Higher variability in the number of sexual partners in males can contribute to a higher prevalence of sexually transmitted diseases in females.

By examining published, empirical data we show that men and women consistently differ in the shape of the distribution of the number of sexual partners. The female distribution is always relatively narrow-variance is low-with a big majority of women having a number of partners close to the average. The male distribution is much wider-variance is high-with many men having few sex partners and many others having more partners than most females. Using stochastic modelling we demonstrate that this difference in variance is, in principle, sufficient to cause a difference in the gender prevalence of sexually transmitted diseases: compared to the situation where the genders have identical sex partner distributions, men will reach a lower equilibrium value, while women will stay at the same level (meaning that female prevalence becomes higher than male). We carefully analyse model behaviour and derive approximate expressions for equilibrium prevalences in the two different scenarios. We find that the size of the difference in gender prevalence depends on the variance ratio (the ratio between the variances of the male and female sex partner distributions), on the expected number of life-time partners, and on the probability of disease transmission. We note that in addition to humans, the variance phenomenon described here is likely to play a role for sexually transmitted diseases in other species also. We also show, again by examining published, empirical data, that the female to male prevalence ratio increases with the overall prevalence of a sexually transmitted disease (i.e., the more widespread the disease, the more women are affected). We suggest that this pattern may be caused by the effect described above in highly prevalent sexually transmitted diseases, while its impact in low-prevalence epidemics is surpassed by the action of high-risk individuals (mostly males).

InterMap3D: predicting and visualizing co-evolving protein residues.

SUMMARY: InterMap3D predicts co-evolving protein residues and plots them on the 3D protein structure. Starting with a single protein sequence, InterMap3D automatically finds a set of homologous sequences, generates an alignment and fetches the most similar 3D structure from the Protein Data Bank (PDB). It can also accept a user-generated alignment. Based on the alignment, co-evolving residues are then predicted using three different methods: Row and Column Weighing of Mutual Information, Mutual Information/Entropy and Dependency. Finally, InterMap3D generates high-quality images of the protein with the predicted co-evolving residues highlighted. AVAILABILITY: http://www.cbs.dtu.dk/services/InterMap3D/.

Phylogenetic relationships between Sarcocystis species from reindeer and other Sarcocystidae deduced from ssu rRNA gene sequences.

Six Sarcocystis species from reindeer (S. grueneri, S. rangi, S. tarandivulpes, S. hardangeri, S. rangiferi and S. tarandi) have previously been genetically characterised. The aim of this study was to identify possible definitive hosts for S. hardangeri, S. rangiferi and S. tarandi by including the six species in phylogenetic analyses of the Sarcocystidae, and also to investigate the phylogenetic relationships between the species from reindeer and those from other hosts. The study also aimed at revealing whether the inclusion of six Sarcocystis species from the same intermediate host would have any effect on previously inferred phylogenetic relationships within the Sarcocystidae. The complete small subunit (ssu) rRNA gene sequences of all six Sarcocystis species from reindeer were used in the phylogenetic analyses along with ssu rRNA gene sequences of 85 other members of the Coccidea. Trees were constructed using Bayesian analysis and maximum likelihood estimations. All six Sarcocystis species from reindeer were placed together with other Sarcocystis species using an even-toed ungulate as their intermediate host. The three canine transmitted species, S. grueneri, S. rangi, S. tarandivulpes, formed a sister group to other Sarcocystis species with a canine definitive host. The position of S. hardangeri on the tree suggested that it uses another type of definitive host than the other Sarcocystis species in this clade. Considering the geographical distribution and infection intensity of S. hardangeri, corvid birds are perhaps its most likely definitive hosts. The phylogenetic position, geographical distribution, prevalence and morphological similarity to feline transmitted Sarcocystis species in closely related Cervidae suggest that the most likely definitive hosts of S. rangiferi and S. tarandi are felines, and in Norway notably the lynx. The overall phylogeny of the Sarcocystidae did not change by the inclusion of the six Sarcocystis species from reindeer. This study suggests that phylogentic analysis can be a useful tool in the search for possible definitive hosts for those Sarcocystis species for which they are unknown and difficult to find solely by other methods.

Finding coevolving amino acid residues using row and column weighting of mutual information and multi-dimensional amino acid representation.

BACKGROUND: Some amino acid residues functionally interact with each other. This interaction will result in an evolutionary co-variation between these residues - coevolution. Our goal is to find these coevolving residues. RESULTS: We present six new methods for detecting coevolving residues. Among other things, we suggest measures that are variants of Mutual Information, and measures that use a multidimensional representation of each residue in order to capture the physico-chemical similarities between amino acids. We created a benchmarking system, in silico, able to evaluate these methods through a wide range of realistic conditions. Finally, we use the combination of different methods as a way of improving performance. CONCLUSION: Our best method (Row and Column Weighed Mutual Information) has an estimated accuracy increase of 63% over Mutual Information. Furthermore, we show that the combination of different methods is efficient, and that the methods are quite sensitive to the different conditions tested.

MaxAlign: maximizing usable data in an alignment.

BACKGROUND: The presence of gaps in an alignment of nucleotide or protein sequences is often an inconvenience for bioinformatical studies. In phylogenetic and other analyses, for instance, gapped columns are often discarded entirely from the alignment. RESULTS: MaxAlign is a program that optimizes the alignment prior to such analyses. Specifically, it maximizes the number of nucleotide (or amino acid) symbols that are present in gap-free columns - the alignment area - by selecting the optimal subset of sequences to exclude from the alignment. MaxAlign can be used prior to phylogenetic and bioinformatical analyses as well as in other situations where this form of alignment improvement is useful. In this work we test MaxAlign's performance in these tasks and compare the accuracy of phylogenetic estimates including and excluding gapped columns from the analysis, with and without processing with MaxAlign. In this paper we also introduce a new simple measure of tree similarity, Normalized Symmetric Similarity (NSS) that we consider useful for comparing tree topologies. CONCLUSION: We demonstrate how MaxAlign is helpful in detecting misaligned or defective sequences without requiring manual inspection. We also show that it is not advisable to exclude gapped columns from phylogenetic analyses unless MaxAlign is used first. Finally, we find that the sequences removed by MaxAlign from an alignment tend to be those that would otherwise be associated with low phylogenetic accuracy, and that the presence of gaps in any given sequence does not seem to disturb the phylogenetic estimates of other sequences. The MaxAlign web-server is freely available online at http://www.cbs.dtu.dk/services/MaxAlign where supplementary information can also be found. The program is also freely available as a Perl stand-alone package.

Molecular and epidemiological study on nosocomial transmission of HCV in hemodialysis patients in Brazil.

An epidemiological and molecular study of hepatitis C virus (HCV) infection was carried out in Brazilian hemodialysis centers. A total of 1,095 patients in all 15 hemodialysis centers in the State of Goiás, Brazil, were studied. All patients were interviewed for possible risk factors to HCV infection and serum samples tested for anti-HCV by ELISA and for HCV RNA by nested RT-PCR of the 5' NC region. For sequence analysis, HCV RNA amplification for the NS5B region (nt 8,279-8,619) was performed. The phylogenetic tree was generated with MrBayes, and clusters with support values above 0.85 were considered epidemiologically related. Of the 1,095 patients, 180 were anti-HCV and/or HCV RNA positive, resulting in an overall prevalence of 16.4% (95% CI: 14.3-18.7). The prevalence of HCV infection in the dialysis centers ranged from 0% to 47.7%. Multivariate analysis of risk factors revealed that history of blood transfusion not screened for anti-HCV and length of time on hemodialysis were independently associated with HCV infection in this population. One hundred six samples could be amplified and sequenced in the NS5B region. Among them, plylogenetic tree analysis revealed that 69 sequences form 13 separated clusters, which were supported by credibility intervals ranging from 85% to 100%, indicating a very close relationship among the HCV isolates and therefore a likely transmission of the virus between patients. By combining phylogenetic analysis with epidemiological data, routes of transmission between the clustered-related-patients could be suggested. These findings provide evidence for nosocomial transmission of HCV in Brazilian hemodialysis centers.

Comparative evaluation of word composition distances for the recognition of SCOP relationships.

MOTIVATION: Alignment-free metrics were recently reviewed by the authors, but have not until now been object of a comparative study. This paper compares the classification accuracy of word composition metrics therein reviewed. It also presents a new distance definition between protein sequences, the W-metric, which bridges between alignment metrics, such as scores produced by the Smith-Waterman algorithm, and methods based solely in L-tuple composition, such as Euclidean distance and Information content. RESULTS: The comparative study reported here used the SCOP/ASTRAL protein structure hierarchical database and accessed the discriminant value of alternative sequence dissimilarity measures by calculating areas under the Receiver Operating Characteristic curves. Although alignment methods resulted in very good classification accuracy at family and superfamily levels, alignment-free distances, in particular Standard Euclidean Distance, are as good as alignment algorithms when sequence similarity is smaller, such as for recognition of fold or class relationships. This observation justifies its advantageous use to pre-filter homologous proteins since word statistics techniques are computed much faster than the alignment methods. AVAILABILITY: All MATLAB code used to generate the data is available upon request to the authors. Additional material available at http://bioinformatics.musc.edu/wmetric

EURISWEB--Web-based epidemiological surveillance of antibiotic-resistant pneumococci in day care centers.

BACKGROUND: EURIS (European Resistance Intervention Study) was launched as a multinational study in September of 2000 to identify the multitude of complex risk factors that contribute to the high carriage rate of drug resistant Streptococcus pneumoniae strains in children attending Day Care Centers in several European countries. Access to the very large number of data required the development of a web-based infrastructure - EURISWEB - that includes a relational online database, coupled with a query system for data retrieval, and allows integrative storage of demographic, clinical and molecular biology data generated in EURIS. METHODS: All components of the system were developed using open source programming tools: data storage management was supported by PostgreSQL, and the hypertext preprocessor to generate the web pages was implemented using PHP. The query system is based on a software agent running in the background specifically developed for EURIS. RESULTS: The website currently contains data related to 13,500 nasopharyngeal samples and over one million measures taken from 5,250 individual children, as well as over one thousand pre-made and user-made queries aggregated into several reports, approximately. It is presently in use by participating researchers from three countries (Iceland, Portugal and Sweden). CONCLUSION: An operational model centered on a PHP engine builds the interface between the user and the database automatically, allowing an easy maintenance of the system. The query system is also sufficiently adaptable to allow the integration of several advanced data analysis procedures far more demanding than simple queries, eventually including artificial intelligence predictive models.