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Biomedical subjects

Frank Wright

Publications and source records attributed to Frank Wright.

6 recordsLinked to original sources

Detecting interspecific recombination with a pruned probabilistic divergence measure.

MOTIVATION: A promising sliding-window method for the detection of interspecific recombination in DNA sequence alignments is based on the monitoring of changes in the posterior distribution of tree topologies with a probabilistic divergence measure. However, as the number of taxa in the alignment increases or the sliding-window size decreases, the posterior distribution becomes increasingly diffuse. This diffusion blurs the probabilistic divergence signal and adversely affects the detection accuracy. The present study investigates how this shortcoming can be redeemed with a pruning method based on post-processing clustering, using the Robinson-Foulds distance as a metric in tree topology space. RESULTS: An application of the proposed scheme to three synthetic and two real-world DNA sequence alignments illustrates the amount of improvement that can be obtained with the pruning method. The study also includes a comparison with two established recombination detection methods: Recpars and the DSS (difference of sum of squares) method. AVAILABILITY: Software, data and further supplementary material are available at the following website: http://www.bioss.sari.ac.uk/~dirk/Supplements/

Algorithms↗

Patterns of diversifying selection in the phytotoxin-like scr74 gene family of Phytophthora infestans.

Phytophthora infestans, the organism responsible for the Irish famine, causes late blight, a re-emerging disease of potato and tomato. Little is known about the molecular evolution of P. infestans genes. To identify candidate effector genes (virulence or avirulence genes) that may have co-evolved with the host, we mined expressed sequence tag (EST) data from infection stages of P. infestans for secreted and potentially polymorphic genes. This led to the identification of scr74, a gene that encodes a predicted 74-amino acid secreted cysteine-rich protein with similarity to the Phytophthora cactorum phytotoxin PcF. The expression of scr74 was upregulated approximately 60-fold 2 to 4 days after inoculation of tomato and was also significantly induced during early stages of colonization of potato. The scr74 gene was found to belong to a highly polymorphic gene family within P. infestans with 21 different sequences identified. Using the approximate and maximum likelihood (ML) methods, we found that diversifying selection likely caused the extensive polymorphism observed within the scr74 gene family. Pairwise comparisons of 17 scr74 sequences revealed elevated ratios of nonsynonymous to synonymous nucleotide-substitution rates, particularly in the mature region of the proteins. Using ML, all 21 polymorphic amino acid sites were identified to be under diversifying selection. Of these 21 amino acids, 19 are located in the mature protein region, suggesting that selection may have acted on the functional portions of the proteins. Further investigation of gene copy number and organization revealed that the scr74 gene family comprises at least three copies located in a region of no more than 300 kb of the P. infestans genome. We found evidence that recombination contributed to sequence divergence within at least one gene locus. These results led us to propose an evolutionary model that involves gene duplication and recombination, followed by functional divergence of scr74 genes. This study provides support for using diversifying selection as a criterion for identifying candidate effector genes from sequence databases.

Algal Proteins↗

TOPALi: software for automatic identification of recombinant sequences within DNA multiple alignments.

SUMMARY: TOPALi is a new Java graphical analysis application that allows the user to identify recombinant sequences within a DNA multiple alignment (either automatically or via manual investigation). TOPALi allows a choice of three statistical methods to predict the positions of breakpoints due to past recombination. The breakpoint predictions are then used to identify putative recombinant sequences and their relationships to other sequences. In addition to its sophisticated interface, TOPALi can import many sequence formats, estimate and display phylogenetic trees and allow interactive analysis and/or automatic HTML report generation. AVAILABILITY: TOPALi is freely available from http://www.bioss.ac.uk/software.html

Computer Graphics↗

A Bayesian approach to discriminate between alternative DNA sequence segmentations.

MOTIVATION: As a result of recombination or rate variation, a DNA sequence alignment may have a mosaic structure, where different segments correspond to different evolutionary histories. While several methods have been developed to predict DNA mosaic structures, they do not properly address the question of whether the predicted segmentation itself is statistically significant, or whether it is significantly better than an alternative mosaic structure predicted with another method. The objective of the present article is to devise an approximate Bayesian hypothesis test to discriminate between alternative candidate mosaic structures. RESULTS: We have applied the proposed discrimination scheme to various synthetic and real-world DNA sequence alignments. On the synthetic data, the algorithm identified the true mosaic structure in nine out of ten cases. On the real-world sequence alignments, it selected the same mosaic structures as predicted in the literature.

Algorithms↗

Molecular characterization of pigmented and nonpigmented isolates of Mycobacterium avium subsp. paratuberculosis.

Five pigmented isolates of Mycobacterium avium subsp. paratuberculosis were examined by pulsed-field gel electrophoresis (PFGE), IS900 restriction fragment length polymorphism (IS900-RFLP), and IS1311 polymorphism analysis using PCR. All of the pigmented isolates exhibited one of three distinct PFGE profiles with SnaBI, designated 9, 10, and 11, and with SpeI, designated 7, 8, and 9, which generated three multiplex profiles designated [9-7], [10-8], and [11-9]. All of the pigmented isolates had the same IS900-RFLP BstEII and PvuII profiles. The IS900-RFLP BstEII profile was new, but the IS900-RFLP PvuII profile corresponded to PvuII type 6 of a sheep strain described by Cousins and colleagues (D. V. Cousins, S. N. Williams, A. Hope, and G. J. Eamens, Aust. Vet. J. 78:184-190, 2000). IS1311-PCR analysis typed all of the pigmented isolates as sheep (S) strains. The genetic relationship between pigmented and nonpigmented isolates was investigated by using multiplex PFGE data from the analysis of both the 5 pigmented isolates and 88 nonpigmented isolates of M. avium subsp. paratuberculosis from a variety of host species and geographic locations. It was possible to classify the isolates into two distinct types designated type I, comprising the pigmented isolates, and type II, comprising the nonpigmented isolates, which exhibit a very broad host range.

Animals↗

Correlates of medication knowledge and adherence: findings from the residency research network of South Texas.

BACKGROUND: Medication adherence is a complex phenomenon, influenced by a variety of factors. Most adherence research focuses on one medicine and does not represent the realities of clinical family medicine. This analysis examined factors associated with medication knowledge and adherence in family medicine patients with chronic conditions. METHODS: The Residency Research Network of South Texas (RRNeST) enrolled 150 patients with chronic disease who "sometimes have trouble taking medicines." Seventy-five percent were Latinos. This cross-sectional analysis used baseline survey data from an intervention study. Investigators correlated medication knowledge and adherence with known predictors--patient, health, medication, economic, and physician factors. New variables related to patients' motivation to change treatment behaviors ("importance" and "confidence") were also included. RESULTS: Linear regression analysis demonstrated that patient satisfaction, education level, and confidence were associated with better medication knowledge. Higher confidence, Spanish language, better functional and health status, and more prescription medicines were correlated with medication adherence. CONCLUSIONS: We recommend that family physicians enhance medication adherence by providing good information about treatment and counseling strategies to build patients' confidence. Our findings suggest that poor health status can be a barrier to, rather than a motivator for, treatment adherence.

Adult↗