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Biomedical subjects

Chris Field

Publications and source records attributed to Chris Field.

6 recordsLinked to original sources

Examining protein structure and similarities by spectral analysis technique.

The spectral envelope, a frequency based technique for analyzing categorical time series, is applied to amino acid sequences to examine their periodicity. The periodic signatures of such sequences is related to the secondary structure of the folding patterns in the gene. For a pair of sequences, we define a spectral envelope covariance which emphasizes the common periodicities in the two sequences. This is used to give a similarity measure for the two sequences which can then be used in a neighbour joining algorithm to construct a phylogeny. We apply the spectral methods to myoglobin sequences from primates and cetaceans. The spectral envelope reflects the structure of this protein and the tree constructed using spectral methods shows strong agreement with published trees. The spectral envelope can be used to explore similarities between and within different protein families. Since we do not require aligned sequences, the spectral methods can be used to create phylogenies across different protein families. We apply the method to 11 protein families from PANDIT obtaining a tree where the families are separated and the relationship among the families is given.

Algorithms↗

Test a clade in phylogenetic trees.

We develop a new method for testing a portion of a tree (called a clade) based on multiple tests of many 4-taxon trees in this paper. This is particularly useful when the phylogenetic tree constructed by other methods have a clade that is difficult to explain from a biological point of view. The statement about the test of the clade can be made through the multiple P values from these individual tests. By controlling the familywise error rate or the false discovery rate (FDR), 4 different tree test methods are evaluated through simulation methods. It shows that the combination of the approximately unbiased (AU) test and the FDR-controlling procedure provides strong power along with reasonable type I error rate and less heavy computation.

Animals↗

The comparison of the confidence regions in phylogeny.

In this paper, several different procedures for constructing confidence regions for the true evolutionary tree are evaluated both in terms of coverage and size without considering model misspecification. The regions are constructed on the basis of tests of hypothesis using six existing tests: Shimodaira Hasegawa (SH), SOWH, star form of SOWH (SSOWH), approximately unbiased (AU), likelihood weight (LW), generalized least squares, plus two new tests proposed in this paper: single distribution nonparametric bootstrap (SDNB) and single distribution parametric bootstrap (SDPB). The procedures are evaluated on simulated trees both with small and large number of taxa. Overall, the SH, SSOWH, AU, and LW tests led to regions with higher coverage than the nominal level at the price of including large numbers of trees. Under the specified model, the SOWH test gives accurate coverage and relatively small regions. The SDNB and SDPB tests led to the small regions with occasional undercoverage. These two procedures have a substantial computational advantage over the SOWH test. Finally, the cutoff levels for the SDNB test are shown to be more variable than those for the SDPB test.

Classification↗

Estimation of rates-across-sites distributions in phylogenetic substitution models.

Previous work has shown that it is often essential to account for the variation in rates at different sites in phylogenetic models in order to avoid phylogenetic artifacts such as long branch attraction. In most current models, the gamma distribution is used for the rates-across-sites distributions and is implemented as an equal-probability discrete gamma. In this article, we introduce discrete distribution estimates with large numbers of equally spaced rate categories allowing us to investigate the appropriateness of the gamma model. With large numbers of rate categories, these discrete estimates are flexible enough to approximate the shape of almost any distribution. Likelihood ratio statistical tests and a nonparametric bootstrap confidence-bound estimation procedure based on the discrete estimates are presented that can be used to test the fit of a parametric family. We applied the methodology to several different protein data sets, and found that although the gamma model often provides a good parametric model for this type of data, rate estimates from an equal-probability discrete gamma model with a small number of categories will tend to underestimate the largest rates. In cases when the gamma model assumption is in doubt, rate estimates coming from the discrete rate distribution estimate with a large number of rate categories provide a robust alternative to gamma estimates. An alternative implementation of the gamma distribution is proposed that, for equal numbers of rate categories, is computationally more efficient during optimization than the standard gamma implementation and can provide more accurate estimates of site rates.

Evolution, Molecular↗

Laryngoscopic intubation: learning and performance.

BACKGROUND: Many healthcare professionals are trained in direct laryngoscopic tracheal intubation (LEI), which is a potentially lifesaving procedure. This study attempts to determine the number of successful LEI exposures required during training to assure competent performance, with special emphasis on defining competence itself. METHODS: Analyses were based on a longitudinal study of novices under training conditions in the operating room. The progress of 438 LEIs performed by the 20 nonanesthesia trainees was monitored by observation and videotape analysis. Eighteen additional LEIs were performed by experienced anesthesiologists to define the standard. A generalized linear, mixed-modelling approach was used to identify key aspects of effective training and performance. The number of tracheal intubations that the trainees were required to perform before acquiring expertise in LEI was estimated. RESULTS: Subjects performed between 18 and 35 laryngoscopic intubations. However, statistical modeling indicates that a 90% probability of a "good intubation" required 47 attempts. Proper insertion and lifting of the laryngoscope were crucial to "good" or "competent" performance of LEI. Traditional features, such as proper head and neck positions, were found to be less important under the study conditions. CONCLUSIONS: This study determined that traditional LEI teaching for nonanesthesia personnel using manikin alone is inadequate. A reevaluation of current standards in LEI teaching for nonanesthesia is required.

Adult↗

Testing for differences in rates-across-sites distributions in phylogenetic subtrees.

It has long been recognized that the rates of molecular evolution vary amongst sites in proteins. The usual model for rate heterogeneity assumes independent rate variation according to a rate distribution. In such models the rate at a site, although random, is assumed fixed throughout the evolutionary tree. Recent work by several groups has suggested that rates at sites often vary across subtrees of the larger tree as well as across sites. This phenomenon is not captured by most phylogenetic models but instead is more similar to the covarion model of Fitch and coworkers. In this article we present methods that can be useful in detecting whether different rates occur in two different subtrees of the larger tree and where these differences occur. Parametric bootstrapping and orthogonal regression methodologies are used to test for rate differences and to make statements about the general differences in the rates at sites. Confidence intervals based on the conditional distributions of rates at sites are then used to detect where the rate differences occur. Such methods will be helpful in studying the phylogenetic, structural, and functional bases of changes in evolutionary rates at sites, a phenomenon that has important consequences for deep phylogenetic inference.

Confidence Intervals↗