A comparison of univariate and multivariate gene selection techniques for classification of cancer datasets

Background  

Gene selection is an important step when building predictors of disease state based on gene expression data. Gene selection generally improves performance and identifies a relevant subset of genes. Many univariate and multivariate gene selection approaches have been proposed. Frequently the claim is made that genes are co-regulated (due to pathway dependencies) and that multivariate approaches are therefore per definition more desirable than univariate selection approaches. Based on the published performances of all these approaches a fair comparison of the available results can not be made. This mainly stems from two factors. First, the results are often biased, since the validation set is in one way or another involved in training the predictor, resulting in optimistically biased performance estimates. Second, the published results are often based on a small number of relatively simple datasets. Consequently no generally applicable conclusions can be drawn.     

Assessing the potential range expansion of the exotic monk parakeet in Spain

In this study we determine favourable areas for the monk parakeet, Myiopsitta monachus , in peninsular Spain to account for its current distribution and predict its future course according to its potential range. We applied a favourability function based on generalized linear models using the presence/absence of breeding colonies of the species and the values of a set of variables on the 5167 UTM 10 × 10 km squares comprising the study area. We calculated the factor of distribution change in presences predicted by the model, and grouped the variables into explanatory factors performing a variation partitioning to assess the explanatory power of each factor. Our model included six predictors to explain the presence and absence of the species. These predictors were grouped into three factors: human activity, climate, and topography. Purely human influences accounted for 63.8% of the variation of the final model, while topographical variables explained 15.2% and climate only 5.7%. We obtained a high distribution change factor in which the presences of the species were predicted to increase between two- and sevenfold. Taking into account highly favourable squares, we conclude that the species is still absent in more than 72% of potential settlement areas, and thus we expect a continuous increase in the distribution of the species. Human activity is the main force moulding the distribution of the species, and lies behind its fast expansion, which is not only active, but is also passive via releases and escapes. We identified the areas of likely future expansion of the exotic monk parakeet in Spain. The pest status of the species in its native range, together to its distribution trend, should be taken into account by wildlife agencies to consider options for management.     

Determinants for the subcellular localization and function of a nonessential SEDS protein

The Bacillus subtilis SpoVE integral membrane protein is essential for the heat resistance of spores, probably because of its involvement in spore peptidoglycan synthesis. We found that an SpoVE-yellow fluorescent protein (YFP) fusion protein becomes localized to the forespore during the earliest stages of engulfment, and this pattern is maintained throughout sporulation. SpoVE belongs to a well-conserved family of proteins that includes the FtsW and RodA proteins of B. subtilis. These proteins are involved in bacterial shape determination, although their function is not known. FtsW is necessary for the formation of the asymmetric septum in sporulation, and we found that an FtsW-YFP fusion localized to this structure prior to the initiation of engulfment in a nonoverlapping pattern with SpoVE-cyan fluorescent protein. Since FtsW and RodA are essential for normal growth, it has not been possible to identify loss-of-function mutations that would greatly facilitate analysis of their function. We took advantage of the fact that SpoVE is not required for growth to obtain point mutations in SpoVE that block the development of spore heat resistance but that allow normal protein expression and targeting to the forespore. These mutant proteins will be invaluable tools for future experiments aimed at elucidating the function of members of the SEDS (“shape, elongation, division, and sporulation”) family of proteins.     

Infectious salmon anaemia virus (ISAV) isolated from the ISA disease outbreaks in Chile diverged from ISAV isolates from Norway around 1996 and was disseminated around 2005, based on surface glycoprotein gene sequences

Background

All viruses in the family Bunyaviridae possess a tripartite genome, consisting of a small, a medium, and a large RNA segment. Bunyaviruses therefore possess considerable evolutionary potential, attributable to both intramolecular changes and to genome segment reassortment. Hantaviruses (family Bunyaviridae, genus Hantavirus) are known to cause human hemorrhagic fever with renal syndrome or hantavirus pulmonary syndrome. The primary reservoir host of Sin Nombre virus is the deer mouse (Peromyscus maniculatus), which is widely distributed in North America. We investigated the prevalence of intramolecular changes and of genomic reassortment among Sin Nombre viruses detected in deer mice in three western states.

Methods

Portions of the Sin Nombre virus small (S) and medium (M) RNA segments were amplified by RT-PCR from kidney, lung, liver and spleen of seropositive peromyscine rodents, principally deer mice, collected in Colorado, New Mexico and Montana from 1995 to 2007. Both a 142 nucleotide (nt) amplicon of the M segment, encoding a portion of the G2 transmembrane glycoprotein, and a 751 nt amplicon of the S segment, encoding part of the nucleocapsid protein, were cloned and sequenced from 19 deer mice and from one brush mouse (P. boylii), S RNA but not M RNA from one deer mouse, and M RNA but not S RNA from another deer mouse.

Results

Two of 20 viruses were found to be reassortants. Within virus sequences from different rodents, the average rate of synonymous substitutions among all pair-wise comparisons (π_s) was 0.378 in the M segment and 0.312 in the S segment sequences. The replacement substitution rate (π_a) was 7.0 × 10^-4 in the M segment and 17.3 × 10^-4 in the S segment sequences. The low π_a relative to π_s suggests strong purifying selection and this was confirmed by a Fu and Li analysis. The absolute rate of molecular evolution of the M segment was 6.76 × 10^-3 substitutions/site/year. The absolute age of the M segment tree was estimated to be 37 years. In the S segment the rate of molecular evolution was 1.93 × 10^-3 substitutions/site/year and the absolute age of the tree was 106 years. Assuming that mice were infected with a single Sin Nombre virus genotype, phylogenetic analyses revealed that 10% (2/20) of viruses were reassortants, similar to the 14% (6/43) found in a previous report.

Conclusion

Age estimates from both segments suggest that Sin Nombre virus has evolved within the past 37–106 years. The rates of evolutionary changes reported here suggest that Sin Nombre virus M and S segment reassortment occurs frequently in nature.     

Eddy covariance captures four‐phase crassulacean acid metabolism (CAM) gas exchange signature in Agave

Mass and energy fluxes were measured over a field of Agave tequilana in Mexico using eddy covariance (EC) methodology. Data were gathered over 252 d, including the transition from wet to dry periods. Net ecosystem exchanges (F_N,EC) displayed a crassulacean acid metabolism (CAM) rhythm that alternated from CO₂ sink at night to CO₂ source during the day, and partitioned canopy fluxes (F_A,EC) showed a characteristic four‐phase CO₂ exchange pattern. Results were cross‐validated against diel changes in titratable acidity, leaf‐unfurling rates, energy exchange fluxes and reported biomass yields. Projected carbon balance (g C m^?2 year^?1, mean ± 95% confidence interval) indicated the site was a net sink of ?333 ± 24, of which contributions from soil respiration were +692 ± 7, and F_A,EC was ?1025 ± 25. EC estimated biomass yield was 20.1 Mg (dry) ha^?1 year^?1. Average integrated daily F_A,EC was ?234 ± 5 mmol CO₂ m^?2 d^?1 and persisted almost unchanged after 70 d of drought conditions. Regression analyses were performed on the EC data to identify the best environmental predictors of F_A. Results suggest that the carbon acquisition strategy of Agave offers productivity and drought resilience advantages over conventional semi‐arid C3 and C4 bioenergy candidates.     

Identifying key habitats for the conservation of Bonelli's Eagle Aquila fasciata using radiotracking

Identifying the priority habitats of endangered species is crucial to implementing effective conservation actions. We characterize the key habitats used by Bonelli's Eagle Aquila fasciata, an umbrella and flagship species that is endangered in Mediterranean countries. We radiotracked 17 breeding individuals (10 males and seven females) in Catalonia (NE Iberian Peninsula) and used compositional analysis to determine the key habitats in home‐ranges of both sexes. The main habitats identified within the home‐range area were scrubland, coniferous forests, cropland, sclerophyllous forests, rock outcrops and urban areas, with little difference in habitat use between the sexes. Bonelli's Eagles preferred rocky habitats as breeding areas and scrubland as foraging areas, as these hold the highest abundance of their main prey, Rabbits Oryctolagus cuniculus and Red‐legged Partridges Alectoris rufa. Habitat selection varied seasonally in foraging areas: scrubland was the most preferred habitat type during the breeding season, whereas rocky areas were preferred during the non‐breeding season (although scrubland was also highly selected). Urban areas were avoided both as breeding and as foraging areas. Home‐range size was inversely correlated with the proportion of scrubland, suggesting that this is a key habitat for Bonelli's Eagle. To conserve this species effectively, policies that ensure the preservation of the cliffs used as breeding sites, as well as suitable management of the scrubland used for foraging, should be implemented in the areas inhabited by this species. The promotion of traditional land uses and management techniques that will enhance open areas in Mediterranean landscapes should in the future play an essential role in the conservation of Bonelli's Eagle in Mediterranean habitats.     

<Emphasis Type="Italic">Wolbachia</Emphasis> infection increases recapture rate of field-released <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>

Wolbachia pipientis is a commonly occurring endosymbiont with well-characterised effects on host reproductive biology associated with its infection of the gonads. Wolbachia infections are also widespread in somatic tissues and consequently they have the potential to play a much broader role in host biology. Recently, Wolbachia was shown to alter the locomotion of Drosophila melanogaster in response to food cues in the laboratory. To determine whether this laboratory-based phenotype might translate to real differences for insects in the field, we performed a simple mark-release-recapture experiment with Wolbachia-infected D. melanogaster in a forested habitat. We demonstrate that infected flies are recaptured at twice the rate of uninfected flies, although infection does not affect the distance traveled by those flies recaptured. The differences in recapture could be explained by infection-induced changes in physiology or behavior. If generalizable, such changes may affect the interpretation of behavioral studies for Wolbachia-infected insects and have potential implications for the dynamics of Wolbachia infections in natural populations, including situations where Wolbachia-infected insects are being released for biological control.     

Regressing and progressing metastatic lesions: resistance to immunotherapy is predetermined by irreversible HLA class I antigen alterations

Despite the significant efforts to enhance immune reactivity against malignancies the clinical effect of anti-tumor vaccines and cancer immunotherapy is still below expectations. Understanding of the possible causes of such poor clinical outcome has become very important for improvement of the existing cancer treatment modalities. In particular, the critical role of HLA class I antigens in the success of T cell based immunotherapy has led to a growing interest in investigating the expression and function of these molecules in metastatic cancer progression and, especially in response to immunotherapy. In this report, we illustrate that two types of metastatic lesions are commonly generated in response to immunotherapy according to the pattern of HLA class I expression. We found that metastatic lesions, that progress after immunotherapy have low level of HLA class I antigens, while the regressing lesions demonstrate significant upregulation of these molecules. Presumably, immunotherapy changes tumor microenvironment and creates an additional immune selection pressure on tumor cells. As a result, two subtypes of metastatic lesions arise from pre-existing malignant cells: (a) regressors, with upregulated HLA class I expression after therapy, and (b) progressors with resistance to immunotherapy and with low level of HLA class I. Tumor cells with reversible defects (soft lesions) respond to therapy by upregulation of HLA class I expression and regress, while tumor cells with structural irreversible defects (hard lesions) demonstrate resistance to immunostimulation, fail to upregulate HLA class I antigens and eventually progress. These two types of metastases appear independently of type of the immunotherapy used, either non-specific immunomodulators (cytokines or BCG) or autologous tumor vaccination. Similarly, we also detected two types of metastatic colonies in a mouse fibrosarcoma model after in vitro treatment with IFN-gamma. One type of metastases characterized by upregulation of all MHC class I antigens and another type with partial IFN-gamma resistance, namely with lack of expression of L(d)-MHC class I molecule. Our observations may shed new light on the understanding of the mechanisms of tumor escape and might have implications for improvement of the efficacy of cancer immunotherapy.     

Cryptococcal lymphadenitis in a dog.

We describe a case of canine crytococcosis, the clinical symptoms were: feverish syndrome, vomiting and diarrhoeas and bilateral lymphadenitis in superficial lymph nodes. Microbiology and histopathology study of popliteal lymph node biopsy demonstrated the presence of round yeasts of some 3 microm of diameter, which we identified as Cryptococcus neoformans. Thirty months after suspending the medication the dog returned to the surgery; the dog was very thin and it had nervous symptoms; the owners decided it upon euthanasia. After carrying out the necropsy we take samples for their microbiology and histopathology study, both techniques detect to C. neoformans in marrow, CNS tissue and lymph nodes.     

Standard errors of heritabilities for forage breeding nurseries

Estimators for standard errors of heritability for two typical and complex forage breeding models are illustrated with estimates of variance and covariance components from least-squares and restricted maximum likelihood methods. The first experiment (Model 1) is a factorial design (two grazing management factors) with two layers of split plots (populations and grazing periods) and with plants within populations nested beneath the first split. The second model is for a sites pooling of randomized complete block experiments, with plants nested inside plots and with a split in time. One definition of heritability was applied to the plant habit character for both models in a red clover germplasm. Heritability estimates were statistically the same for the two methods for both models.