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PubMed2005

Molecular evolution and phylogeny of sipunculan hemerythrins.

We sequenced seven new hemerythrin (Hr) and myohemerythrin (myoHr) cDNAs from Sipunculus nudus and Golfingia vulgaris vulgaris, thus providing new comparative data that significantly increase the set of the known Hr and myoHr sequences. Bayesian inference, maximum likelihood, and maximum parsimony phylogenetic analyses were performed to investigate the evolutionary relationships among the sipunculan and annelid Hr and myoHr sequences. Annelid myoHrs and sipunculan Hrs were resolved as monophyletic groups. Conversely sipunculan myoHrs did not form a clade. The Hrs having an octameric quaternary structure were resolved as a monophyletic group. The octameric cluster includes the Hr sequences of G. v. vulgaris, Themiste zostericola, Themiste discriptum, and Phascolopsis gouldii. Siphonosoma cumanense Hr, which has a trimeric quaternary structure, assumes a sister group position of the octameric clade. The S. nudus Hrs, having a quaternary structure that is not well resolved, assume an isolate position within the Hrs clade. Likelihood-based analyses reveal that purifying selection mainly characterized the evolution of Hr and myoHr. We suggest that starting from a common gene ancestor, two distinct quaternary structures evolved in the sipunculan Hrs and this differentiation was probably favored by the acquisition of distinct physiological advantages.

Amino Acid Sequence↗
PubMed2006

Evaluating Neanderthal genetics and phylogeny.

The retrieval of Neanderthal (Homo neanderthalsensis) mitochondrial DNA is thought to be among the most significant ancient DNA contributions to date, allowing conflicting hypotheses on modern human (Homo sapiens) evolution to be tested directly. Recently, however, both the authenticity of the Neanderthal sequences and their phylogenetic position outside contemporary human diversity have been questioned. Using Bayesian inference and the largest dataset to date, we find strong support for a monophyletic Neanderthal clade outside the diversity of contemporary humans, in agreement with the expectations of the Out-of-Africa replacement model of modern human origin. From average pairwise sequence differences, we obtain support for claims that the first published Neanderthal sequence may include errors due to postmortem damage in the template molecules for PCR. In contrast, we find that recent results implying that the Neanderthal sequences are products of PCR artifacts are not well supported, suffering from inadequate experimental design and a presumably high percentage (>68%) of chimeric sequences due to "jumping PCR" events.

Animals↗
PubMed2006

Psychometric function for nectar volume perception of a flower-visiting bat.

For foraging pollinators one aspect of floral quality is the volume of nectar available. Thus, nectar-feeding animals should be able to estimate volumes of received nectar. In this study, we determined the psychometric function for nectar volume discrimination of a Neotropical flower-visiting bat Glossophaga soricina. For this, we examined the ability of bats to discriminate between two nectar volumes in a two-alternative forced-choice paradigm. We used a Bayesian inference approach to determine psychometric functions. From the derived psychometric function we assessed the discrimination threshold at a value of 0.69. G. soricina could clearly distinguish between two volumes, when the difference between the two nectar volumes divided by their average exceeded this value. This indicates that bats possess a sense for the perception and discrimination of volumes of nectar that is better developed than in honeybees.

Animals↗
PubMed2003

Estimation of single-trial multicomponent ERPs: differentially variable component analysis (dVCA).

A Bayesian inference framework for estimating the parameters of single-trial, multicomponent, event-related potentials is presented. Single-trial recordings are modeled as the linear combination of ongoing activity and multicomponent waveforms that are relatively phase-locked to certain sensory or motor events. Each component is assumed to have a trial-invariant waveform with trial-dependent amplitude scaling factors and latency shifts. A Maximum a Posteriori solution of this model is implemented via an iterative algorithm from which the component's waveform, single-trial amplitude scaling factors and latency shifts are estimated. Multiple components can be derived from a single-channel recording based on their differential variability, an aspect in contrast with other component analysis techniques (e.g., independent component analysis) where the number of components estimated is equal to or smaller than the number of recording channels. Furthermore, we show that, by subtracting out the estimated single-trial components from each of the single-trial recordings, one can estimate the ongoing activity, thus providing additional information concerning task-related brain dynamics. We test this approach, which we name differentially variable component analysis (dVCA), on simulated data and apply it to an experimental dataset consisting of intracortically recorded local field potentials from monkeys performing a visuomotor pattern discrimination task.

Algorithms↗
PubMed2005

The ITS2 ribosomal DNA of Anopheles beklemishevi and further remarks on the phylogenetic relationships within the Anopheles maculipennis group of species (Diptera: Culicidae).

Anopheles beklemishevi specimens from Russia were analysed by their ITS2 ribosomal DNA sequence to amend and to specify the phylogenetic tree of the Anopheles maculipennis species complex. Surprisingly, with 638 base pairs, the ITS2 regions of all the 34 An beklemishevi specimens examined were considerably longer than those of all their sibling species. Sequence alignment with GenBank derived sequences of the other siblings was only possible in the beginning (for approx. 335 bp) and at the end (for approx. 150 bp) of the PCR-amplified DNA fragment, whereas in the middle, the An beklemishevi DNA sequence found no counterpart in sequences of the other siblings. Closer analysis of this intermediate part suggests a duplicated insertion of about 140 bp that has undergone subsequent mutational changes. Due to this large putative insertion, computerized phylogenetic analysis by the Bayesian inference method locates An beklemishevi in a closer relationship to the nearctic than to the palaearctic sibling species. However, when only ITS2 regions are compared, that have corresponding sequences in the other siblings, An beklemishevi forms a lineage with the palaearctic species although it is still most remotely related. It is hypothesized that during the evolution An beklemishevi separated first from the common ancestor of the palaearctic species, which had presumably made its way from the Nearctic to the Palaearctic.

Animals↗
PubMed2004

Genome sequences of Agropyron mosaic virus and Hordeum mosaic virus support reciprocal monophyly of the genera Potyvirus and Rymovirus in the family Potyviridae.

Assignment of mite-transmitted species to the genus Rymovirus (family Potyviridae) has changed several times, and the status of the genus has been questioned. To address this issue, complete genome sequences of the rymoviruses Agropyron mosaic virus (AgMV) and Hordeum mosaic virus (HoMV) were determined. AgMV (9540 nucleotides) and HoMV (9463 nucleotides) each encode a single polyprotein with proteinase cleavage sites demarcating protein products characteristic of monopartite species of the family Potyviridae. Of the described species of Potyviridae, AgMV and HoMV are most closely related to each other (68.5% nucleotide and 71.6% amino acid sequence identity) and equidistant (about 53% nucleotide and about 49% amino acid sequence identity) from a third rymovirus, Ryegrass mosaic virus (RGMV). Phylogenetic analyses by neighbor joining, maximum parsimony, and Bayesian inference each grouped the three Rymovirus species in an exclusive clade distinct from a clade containing 34 species of the genus Potyvirus. Because AgMV, HoMV, and RGMV share a reciprocal monophyletic relationship with species of the genus Potyvirus and are divergent in sequence and type of vector, the genus Rymovirus should be retained as a taxonomic unit within the family Potyviridae.

Agropyron↗
PubMed2006

Sampling and decision rules used by honey bees in a foraging arena.

Animals must continuously choose among various available options to exploit the most profitable resource. They also need to keep themselves updated about the values of all available options, since their relative values can change quickly due to depletion or exploitation by competitors. While the sampling and decision rules by which foragers profitably exploit a flower patch have attracted a great deal of attention in theory and experiments with bumble bees, similar rules for honey bee foragers, which face similar foraging challenges, are not as well studied. By presenting foragers of the honey bee Apis cerana with choice tests in a foraging arena and recording their behavior, we investigate possible sampling and decision rules that the foragers use to choose one option over another and to track other options. We show that a large part of the sampling and decision-making process of a foraging honey bee can be explained by decomposing the choice behavior into dichotomous decision points and incorporating the cost of sampling. The results suggest that a honey bee forager, by using a few simple rules as part of a Bayesian inference process, is able to effectively deal with the complex task of successfully exploiting foraging patches that consist of dynamic and multiple options.

Animals↗
PubMed2005

Bayes' theorem: a negative example of a RCT on grommets in children with glue ear.

Bayesian inference presupposes that practitioners' belief in the effectiveness of medical intervention is the product of prior belief and recent evidence from studies. Although increasingly used, up to now the posterior belief calculated according to the theorem has not been compared with an empirically measured posterior belief. We conducted a RCT, which was preceded by elicitation of prior beliefs among ENT-surgeons, and which was followed by elicitation of posterior beliefs among ENT-surgeons, 1 year after completion of the trial. We compared the posterior beliefs of ENT-surgeons about the effect of grommets in children with glue ears, as predicted by Bayes' theorem with actual measured posterior beliefs. The distribution of the measured posterior beliefs was not in line with the calculated posterior, but almost identical to the distribution of the measured prior beliefs. The results showed that our trial had little or no impact on the beliefs of the ENT-surgeons, i.e. they did not adjust their belief to the extent that was expected according to Bayes' theorem.

Bayes Theorem↗
PubMed2005

Modelling the progression towards duodenal cancer among patients with familial polyposis on the basis of two different score profiles.

The objective was to design a method that considers, on clinical arguments, the likely existence of patient subgroups with different evolution profiles. The method is applied in familial adenomatous polyposis to predict the proportion of patients that would develop duodenal cancer. A subject-specific linear mixed-effects model was elaborated to explicitly model heterogeneity in regression parameters. The estimates of the parameters were obtained by Bayesian inference using Gibbs sampling. The application concerned two potential polyposis subgroups: stable-state and progressive. Each patient's score was expressed in function of his putative subgroup, the reference subgroup mean score (intercept), the rate of change (slope), and time. The estimated proportion of stable-state patients was 35%. In progressive-state patients, the estimated annual score increase was 0.38 (95% CI: 0.27-0.48). The regression model predicted that the proportion of patients with a score > or = 9 is near 43% at age 60 (36-50%) and 50% at 70 (43-57%). The method indicates the evolution profile of each subject, which facilitates therapeutic decisions. The modelling may be extended to other more complex situations with several subgroups, with different change rates, or with various genetic or therapeutic profiles.

Adenomatous Polyposis Coli↗
PubMed2006

An alternative competing risk model to the Weibull distribution for modelling aging in lifetime data analysis.

A simple competing risk distribution as a possible alternative to the Weibull distribution in lifetime analysis is proposed. This distribution corresponds to the minimum between exponential and Weibull distributions. Our motivation is to take account of both accidental and aging failures in lifetime data analysis. First, the main characteristics of this distribution are presented. Then, the estimation of its parameters are considered through maximum likelihood and Bayesian inference. In particular, the existence of a unique consistent root of the likelihood equations is proved. Decision tests to choose between an exponential, Weibull and this competing risk distribution are presented. And this alternative model is compared to the Weibull model from numerical experiments on both real and simulated data sets, especially in an industrial context.

Aging↗
PubMed2006

Bayesian modelling of an epidemic of severe acute respiratory syndrome.

This paper analyses data arising from a SARS epidemic in Shanxi province of China involving a total of 354 people infected with SARS-CoV between late February and late May 2003. Using Bayesian inference, we have estimated critical epidemiological determinants. The estimated mean incubation period was 5.3 days (95% CI 4.2-6.8 days), mean time to hospitalisation was 3.5 days (95% CI 2.8-3.6 days), mean time from symptom onset to recovery was 26 days (95% CI 25-27 days) and mean time from symptom onset to death was 21 days (95% CI 16-26 days). The reproduction ratio was estimated to be 4.8 (95% CI 2.2-8.8) in the early part of the epidemic (February and March 2003) reducing to 0.75 (95% CI 0.65-0.85) in the later part of the epidemic (April and May 2003). The infectivity of symptomatic SARS cases in hospital and in the community was estimated. Community SARS cases caused transmission to others at an estimated rate of 0.4 per infective per day during the early part of the epidemic, reducing to 0.2 in the later part of the epidemic. For hospitalised patients, the daily infectivity was approximately 0.15 early in the epidemic, but fell to 0.0006 in the later part of the epidemic. Despite the lower daily infectivity level for hospitalised patients, the long duration of the hospitalisation led to a greater number of transmissions within hospitals compared with the community in the early part of the epidemic, as estimated by this study. This study investigated the individual infectivity profile during the symptomatic period, with an estimated peak infectivity on the ninth symptomatic day.

Bayes Theorem↗
PubMedDate not supplied

Medical expert systems based on causal probabilistic networks.

Causal probabilistic networks (CPNs) offer new methods by which you can build medical expert systems that can handle all types of medical reasoning within a uniform conceptual framework. Based on the experience from a commercially available system and a couple of large prototype systems, it appears that CPNs are now an attractive alternative to other methods. A CPN is an intensional model of a domain, and it is therefore conceptually much closer to qualitative reasoning systems and to simulation systems than to rule-based or logic-based systems. Recent progress in Bayesian inference in networks has yielded computationally efficient methods. The inference method used follows the fundamental axioms of probability theory, and gives a sound framework for causal and diagnostic (deductive and abductive) reasoning under uncertainty. Experience with the prototypes indicates that it may be possible to use decision theory as a rational approach to test planning and therapy planning. The way in which knowledge is acquired and represented in CPNs makes it easy to express 'deep knowledge' for example in the form of physiological models, and the facilities for learning make it possible to make a smooth transition from expert opinion to statistics based on empirical data.

Artificial Intelligence↗
PubMed1996

Non-medical influences on medical decision-making.

BACKGROUND: The influence of non-medical factors on physicians' decision-making has been documented in many observational studies, but rarely in an experimental setting capable of demonstrating cause and effect. We conducted a controlled factorial experiment to assess the influence of non-medical factors on the diagnostic and treatment decisions made by practitioners of internal medicine in two common medical situations. METHOD: One hundred and ninety-two white male internists individually viewed professionally produced video scenarios in which the actor-patient, presenting with either chest pain or dyspnea, possessed various balanced combinations of sex, race, age, socioeconomic status, and health insurance coverage. Physician subjects were randomly drawn from lists of internists in private practice, hospital-based practice, and HMO's, at two levels of experience. RESULTS: The most frequent diagnoses for both chest pain and dyspnea were psychogenic origin and cardiac problems. Smoking cessation was the most frequent treatment recommendation for both conditions. Younger patients (all other factors being the same) were significantly more likely to receive the psychogenic diagnosis. Older patients were more likely to receive the cardiac diagnosis for chest pain, particularly if they were insured. HMO-based physicians were more likely to recommend a follow-up visit for chest pain. Several interactions of patient and physician factors were significant in addition to the main effects. CONCLUSIONS: The variability in decision-making evidenced by physicians in this experiment was not entirely accounted for by strictly rational Bayesian inference (the common prescriptive model for medical decision-making), in-as-much as non-medical factors significantly affected the decisions that they made. There is a need to supplement idealized medical schemata with considerations of social behavior in any comprehensive theory of medical decision-making.

Adult↗
PubMed1993

Exploring the relationship between rationality and bounded rationality in medical knowledge-based systems.

If our goal in Artificial Intelligence in Medicine (AIM) is to engineer systems health-care providers will both use and, in the process, improve their performance, we must concentrate on the development of causal theories of knowledge and problem solving. One broad direction in pursuing this goal is understanding the relationships between existing models of rationality and bounded rationality for similar tasks. Models of rationality refer to those approaches in which the optimal properties of the models are deductively provable, i.e. in which the processing is rational. Representative models of rationality used in AIM are deductive logical models, statistical models such as Bayesian inference models, and decision-analytic models. Models of bounded rationality are those which do not guarantee such optimal properties nor yield to deductive correctness proofs. These models have their roots in cognitive psychology. In this article we show how explicating the relationship between models of rationality and bounded rationality might be done in the case of abductive tasks in medicine. This is done by positioning these modeling approaches within the same framework (an abstract computational model) and interpreting in this context both computational complexity results concerning the nature of the task and empirical results studies of human problem-solving behavior.

Artificial Intelligence↗
PubMed2003

Apicoplast genome of the coccidian Eimeria tenella.

Unicellular apicomplexans possess an algal-originated plastid referred to as an apicoplast. Although apicomplexan parasites are comprised of highly diverse protists, the complete apicoplast genome sequences have only been determined from the hematozoan Plasmodium falciparum and cyst-forming coccidian Toxoplasma gondii. Here, we report the third complete sequence of apicoplast genome from the intestinal coccidian Eimeria tenella that may serve as a new drug target against coccidiosis in the livestock. The AT-rich E. tenella plastid genome is a 35-kb circular element. Its gene organization resembles more closely that of T. gondii than P. falciparum. Although the E. tenella plastid genome contains an almost identical set of genes to that found in P. falciparum and T. gondii, its encoded genes share low or moderate homologies with their counterparts in the other two apicomplexans. With the addition of this coccidian plastid genome sequence, we attempted to reexamine the apicoplast genome evolution and performed phylogenetic reconstructions using maximum likelihood and Bayesian inference (BI) methods based on a concatenated dataset of plastid-encoded rpoB, rpoC1 and rpoC2 proteins. All resulting rpo protein trees placed apicoplast as a sister to Euglena within the green lineage. On the other hand, many recent studies based on the organization of plastid genes and some nuclear-encoded plastid proteins have supported a common red algal ancestry of apicomplexan and dinoflagellate plastids. If the apicoplast indeed originated from a red ancestor, the green relationship of apicomplexan genes would probably imply that the ancestral host that gave rise to the (red) apicoplast might have already contained some primary green plastid genes.

Animals↗
PubMed2004

Phylogenetic relationships of discoglossid frogs (Amphibia:Anura:Discoglossidae) based on complete mitochondrial genomes and nuclear genes.

The complete nucleotide sequence of the mitochondrial (mt) genome was determined for three species of discoglossid frogs (Amphibia:Anura:Discoglossidae), representing three of the four recognized genera: Alytes obstetricans, Bombina orientalis, and Discoglossus galganoi. The organization and size of these newly determined mt genomes are similar to those previously reported for other vertebrates. Phylogenetic analyses (maximum likelihood, Bayesian inference, minimum evolution, and maximum parsimony) of mt protein-coding genes at the amino acid level were performed in combination with already published mt genome sequence data of three species of Neobatrachia, one of Pipoidea, and four of Caudata. Phylogenetic analyses based on the deduced amino acid sequences of all mt protein-coding genes arrived at the same topology. The monophyly of Discoglossidae is strongly supported. Within the Discoglossidae, Alytes is consistently recovered as sister group of Discoglossus, to the exclusion of Bombina. The three species representing Neobatrachia exhibited extremely long branches irrespective of the phylogenetic inference method used, and hence their relative position with respect to Discoglossidae and Xenopus may be artefactual due to a severe long branch attraction effect. To further investigate the phylogenetic intrarelationships of discoglossids, nucleotide sequences of four nuclear protein-coding genes (CXCR4, RAG1, RAG2, and Rhodopsin) with sequences available for the three discoglossid genera and Xenopus were retrieved from GenBank, and together with a concatenated nucleotide sequence data set containing all mt protein-coding genes except ND6 were subjected to separate and combined phylogenetic analyses. In all cases, a sister group relationship between Alytes and Discoglossus was recovered with high statistical support.

Amino Acid Sequence↗
PubMed2006

Structure and evolution of the mitochondrial control region and flanking sequences in the European cave salamander Proteus anguinus.

The European cave salamander Proteus anguinus Laurenti 1768 is one of the best-known subterranean animals, yet its evolutionary history and systematic relationships remain enigmatic. This is the first comprehensive study on molecular evolution within the taxon, using an mtDNA segment containing the control region (CR) and adjacent sequences. Two to seven tandem repeats of 24-32 bp were found in the intergenic spacer region (VNTR1), and three, four or six repeats, 59-77 bp each, in the 3' end of the CR (VNTR2). Different molecular mechanisms account for VNTR2 formation in different lineages of Proteus. The overall CR variation was lower than that of the spacer region, the 3' end of the cytb gene, or the tRNA genes. Individual genes and the concatenated non-repetitive sequences produced similar, well resolved maximum likelihood, Bayesian inference and parsimony trees. The numbers of repeat elements as well as the genealogy of the VNTR2 repeat units were mostly inconsistent with the groupings of the non-repetitive sequences. Different degrees of repeat array homogenization were detected in all major groups. Orthology was established for the first and the second VNTR2 elements of some populations. These two copies may therefore be used for analyses at the population level. The pattern of CR sequence variation points to strong genetic isolation of hydrographically separated populations. Genetic separation of the major groups of populations is incongruent with the current division into subspecies.

Animals↗
PubMed2005

A comparison of three modelling approaches for quantitative risk assessment using the case study of Salmonella spp. in poultry meat.

A comprehensive review of both the scientific literature and industry practices was undertaken to identify and quantify all sources of contamination throughout the entire poultry meat production chain by Salmonella spp. This information was used to develop a quantitative risk assessment (QRA) model for Salmonella in the production chain from the breeder farm to the chilled carcass. This was subsequently used as the basis on which to compare the merits of three approaches to QRA modelling in such systems. The original model used a Bayesian Network (BN). The second method was a Markov chain Monte Carlo (MCMC) approach, a numerical Bayesian technique which retained a similar network structure but allowed further development, such as the separation of variability and uncertainty. The third method was a more detailed simulation model. The BN responds immediately to changes, such as entering evidence, because it does not use simulation and can propagate information from any point in the network to all others by Bayesian inference. However, it requires all the variables to be discrete, which introduces errors if continuous variables have to be discretized. These errors can accumulate. The MCMC approach does not require discrete variables while retaining some of the properties of the BN model, such as the ability to draw inferences from evidence. Finally, the simulation offers greater flexibility, such as consideration of the individual carcass, but may be more complex to implement as a result and sacrifices the ability to propagate evidence.

Animals↗