 1.3-kg (3-lb) colonies treated three times with SuperBoost at 5-wk intervals starting 30 April 2009 were compared with 52 untreated control colonies. Treated colonies produced 84.3% more honey than untreated control colonies. By 8 September 2009, SuperBoost-treated colonies had 35.4% more adults than untreated colonies. By 28 September, net survival of treated and control colonies was 72.4 and 67.3%, respectively. On 5 October, treated and control colonies were divided into two additional groups, making up four cohorts: SuperBoost-treated colonies treated again during fall and spring build-up feeding with pollen substitute diet (BeePro, Mann Lake Ltd., Hackensack, MN; TIT); controls that remained untreated throughout the year (CCC); colonies treated with SuperBoost in spring-summer 2009 but not treated thereafter (TCC); and original control colonies treated with SuperBoost during the fall and spring build-up feeding periods (CTT). There was no difference among cohorts in consumption of BeePro during fall feeding, but TTT colonies (including daughter colonies split off from parent colonies) consumed 50.8% more diet than CCC colonies during spring build-up feeding. By 21 April, the normalized percentages of the original number of colonies remaining (dead colonies partially offset by splits) were as follows: CCC, 31.4%; CTT, 43.8%; TCC, 53.59%; and TTT, 80.0%. The net benefit of placing 100 newly established package bee colonies on a year-long six-treatment regime with SuperBoost would be US$6,202 (US$62.02 per colony). We conclude that treatment with SuperBoost enhanced the productivity and survival of package bee colonies and hypothesize that similar results could be achieved with established colonies.     

Phylogeographic mitogenomics of Atlantic cod Gadus morhua: Variation in and among trans‐Atlantic,trans‐Laurentian,Northern cod,and landlocked fjord populations

The historical phylogeography, biogeography, and ecology of Atlantic cod (Gadus morhua) have been impacted by cyclic Pleistocene glaciations, where drops in sea temperatures led to sequestering of water in ice sheets, emergence of continental shelves, and changes to ocean currents. High‐resolution, whole‐genome mitogenomic phylogeography can help to elucidate this history. We identified eight major haplogroups among 153 fish from 14 populations by Bayesian, parsimony, and distance methods, including one that extends the species coalescent back to ca. 330 kya. Fish from the Barents and Baltic Seas tend to occur in basal haplogroups versus more recent distribution of fish in the Northwest Atlantic. There was significant differentiation in the majority of trans‐Atlantic comparisons (Φ_ST = .029–.180), but little or none in pairwise comparisons within the Northwest Atlantic of individual populations (Φ_ST = .000–.060) or defined management stocks (Φ_ST = .000–.023). Monte Carlo randomization tests of population phylogeography showed significantly nonrandom trans‐Atlantic phylogeography versus absence of such structure within various partitions of trans‐Laurentian, Northern cod (NAFO 2J3KL) and other management stocks, and Flemish Cap populations. A landlocked meromictic fjord on Baffin Island comprised multiple identical or near‐identical mitogenomes in two major polyphyletic clades, and was significantly differentiated from all other populations (Φ_ST = .153–.340). The phylogeography supports a hypothesis of an eastern origin of genetic diversity ca. 200–250 kya, rapid expansion of a western superhaplogroup comprising four haplogroups ca. 150 kya, and recent postglacial founder populations.