Biomedical subjects

Borys Wróbel

Publications and source records attributed to Borys Wróbel.

6 recordsLinked to original sources

PubMed2006

Topology testing of phylogenies using least squares methods.

BACKGROUND: The least squares (LS) method for constructing confidence sets of trees is closely related to LS tree building methods, in which the goodness of fit of the distances measured on the tree (patristic distances) to the observed distances between taxa is the criterion used for selecting the best topology. The generalized LS (GLS) method for topology testing is often frustrated by the computational difficulties in calculating the covariance matrix and its inverse, which in practice requires approximations. The weighted LS (WLS) allows for a more efficient albeit approximate calculation of the test statistic by ignoring the covariances between the distances. RESULTS: The goal of this paper is to assess the applicability of the LS approach for constructing confidence sets of trees. We show that the approximations inherent to the WLS method did not affect negatively the accuracy and reliability of the test both in the analysis of biological sequences and DNA-DNA hybridization data (for which character-based testing methods cannot be used). On the other hand, we report several problems for the GLS method, at least for the available implementation. For many data sets of biological sequences, the GLS statistic could not be calculated. For some data sets for which it could, the GLS method included all the possible trees in the confidence set despite a strong phylogenetic signal in the data. Finally, contrary to WLS, for simulated sequences GLS showed undercoverage (frequent non-inclusion of the true tree in the confidence set). CONCLUSION: The WLS method provides a computationally efficient approximation to the GLS useful especially in exploratory analyses of confidence sets of trees, when assessing the phylogenetic signal in the data, and when other methods are not available.

Animals↗

PubMed2006

Analysis of the overdispersed clock in the short-term evolution of hepatitis C virus: Using the E1/E2 gene sequences to infer infection dates in a single source outbreak.

The assumption of a molecular clock for dating events from sequence information is often frustrated by the presence of heterogeneity among evolutionary rates due, among other factors, to positively selected sites. In this work, our goal is to explore methods to estimate infection dates from sequence analysis. One such method, based on site stripping for clock detection, was proposed to unravel the clocklike molecular evolution in sequences showing high variability of evolutionary rates and in the presence of positive selection. Other alternatives imply accommodating heterogeneity in evolutionary rates at various levels, without eliminating any information from the data. Here we present the analysis of a data set of hepatitis C virus (HCV) sequences from 24 patients infected by a single individual with known dates of infection. We first used a simple criterion of relative substitution rate for site removal prior to a regression analysis. Time was regressed on maximum likelihood pairwise evolutionary distances between the sequences sampled from the source individual and infected patients. We show that it is indeed the fastest evolving sites that disturb the molecular clock and that these sites correspond to positively selected codons. The high computational efficiency of the regression analysis allowed us to compare the site-stripping scheme with random removal of sites. We demonstrate that removing the fast-evolving sites significantly increases the accuracy of estimation of infection times based on a single substitution rate. However, the time-of-infection estimations improved substantially when a more sophisticated and computationally demanding Bayesian method was used. This method was used with the same data set but keeping all the sequence positions in the analysis. Consequently, despite the distortion introduced by positive selection on evolutionary rates, it is possible to obtain quite accurate estimates of infection dates, a result of especial relevance for molecular epidemiology studies.

Bayes Theorem↗

PubMed2005

Weighted least-squares likelihood ratio test for branch testing in phylogenies reconstructed from distance measures.

A variety of analytical methods is available for branch testing in distance-based phylogenies. However, these methods are rarely used, possibly because the estimation of some of their statistics, especially the covariances, is not always feasible. We show that these difficulties can be overcome if some simplifying assumptions are made, namely distance independence. The weighted least-squares likelihood ratio test (WLS-LRT) we propose is easy to perform, using only the distances and some of their associated variances. If no variances are known, the use of the Felsenstein F-test, also based on weighted least squares, is discussed. Using simulated data and a data set of 43 mammalian mitochondrial sequences we demonstrate that the WLS-LRT performs as well as the generalized least-squares test, and indeed better for a large number of taxa data set. We thus show that the assumption of independence does not negatively affect the reliability or the accuracy of the least-squares approach. The results of the WLS-LRT are no worse than the results of the bootstrap methods, such as the Felsenstein bootstrap selection probability test and the Dopazo test. We also show that WLS-LRT can be applied in instances where other analytical methods are inappropriate. This point is illustrated by analyzing the relationships between human immunodeficiency virus type 1 (HIV-1) sequences isolated from various organs of different individuals.

Animals↗

PubMed2003

The optimal eukaryotic signal for translation initiation from non-AUG codons, present upstream of bacteriophage lambda P cistron, is inactive in Escherichia coli.

Expression of the replication genes of bacteriophage lambda, O and P, is believed to be translationally coupled. However, it was previously noted that, under conditions of amino acid starvation, when O is not synthesized, P continues to be expressed at a relatively high level. The results presented in this report, contrary to the previously presented hypothesis, suggest that an AGACUGGAU sequence (an optimal context for translation initiation from non-AUG codons in eukaryotes, and present upstream the P cistron) is inactive in Escherichia coli. Comparative sequence analysis confirms that such a signal is unlikely to be important for P synthesis. Instead, a weak Shine-Dalgarno sequence may be present upstream the P cistron, and be active in the absence of O gene expression.

Bacteriophage lambda↗

PubMed2002

Evolution of lambdoid replication modules.

Comparison of the putative iteron-binding proteins of lambdoid phages allows us to propose that in the case of lambdoid replication modules, the units on which natural selection acts do not coincide with the open reading frames. Rather, the first replication gene is split into two segments, and its 3' part (corresponding to the C-terminal domain of the iteron-binding protein) forms one unit with the second gene. We also propose from the phylogenetic analysis of phage-encoded homologs of E. coli DnaB and DnaC, that the recombination with the host sequences is not frequent. Accessory ATP-ases for helicase loading (E. coli DnaC homologs) may not be universal replication proteins. Our analysis may suggest that the bacterial helicase loaders might be of phage origin. The comparison of DnaC homologs of enterobacteria and enterobacterial phages supports the experimental data on residues important in interaction with DnaB. We propose that construction of plasmids carrying the replication origins of lambdoid prophages could be useful not only in further research on DNA replication but also on the role of these prophages in shuttling genes for bacterial virulence. The phage replication sequences could be also useful for identification of clinical enterobacterial isolates.

Bacterial Proteins↗

PubMed2000

Vibrio harveyi bioluminescence plays a role in stimulation of DNA repair.

Although the genetics and biochemistry of bacterial luminescence have been investigated extensively, the biological role of this phenomenon remains unclear. Here it is shown that luxA, luxB and luxD mutants (unable to emit light) of the marine bacterium Vibrio harveyi are significantly more sensitive to UV irradiation when cultivated in the dark after irradiation than when cultivated under a white fluorescent lamp. This difference was much less pronounced in the wild-type (luminescent) V. harveyi strain. Survival of UV-irradiated Escherichia coli wild-type cells depended on subsequent cultivation conditions (in the dark or in the presence of external light). However, after UV irradiation, the percentage of surviving E. coli cells that bear V. harveyi genes responsible for luminescence was significantly higher than that of non-luminescent E. coli, irrespective of the subsequent cultivation conditions. Moreover, it is demonstrated that luminescence of V. harveyi can be stimulated by UV irradiation even in diluted cultures, under conditions when light emission by these bacteria is normally impaired due to quorum sensing regulation. It is proposed that luminescent bacteria have an internal source of light which could be used in DNA repair by a photoreactivation process. Therefore, production of internal light ensuring effective DNA repair seems to be at least one of the biological functions of bacterial luminescence.

Bacterial Proteins↗