Searching PubMed during a Pandemic

Background

The 2009 influenza A(H1N1) pandemic has generated thousands of articles and news items. However, finding relevant scientific articles in such rapidly developing health crises is a major challenge which, in turn, can affect decision-makers'' ability to utilise up-to-date findings and ultimately shape public health interventions. This study set out to show the impact that the inconsistent naming of the pandemic can have on retrieving relevant scientific articles in PubMed/MEDLINE.

Methodology

We first formulated a PubMed search algorithm covering different names of the influenza pandemic and simulated the results that it would have retrieved from weekly searches for relevant new records during the first 10 weeks of the pandemic. To assess the impact of failing to include every term in this search, we then conducted the same searches but omitted in turn “h1n1,” “swine,” “influenza” and “flu” from the search string, and compared the results to those for the full string.

Principal Findings

On average, our core search string identified 44.3 potentially relevant new records at the end of each week. Of these, we determined that an average of 27.8 records were relevant. When we excluded one term from the string, the percentage of records missed out of the total number of relevant records averaged 18.7% for omitting “h1n1,” 13.6% for “swine,” 17.5% for “influenza,” and 20.6% for “flu.”

Conclusions

Due to inconsistent naming, while searching for scientific material about rapidly evolving situations such as the influenza A(H1N1) pandemic, there is a risk that one will miss relevant articles. To address this problem, the international scientific community should agree on nomenclature and the specific name to be used earlier, and the National Library of Medicine in the US could index potentially relevant materials faster and allow publishers to add alert tags to such materials.     

Computational Immunology Meets Bioinformatics: The Use of Prediction Tools for Molecular Binding in the Simulation of the Immune System

We present a new approach to the study of the immune system that combines techniques of systems biology with information provided by data-driven prediction methods. To this end, we have extended an agent-based simulator of the immune response, C-ImmSim, such that it represents pathogens, as well as lymphocytes receptors, by means of their amino acid sequences and makes use of bioinformatics methods for T and B cell epitope prediction. This is a key step for the simulation of the immune response, because it determines immunogenicity. The binding of the epitope, which is the immunogenic part of an invading pathogen, together with activation and cooperation from T helper cells, is required to trigger an immune response in the affected host. To determine a pathogen''s epitopes, we use existing prediction methods. In addition, we propose a novel method, which uses Miyazawa and Jernigan protein–protein potential measurements, for assessing molecular binding in the context of immune complexes. We benchmark the resulting model by simulating a classical immunization experiment that reproduces the development of immune memory. We also investigate the role of major histocompatibility complex (MHC) haplotype heterozygosity and homozygosity with respect to the influenza virus and show that there is an advantage to heterozygosity. Finally, we investigate the emergence of one or more dominating clones of lymphocytes in the situation of chronic exposure to the same immunogenic molecule and show that high affinity clones proliferate more than any other. These results show that the simulator produces dynamics that are stable and consistent with basic immunological knowledge. We believe that the combination of genomic information and simulation of the dynamics of the immune system, in one single tool, can offer new perspectives for a better understanding of the immune system.     

Establishment of a quasi-field trial in <Emphasis Type="Italic">Abies nordmanniana</Emphasis>—test of a new approach to forest tree breeding

This study used DNA markers to establish a quasi-field trial within a production Christmas tree stand produced from seed collected in an open-pollinated clonal seed orchard (CSO). A total of 660 offspring from the CSO, which comprised 99 clones of Abies nordmanniana, were genotyped with 12 microsatellites. Parentage was assigned successfully to 93% and 98% of the progeny at 95% and 80% confidence, respectively. The assignment rate declined only to 90% when the number of markers was reduced to 10. The distribution of parentage to the offspring among the CSO clones was highly skewed. The most successful clone was assigned as parent in 7% of the cases, and only 92 of the 119 potential parental genotypes were assigned as parents. The obtained pedigree was used to estimate breeding values for the CSO clones for five characters relevant for Christmas tree breeding. For high-heritability traits, such as flushing, accurate breeding values could be estimated for a considerable proportion of the clones. To estimate breeding values for low-heritability traits, such as Christmas tree quality score, more genotyped offspring will be required. The largest drawback of the method is the highly skewed distribution of parentage among the parents in the seed orchards, making it difficult to calculate breeding values for all clones. The approach seems well suited for tree breeding that puts more emphasis on pure selection of parental genotypes and less on estimating quantitative genetic parameters.     

Loss of Octarepeats in Two Processed Prion Pseudogenes in the Red Squirrel, Sciurus vulgaris

The N-terminal region of the mammalian prion protein (PrP) contains an 'octapeptide' repeat which is involved in copper binding. This eight- or nine-residue peptide is repeated four to seven times, depending on the species, and polymorphisms in repeat number do occur. Alleles with three repeats are very rare in humans and goats, and deduced PrP sequences with two repeats have only been reported in two lemur species and in the red squirrel, Sciurus vulgaris. We here describe that the red squirrel two-repeat PrP sequence actually represents a retroposed pseudogene, and that an additional and older processed pseudogene with three repeats also occurs in this species as well as in ground squirrels. We argue that repeat numbers may tend to contract rather than expand in prion retropseudogenes, and that functional prion genes with two repeats may not be viable.     

Genomic prediction when some animals are not genotyped

Background

The use of genomic selection in breeding programs may increase the rate of genetic improvement, reduce the generation time, and provide higher accuracy of estimated breeding values (EBVs). A number of different methods have been developed for genomic prediction of breeding values, but many of them assume that all animals have been genotyped. In practice, not all animals are genotyped, and the methods have to be adapted to this situation.

Results

In this paper we provide an extension of a linear mixed model method for genomic prediction to the situation with non-genotyped animals. The model specifies that a breeding value is the sum of a genomic and a polygenic genetic random effect, where genomic genetic random effects are correlated with a genomic relationship matrix constructed from markers and the polygenic genetic random effects are correlated with the usual relationship matrix. The extension of the model to non-genotyped animals is made by using the pedigree to derive an extension of the genomic relationship matrix to non-genotyped animals. As a result, in the extended model the estimated breeding values are obtained by blending the information used to compute traditional EBVs and the information used to compute purely genomic EBVs. Parameters in the model are estimated using average information REML and estimated breeding values are best linear unbiased predictions (BLUPs). The method is illustrated using a simulated data set.

Conclusions

The extension of the method to non-genotyped animals presented in this paper makes it possible to integrate all the genomic, pedigree and phenotype information into a one-step procedure for genomic prediction. Such a one-step procedure results in more accurate estimated breeding values and has the potential to become the standard tool for genomic prediction of breeding values in future practical evaluations in pig and cattle breeding.     

Patterns of woody plant species richness in the Iberian Peninsula: environmental range and spatial scale

Aim Climate‐based models often explain most of the variation in species richness along broad‐scale geographical gradients. We aim to: (1) test predictions of woody plant species richness on a regional spatial extent deduced from macro‐scale models based on water–energy dynamics; (2) test if the length of the climate gradients will determine whether the relationship with woody species richness is monotonic or unimodal; and (3) evaluate the explanatory power of a previously proposed ‘water–energy’ model and regional models at two grain sizes. Location The Iberian Peninsula. Methods We estimated woody plant species richness on grid maps with c. 2500 and 22,500 km² cell size, using geocoded data for the individual species. Generalized additive models were used to explore the relationships between richness and climatic, topographical and substrate variables. Ordinary least squares regression was used to compare regional and more general water–energy models in relation to grain size. Variation partitioning by partial regression was applied to find how much of the variation in richness was related to spatial variables, explanatory variables and the overlap between these two. Results Water–energy dynamics generate important underlying gradients that determine the woody species richness even over a short spatial extent. The relationships between richness and the energy variables were linear to curvilinear, whereas those with precipitation were nonlinear and non‐monotonic. Only a small fraction of the spatially structured variation in woody species richness cannot be accounted for by the fitted variables related to climate, substrate and topography. The regional models accounted for higher variation in species richness than the water–energy models, although the water–energy model including topography performed well at the larger grain size. Elevation range was the most important predictor at all scales, probably because it corrects for ‘climatic error’ due to the unrealistic assumption that mean climate values are evenly distributed in the large grid cells. Minimum monthly potential evapotranspiration was the best climatic predictor at the larger grain size, but actual evapotranspiration was best at the smaller grain size. Energy variables were more important than precipitation individually. Precipitation was not a significant variable at the larger grain size when examined on its own, but was highly significant when an interaction term between itself and substrate was included in the model. Main conclusions The significance of range in elevation is probably because it corresponds to several aspects that may influence species diversity, such as climatic variability within grid cells, enhanced surface area, and location for refugia. The relative explanatory power of energy and water variables was high, and was influenced by the length of the climate gradient, substrate and grain size of the analysis. Energy appeared to have more influence than precipitation, but water availability is also determined by energy, substrate and topographic relief.     

Pseudo-likelihood analysis of codon substitution models with neighbor-dependent rates.

Recently, Markov processes for the evolution of coding DNA with neighbor dependence in the instantaneous substitution rates have been considered. The neighbor dependency makes the models analytically intractable, and previously Markov chain Monte Carlo methods have been used for statistical inference. Using a pseudo-likelihood idea, we introduce in this paper an approximative estimation method which is fast to compute. The pseudo-likelihood estimates are shown to be very accurate, and from analyzing 348 human-mouse coding sequences we conclude that the incorporation of a CpG effect improves the fit of the model considerably.     

Histology of the fusion area between the parasitic male and the female in the deep-sea anglerfish Neoceratias spinifer Pappenheim, 1914 (Teleostei, Ceratioidei)

The article deals primarily with the histology of the fusion area between the head of the male and the skin of the female in two female Neoceratias spinifer, each of which had a single parasitic male attached. In this area, comprising the whole flattened upper part of the male head, the dermis of the male is completely fused with that of the female, leaving no remnants of the epidermis of either. In all other known cases permanent attachment of the parasitic male is accomplished by fusion of separate outgrowths from the male snout and lower jaw and the female skin. In the fusion area of N. spinifer two interconnected blood vascular plexus are present, the one located in the connective tissue of the male head, the other in that of the female skin. It is not known, however, whether the plexus in the female skin is provided with blood from the female blood vascular system, i.e. there is no critical proof of a real continuity between the female blood vascular system and that of the male. The eyes of both parasitic males are very degenerate. There is no histological evidence of degenerative changes in the male digestive system, heart or gills.     

Microhabitat distributions and species interactions of ectoparasites on the gills of cichlid fish in Lake Victoria,Tanzania

Heterogeneous exposure to parasites may contribute to host species differentiation. Hosts often harbour multiple parasite species which may interact and thus modify each other’s effects on host fitness. Antagonistic or synergistic interactions between parasites may be detectable as niche segregation within hosts. Consequently, the within-host distribution of different parasite taxa may constitute an important axis of infection variation among host populations and species. We investigated the microhabitat distributions and species interactions of gill parasites (four genera) infecting 14 sympatric cichlid species in Lake Victoria, Tanzania. We found that the two most abundant ectoparasite genera (the monogenean Cichlidogyrus spp. and the copepod Lamproglena monodi) were non-randomly distributed across the host gills and their spatial distribution differed between host species. This may indicate microhabitat selection by the parasites and cryptic differences in the host–parasite interaction among host species. Relationships among ectoparasite genera were synergistic: the abundances of Cichlidogyrus spp. and the copepods L. monodi and Ergasilus lamellifer tended to be positively correlated. In contrast, relationships among morphospecies of Cichlidogyrus were antagonistic: the abundances of morphospecies were negatively correlated. Together with niche overlap, this suggests competition among morphospecies of Cichlidogyrus. We also assessed the reproductive activity of the copepod species (the proportion of individuals carrying egg clutches), as it may be affected by the presence of other parasites and provide another indicator of the species specificity of the host–parasite relationship. Copepod reproductive activity did not differ between host species and was not associated with the presence or abundance of other parasites, suggesting that these are generalist parasites, thriving in all cichlid species examined from Lake Victoria.