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Protein structure elucidation from minimal NMR data: the CLOUDS approach.

In this chapter we review automated methods of protein NMR data analysis and expand on the assignment-independent CLOUDS approach. As presented, given a set of reliable NOEs it is feasible to derive a spatial H-atom distribution that provides a low-resolution image of the protein structure. In order to generate such a list of unambiguous NOEs, a probabilistic assessment of the NOE identities (in terms of frequency-labeled H-atom sources) was developed on the basis of Bayesian inference. The methodology, encompassing programs SPI and BACUS, provides a list of "clean" NOEs that does not hinge on prior knowledge of sequence-specific resonance assignments or a preliminary structural model. As such, the combined SPI/BACUS approach, intrinsically adaptable to include 13C- and/or 15N-edited experiments, affords a useful tool for the analysis of NMR data irrespective of whether the adopted structure calculation protocol is assignment-dependent.

Bayes Theorem↗

Estimation of sensitivity and specificity of diagnostic tests and disease prevalence when the true disease state is unknown.

The performance of a new diagnostic test is frequently evaluated by comparison to a perfect reference test (i.e. a gold standard). In many instances, however, a reference test is less than perfect. In this paper, we review methods for estimation of the accuracy of a diagnostic test when an imperfect reference test with known classification errors is available. Furthermore, we focus our presentation on available methods of estimation of test characteristics when the sensitivity and specificity of both tests are unknown. We present some of the available statistical methods for estimation of the accuracy of diagnostic tests when a reference test does not exist (including maximum likelihood estimation and Bayesian inference). We illustrate the application of the described methods using data from an evaluation of a nested polymerase chain reaction and microscopic examination of kidney imprints for detection of Nucleospora salmonis in rainbow trout.

Algorithms↗

Reducing the incidence of epileptic seizures in the Belgian Tervuren through selection.

There is growing evidence that idiopathic epilepsy in the Belgium Tervuren has a genetic foundation. Reducing the incidence of this disorder, which may afflict as much as 17% of the breed, will rely upon the wise selection of parents. Seizure data on 997 dogs from the American Belgian Tervuren Club were collected through questionnaires in which animals were classified into one of four mutually exclusive categories: 1) no seizures observed, 2) one seizure observed, 3) two to five seizures, and 4) more than five seizures. The analysis of this ordered data made use of a threshold model of Bayesian inference. Integration of posterior densities was accomplished through Gibbs sampling. Through this analysis we are able to predict that the offspring of the mating of two non-epileptic dogs has a probability of 0.99 of never suffering from a seizure. The offspring of the mating of two dogs who have each had 1 seizure has a predicted probability 0.58 of never suffering from a seizure. Prevention of this disease is best prescribed through the selection of non-epileptic dogs as parents of future generations.

Animals↗

Mixed graphical models for simultaneous model identification and control applied to the glucose-insulin metabolism.

In this paper a method for model identification of biological systems described by stochastic linear differential equations using a new computational technique for statistical Bayesian inference, namely mixed graphical models in the sense of Lauritzen and Wermuth, is presented. The model is identified in terms of biological model parameters and noise parameters. This non-linear estimation problem is solved by means of an exact inference algorithm. The parameter estimates are given as a-posteriori distributions which can be interpreted as fuzzy possibility distributions. For model-based simulations of the underlying biological system the model parameters are represented as uncertain parameters with the distributions obtained from the estimation procedure. We apply the presented methods to a model for the glucose-insulin metabolism: the Karlsburg model for type I diabetes.

Bayes Theorem↗

Statistical analysis of domino chemical accidents.

A set of chemical accidents is retrieved from the literature and classified with regard to the substance involved and whether domino effects are present. This set of accidents and each of the classes defined are statistically analyzed with respect to its severity and comparison is made between domino and non-domino accidents. The analysis reveals that each accident category shows characteristic patterns in terms of fatalities caused and domino effects likelihood. Moreover, chemical accidents severity frequencies are described by using a two-parameter, revised form of the Pareto probability density function. The range within which the values of the parameters lie is investigated using Bayesian inference.

Accidents, Occupational↗

Phylogeny of the Gyalectales and Ostropales (Ascomycota, Fungi): among and within order relationships based on nuclear ribosomal RNA small and large subunits.

Despite various morphological and anatomical similarities, the two orders Gyalectales (lichenized ascomycetes) and Ostropales (lichenized and non-lichenized ascomycetes) have been considered to be distantly related to each other and their position within the Ascomycota was unsettled. To estimate relationships within these groups and their respective phylogenenetic placement within the Ascomycota, we analyzed DNA sequences from the nuclear small and large subunit ribosomal RNA genes using Maximum Parsimony, Maximum Likelihood, and Bayesian statistics with Markov chain Monte Carlo algorithms. Support for internal branches estimated with bootstrap was compared to Bayesian posterior probabilities. We report here that the Ostropales, in their current circumscription, are paraphyletic, and that the Ostropales s.l. include the Gyalectales and Trapeliaceae. The Unitunicate Ascohymenials are redelineated to include the Ostropales s.l., as defined here, and the Baeomycetaceae. Dimerella and Coenogonium are congeneric, and Petractis thelotremella and P. hypoleuca are reunited with members of the genus Gyalecta. In addition to requiring less computational time, Bayesian inference of phylogeny recovered the same topology as a conventional heuristic search using Maximum Likelihood as the optimization criterion and seems superior to bootstrapping in estimating support for short internal branches.

Ascomycota↗

Snake phylogeny: evidence from nuclear and mitochondrial genes.

We constructed phylogenies of snakes from the c-mos and cytochrome b genes using conventional phylogenetic methods as well as the relatively new method of Bayesian inference. For all methods, there was excellent congruence between the c-mos and cytochrome b genes, implying a high level of support for the shared clades. Our results agree with previous studies in two important respects: first, that the scolecophidians and alethinophidians are monophyletic sister clades; and second, that the Colubroidea is a monophyletic group with the Acrochordidae as its sister clade. However, our results differ from previous studies in the finding that Loxocemus and Xenopeltis cluster with pythons. An additional noteworthy result from our data is that the genera Exiliboa and Ungaliophis, often placed with Tropidophis (and Trachyboa, not included in the present study) in the Tropidophiidae, are in reality boids.

Animals↗

Phylogeny of Passerida (Aves: Passeriformes) based on nuclear and mitochondrial sequence data.

Passerida is a monophyletic group of oscine passerines that includes almost 3500 species (about 36%) of all bird species in the world. The current understanding of higher-level relationships within Passerida is based on DNA-DNA hybridizations [C.G. Sibley, J.E. Ahlquist, Phylogeny and Classification of Birds, 1990, Yale University Press, New Haven, CT]. Our results are based on analyses of 3130 aligned nucleotide sequence data obtained from 48 ingroup and 13 outgroup genera. Three nuclear genes were sequenced: c-myc (498-510 bp), RAG-1 (930 bp), and myoglobin (693-722 bp), as well one mitochondrial gene; cytochrome b (879 bp). The data were analysed by parsimony, maximum-likelihood, and Bayesian inference. The African rockfowl and rockjumper are found to constitute the deepest branch within Passerida, but relationships among the other taxa are poorly resolved--only four major clades receive statistical support. One clade corresponds to Passeroidea of [C.G. Sibley, B.L. Monroe, Distribution and Taxonomy of Birds of the World, 1990, Yale University Press, New Haven, CT] and includes, e.g., flowerpeckers, sunbirds, accentors, weavers, estrilds, wagtails, finches, and sparrows. Starlings, mockingbirds, thrushes, Old World flycatchers, and dippers also group together in a clade corresponding to Muscicapoidea of Sibley and Monroe [op. cit.]. Monophyly of their Sylvioidea could not be corroborated--these taxa falls either into a clade with wrens, gnatcatchers, and nuthatches, or one with, e.g., warblers, bulbuls, babblers, and white-eyes. The tits, penduline tits, and waxwings belong to Passerida but have no close relatives among the taxa studied herein.

Animals↗

Phylogeny and evolution of reproductive modes in Autolytinae (Syllidae, Annelida).

The phylogeny of 31 autolytine taxa (Syllidae, Polychaeta, and Annelida) was estimated based on 16S rDNA and 18S rDNA sequences. Outgroups included 12 non-autolytine syllids and four other annelids from related groups. The phylogeny was used to trace the evolution of the various reproductive strategies (i.e., epigamy, anterior and posterior scissiparity, and gemmiparity) within the group, and it will also serve as a basis for a forthcoming revision of autolytine taxonomy. The two genes were analysed both separately and in combination using parsimony, maximum likelihood, and Bayesian inference. Regardless of method used the combined analysis supported a division of Autolytinae into three major clades: one with epigamous Autolytus; a second comprising Autolytus and Myrianida with posterior scissiparity and gemmiparity; and a third containing Proceraea, Procerastea, and Virchowia with anterior scissiparity. The relationship between these three groups is uncertain. Ancestral reproductive states were reconstructed with parsimony and maximum likelihood, and the results unequivocally support epigamy as the plesiomorphic reproductive mode in Syllidae, and that schizogamy in Syllinae and Autolytinae are separate events. The evolution of reproductive traits is ambiguous within Autolytinae, and either of the different reproductive modes could represent the ancestral state.

Animals↗

Phylogeny reconstruction in the gap between too little and too much divergence: the closest relatives of Senecio jacobaea (Asteraceae) according to DNA sequences and AFLPs.

The species composition and molecular phylogeny of Senecio sect. Jacobaea (Asteraceae; Senecioneae) were studied to identify the closest relatives of Senecio jacobaea. Maximum parsimony and Bayesian inference analyses of DNA sequence data of the plastid (the trnT-L igs, the trnL intron, two parts of the trnK intron, and the psbA-trnH igs) and nuclear genome (ITS1, 5.8S, and ITS2) showed these markers to be suitable to assess the species composition of sect. Jacobaea, identifying 24 species as members of this section. Of these, nine species were not previously assigned to the section. The selected DNA sequence regions, however, showed too little sequence divergence to be optimal for phylogenetic inference within sect. Jacobaea. In contrast, AFLPs proved to be too variable to be used to study relationships between the basal lineages in sect. Jacobaea. Nonetheless, these markers are very useful to study the phylogeny of S. jacobaea and its closest relatives. The combined use of DNA sequence data and AFLPs allowed us to take a major step towards resolving phylogenetic relationships in sect. Jacobaea, identifying Senecio alpinus, Senecio pancicii and Senecio subalpinus (using DNA sequence data) or Senecio chrysanthemoides (using AFLPs) as the closest relatives of S. jacobaea.

Base Sequence↗

Molecular phylogeny of naidid worms (Annelida: Clitellata) based on cytochrome oxidase I.

Naidids are tiny, primarily freshwater oligochaete annelids which reproduce asexually by fission. We investigated the phylogenetic relationships within this group by sequencing 1224 bp of the mitochondrial gene cytochrome oxidase I (COI) from 26 species of naidids (representing 13 of the 23 genera currently recognized), as well as from four tubificids, their closest allies. Although not completely concordant, maximum parsimony and Bayesian inference analyses agreed in several important respects, with no well-supported conflicts. Our study, the first detailed molecular investigation of naidid relationships, suggests that naidids fall into two groups, one comprised of the genus Pristina, and another comprised of all other genera sampled. The clear division of naidids into these two groups best matches an early, simple classification of the group by Lastockin (1924); the more recent classifications proposed by Sperber (1948) and Nemec and Brinkhurst (1987) are not as consistent with our results. We note that our study suggests the genus Stylaria is comprised of two distinct species, Stylaria lacustris and Stylaria fossularis, rather than merely two morphotypes of a single species. Based on our phylogenetic results, we suggest that pigmented eyes evolved only once among naidids but must have been lost multiple times, and that the elongation of the prostomium into a proboscis evolved at least twice independently. The simplest form of fission, architomy (fragmentation), occurs in two of the most basally branching naidid genera, and may represent the plesiomorphic condition for naidids.

Amino Acid Sequence↗

Phylogenetics of the southern African dwarf chameleons, Bradypodion (Squamata: Chamaeleonidae).

The taxonomic relationships within the dwarf chameleons (Bradypodion) of southern Africa have long been controversial. Although informal phenotypic groups have been suggested, the evolutionary relationships among the 15 recognised species in southern Africa have not been previously investigated. To investigate the relationships among species within this genus, fragments of two mitochondrial genes (16S ribosomal RNA and ND2) were sequenced and analysed using maximum parsimony, maximum likelihood and Bayesian inference. All analyses showed congruent topologies, revealing at least 5 well-supported clades distributed across distinct geographic regions. The mtDNA gene tree indicated that in many instances, geographic location has played a role in shaping the evolution of this group, and that the previously suggested phenotypic groupings do not adequately reflect evolutionary relationships. Furthermore, it appears that some of the currently recognised species (described on morphology) are polyphyletic for mitochondrial sequences, most notably those occurring in the isolated forest patches of north-eastern South Africa, near the Drakensberg Escarpment.

Animals↗

The evolutionary history of seahorses (Syngnathidae: Hippocampus): molecular data suggest a West Pacific origin and two invasions of the Atlantic Ocean.

Sequence data derived from four markers (the nuclear RP1 and Aldolase and the mitochondrial 16S rRNA and cytochrome b genes) were used to determine the phylogenetic relationships among 32 species belonging to the genus Hippocampus. There were marked differences in the rate of evolution among these gene fragments, with Aldolase evolving the slowest and the mtDNA cytochrome b gene the fastest. The RP1 gene recovered the highest number of nodes supported by >70% bootstrap values from parsimony analysis and >95% posterior probabilities from Bayesian inference. The combined analysis based on 2317 nucleotides resulted in the most robust phylogeny. A distinct phylogenetic split was identified between the pygmy seahorse, Hippocampus bargibanti, and a clade including all other species. Three species from the western Pacific Ocean included in our study, namely H. bargibanti, H. breviceps, and H. abdominalis occupy basal positions in the phylogeny. This and the high species richness in the region suggests that the genus evolved somewhere in the West Pacific. There is also fairly strong molecular support for the remaining species being subdivided into three main evolutionary lineages: two West Pacific clades and a clade of species present in both the Indo-Pacific and the Atlantic Ocean. The phylogeny obtained herein suggests at least two independent colonization events of the Atlantic Ocean, once before the closure of the Tethyan seaway, and once afterwards.

Animals↗

Setting bounds for the likelihood ratio when multiple hypotheses are postulated.

The interpretation of mixtures of DNA in the forensic context presents particular challenges. The only logical means available for dealing with them is through Bayesian inference, which leads to the formulation, in most cases, of a likelihood ratio which weighs the evidence in favour of two competing hypotheses. However, situations can arise in which additional hypotheses are proposed and the authors discuss one such situation--that where the number of contributors to the mixture is in dispute. A way of dealing with the problem is presented.

Body Fluids↗

A model for case assessment and interpretation.

The authors describe a new approach to decision-making in an operational forensic science organization based on a model, embodying the principles of Bayesian inference, which has been developed through workshops run within the Forensic Science Service for forensic science practitioners. Issues which arise from the idea of pre-assessment of cases are explored by means of a case example.

Bayes Theorem↗

Motion transparency: making models of motion perception transparent.

In daily life our visual system is bombarded with motion information. We see cars driving by, flocks of birds flying in the sky, clouds passing behind trees that are dancing in the wind. Vision science has a good understanding of the first stage of visual motion processing, that is, the mechanism underlying the detection of local motions. Currently, research is focused on the processes that occur beyond the first stage. At this level, local motions have to be integrated to form objects, define the boundaries between them, construct surfaces and so on. An interesting, if complicated case is known as motion transparency: the situation in which two overlapping surfaces move transparently over each other. In that case two motions have to be assigned to the same retinal location. Several researchers have tried to solve this problem from a computational point of view, using physiological and psychophysical results as a guideline. We will discuss two models: one uses the traditional idea known as 'filter selection' and the other a relatively new approach based on Bayesian inference. Predictions from these models are compared with our own visual behaviour and that of the neural substrates that are presumed to underlie these perceptions.

Journal Article↗

Towards a balanced social psychology: causes, consequences, and cures for the problem-seeking approach to social behavior and cognition.

Mainstream social psychology focuses on how people characteristically violate norms of action through social misbehaviors such as conformity with false majority judgments, destructive obedience, and failures to help those in need. Likewise, they are seen to violate norms of reasoning through cognitive errors such as misuse of social information, self-enhancement, and an over-readiness to attribute dispositional characteristics. The causes of this negative research emphasis include the apparent informativeness of norm violation, the status of good behavior and judgment as unconfirmable null hypotheses, and the allure of counter-intuitive findings. The shortcomings of this orientation include frequently erroneous imputations of error, findings of mutually contradictory errors, incoherent interpretations of error, an inability to explain the sources of behavioral or cognitive achievement, and the inhibition of generalized theory. Possible remedies include increased attention to the complete range of behavior and judgmental accomplishment, analytic reforms emphasizing effect sizes and Bayesian inference, and a theoretical paradigm able to account for both the sources of accomplishment and of error. A more balanced social psychology would yield not only a more positive view of human nature, but also an improved understanding of the bases of good behavior and accurate judgment, coherent explanations of occasional lapses, and theoretically grounded suggestions for improvement.

Cognition↗

Molecular study of Dermatocarpon miniatum (Verrucariales) and allied taxa.

The phylogeny of the Dermatocarpon miniatum-complex (Verrucariales, lichenized Ascomycota) was studied using nuclear ITS sequence data by both parsimony and Bayesian inference of phylogeny. The ITS region contains a substantial amount of variation which resolves the relationships of terminal groups, while the more basal clades have low support in the analyses. D. miniatum var. miniatum and var. complicatum are polyphyletic, while var. cirsodes is monophyletic but located within the complex, as are both D. leptophyllum and D. linkolae. The variation within the D. miniatum-complex is significantly greater than that between some transatlantic species such as D. luridum and D. meiophyllizum. The new names D. taminium sp. nov. from the Greater Sonoran area, and D. tenue comb. nov. (syn. D. muehlenbergii var. tenue) are introduced.

Ascomycota↗