On the limitations of standard statistical modeling in biological systems: A full Bayesian approach for biology

One of the most important scientific challenges today is the quantitative and predictive understanding of biological function. Classical mathematical and computational approaches have been enormously successful in modeling inert matter, but they may be inadequate to address inherent features of biological systems. We address the conceptual and methodological obstacles that lie in the inverse problem in biological systems modeling. We introduce a full Bayesian approach (FBA), a theoretical framework to study biological function, in which probability distributions are conditional on biophysical information that physically resides in the biological system that is studied by the scientist.     

Robust joint modeling of longitudinal measurements and time to event data using normal/independent distributions: A Bayesian approach

Joint modeling of longitudinal data and survival data has been used widely for analyzing AIDS clinical trials, where a biological marker such as CD4 count measurement can be an important predictor of survival. In most of these studies, a normal distribution is used for modeling longitudinal responses, which leads to vulnerable inference in the presence of outliers in longitudinal measurements. Powerful distributions for robust analysis are normal/independent distributions, which include univariate and multivariate versions of the Student's t, the slash and the contaminated normal distributions in addition to the normal. In this paper, a linear‐mixed effects model with normal/independent distribution for both random effects and residuals and Cox's model for survival time are used. For estimation, a Bayesian approach using Markov Chain Monte Carlo is adopted. Some simulation studies are performed for illustration of the proposed method. Also, the method is illustrated on a real AIDS data set and the best model is selected using some criteria.     

A kinematic method for computing the motion of the body centre-of-mass (CoM) during walking: a Bayesian approach

The gait pattern of a particular patient can be altered in a large set of pathologies. Tracking the body centre-of-mass (CoM) during the gait allows a quantitative evaluation of these diseases at comparing the gait with normal patterns. A correct estimation of this variable is still an open question because of its non-linearity and inaccurate location. This paper presents a novel strategy for tracking the CoM, using a biomechanical gait model whose parameters are determined by a Bayesian strategy. A particle filter is herein implemented for predicting the model parameters from a set of markers located at the sacral zone. The present approach is compared with other conventional tracking methods and decreases the calculated root mean squared error in about a 56% in the x-axis and 59% in the y-axis.     

BGX: a fully Bayesian integrated approach to the analysis of Affymetrix GeneChip data

We present Bayesian hierarchical models for the analysis of Affymetrix GeneChip data. The approach we take differs from other available approaches in two fundamental aspects. Firstly, we aim to integrate all processing steps of the raw data in a common statistically coherent framework, allowing all components and thus associated errors to be considered simultaneously. Secondly, inference is based on the full posterior distribution of gene expression indices and derived quantities, such as fold changes or ranks, rather than on single point estimates. Measures of uncertainty on these quantities are thus available. The models presented represent the first building block for integrated Bayesian Analysis of Affymetrix GeneChip data: the models take into account additive as well as multiplicative error, gene expression levels are estimated using perfect match and a fraction of mismatch probes and are modeled on the log scale. Background correction is incorporated by modeling true signal and cross-hybridization explicitly, and a need for further normalization is considerably reduced by allowing for array-specific distributions of nonspecific hybridization. When replicate arrays are available for a condition, posterior distributions of condition-specific gene expression indices are estimated directly, by a simultaneous consideration of replicate probe sets, avoiding averaging over estimates obtained from individual replicate arrays. The performance of the Bayesian model is compared to that of standard available point estimate methods on subsets of the well known GeneLogic and Affymetrix spike-in data. The Bayesian model is found to perform well and the integrated procedure presented appears to hold considerable promise for further development.     

GEFs, GAPs, GDIs and effectors: taking a closer (3D) look at the regulation of Ras-related GTP-binding proteins

Cell biology depends on the interactions of macromolecules, such as protein—DNA, protein—protein or protein—nucleotide interactions. GTP-binding proteins are no exception to the rule. They regulate cellular processes as diverse as protein biosynthesis and intracellular membrane trafficking. Recently, a large number of genes encoding GTP-binding proteins and the proteins that interact witht these molecular switches have been cloned and expressed. The 3D structures of some of these have also been elucidated     

Quantification and distribution of a Tetragonula carbonaria swarm (Hymenoptera: Apidae)

Manual mark-by-mark image analysis was used to quantify the number of individuals present in a Tetragonula carbonaria swarm. A total of 7328 bees were identified in the swarm. The distribution of individuals within the swarm followed a Gaussian distribution, with the distances to the nearest neighbour strongly positively skewed. The clustering of bees in the centre of the swarm is likely a mechanism for reducing predation risk. In the case of male mating swarms, large aggregations may increase the mating success of the species.     

A molecular approach to the phylogenetic relationships of the western palaearctic Helicoidea (Gastropoda: Stylommatophora)

Molecular phylogenetic relationships among 45 members of the Helicoidea (Gastropoda: Stylommatophora) were examined using partial mitochondrial 16S rRNA sequences. Phylogenetic relationships were inferred using maximum parsimony, maximum likelihood and Bayesian methods. The reconstructed phylogenies showed a good degree of support for more recent branches, but gave little support to deeper nodes. Mitochondrial rDNA data further confirmed monophyletic status of helicids, recognized monachine hygromiid and bradybaenid clades and resolved a number of relationships in the helicelline hygromiids. With the respect to the latter assemblage, most of the anatomically based groups are confirmed, corroborating the diagnostic value of the dart-sac complex and a close affinity between Ichnusomunda sacchii and species of the genus Cernuella . Nevertheless, some well resolved branches challenge previous systematic arrangements, grouping species previously placed in different arrangements. In particular, support was not found for the monophyly of helicelline hygromiids with pedal penial innervation. Possible explanations for these incongruencies are suggested. 16S sequence data are appropriate for studies of relationships within the different species groups and less so for recovery of more ancient radiations in the Helicoidea. It will be valuable to combine the 16S data with other gene sequences to estimate basal relationships.  © 2005 The Linnean Society of London, Biological Journal of the Linnean Society , 2005, 85 , 501–512.     

Predicting the distribution of a rare species of moss: The case of Buxbaumia viridis (Bryopsida,Buxbaumiaceae)

Buxbaumia viridis is a rare policy species restricted to decaying woods in forests. Although Member States of EU are required to monitor its conservation status, specific models able to predict species distribution are still lacking. However, the availability of such models would strongly improve the efficiency in collection additional data and consequently lead to a better knowledge of its ecology. Aims of this work were (i) to provide a model for species distribution assessing the importance of different environmental variables thought to be important in setting the occurrence of Buxbaumia viridis and (ii) to test the effect of imperfect detection in defining the environmental space where the species occur. With this work, records of B. viridis increased twofold in the Alpine region of Italy, passing from 13 records to 26. We showed that on the Alps, occurrence of Buxbaumia viridis was best predicted by northness, rainfall, canopy closure and necromass. Necromass was the single most important variable. A volume of 48–61 m³/ha of necromass was identified as the threshold value determining the high probability of species occurrence. The imperfect detection probability of the species (p = 0.25), biased towards zero the importance of the environmental variables.     

A new look at geographic and phylogenetic relationships within the species group surrounding Octopus vulgaris (Mollusca, Cephalopoda): indications of very wide distribution from mitochondrial DNA sequences

The distribution of Octopus vulgaris has not yet been completely clarified. For a long time, a cosmopolitan distribution with unknown distribution limits had been assumed. This assumption has recently been questioned and it has been postulated that the distribution is restricted to the Mediterranean and the northeastern Atlantic. However, as our previous studies show, the existence of O. vulgaris can be confirmed for the Mediterranean and the whole eastern Atlantic, and evidence is provided for its occurrence in the western Atlantic. The aim of the present work is to extend our previous data matrix and to clarify whether O. vulgaris exists in the northwestern Pacific. Therefore, the sequence variation in ostensible O. vulgaris from 13 localities in the Mediterranean (France), the Atlantic Ocean [Lanzarote, Senegal, South Africa (Atlantic, Indian Ocean), Tristan da Cunha, north, middle and south Brazil], the Caribbean Sea (Venezuela) and the Pacific Ocean (Taiwan, Japan and Costa Rica) was examined using the mitochondrial genes coding for the 16S rRNA and cytochrome oxidase subunit III (COIII). Sequence divergence was relatively low between populations of O. vulgaris from the Mediterranean, the eastern and western Atlantic (except north Brazil), Venezuela, Taiwan and Japan compared with other species of the genus Octopus . Trees constructed by using maximum likelihood, neighbour joining and maximum parsimony algorithms (PAUP) show the above-mentioned populations from the Mediterranean, the western and eastern Atlantic, Venezuela and the northwestern Pacific (Japan and Taiwan) as a monophyletic cluster. Thus, even if the Octopus vulgaris -like octopus from north Brazil should turn out a cryptic species, the data of this work not only support our hypothesis of the distribution of O. vulgaris in the Mediterranean, the eastern and western Atlantic but also show that O. vulgaris is present in the northwestern Pacific, namely in the waters of Taiwan and Japan.     

A hierarchical Bayesian Beta regression approach to study the effects of geographical genetic structure and spatial autocorrelation on species distribution range shifts

Global climate change (GCC) may be causing distribution range shifts in many organisms worldwide. Multiple efforts are currently focused on the development of models to better predict distribution range shifts due to GCC. We addressed this issue by including intraspecific genetic structure and spatial autocorrelation (SAC) of data in distribution range models. Both factors reflect the joint effect of ecoevolutionary processes on the geographical heterogeneity of populations. We used a collection of 301 georeferenced accessions of the annual plant Arabidopsis thaliana in its Iberian Peninsula range, where the species shows strong geographical genetic structure. We developed spatial and nonspatial hierarchical Bayesian models (HBMs) to depict current and future distribution ranges for the four genetic clusters detected. We also compared the performance of HBMs with Maxent (a presence‐only model). Maxent and nonspatial HBMs presented some shortcomings, such as the loss of accessions with high genetic admixture in the case of Maxent and the presence of residual SAC for both. As spatial HBMs removed residual SAC, these models showed higher accuracy than nonspatial HBMs and handled the spatial effect on model outcomes. The ease of modelling and the consistency among model outputs for each genetic cluster was conditioned by the sparseness of the populations across the distribution range. Our HBMs enrich the toolbox of software available to evaluate GCC‐induced distribution range shifts by considering both genetic heterogeneity and SAC, two inherent properties of any organism that should not be overlooked.     

A molecular phylogenetic analysis of the "true thrushes" (Aves: Turdinae)

The true thrushes (Passeriformes: Muscicapidae, subfamily Turdinae) are a speciose and widespread avian lineage presumed to be of Old World origin. Phylogenetic relationships within this assemblage were investigated using mitochondrial DNA (mtDNA) sequence data that included the cytochrome b and ND2 genes. Our ingroup sampling included 54 species representing 17 of 20 putative turdine genera. Phylogenetic trees derived via maximum parsimony and maximum likelihood were largely congruent. Most of the Turdine taxa sampled can be placed into one of six well supported clades. Our data indicate a polyphyletic Zoothera which can be divided into at least two (Afro-Asian and Austral-Asian) main clades. The genus Turdus, as presently recognized, is paraphyletic but forms a well supported clade with the addition of three mostly monotypic genera (Platycichla, Nesocichla, and Cichlherminia). We identify an exclusively New World clade that includes a monophyletic Catharus, Hylocichla, Cichlopsis, Entomodestes, Ridgwayia, and Ixoreus. Members of the morphologically and behaviorally distinct genera Sialia, Myadestes, and Neocossyphus unexpectedly form a basal clade. Using multiple outgroup choices, we show that this group is distantly related, but unequivocally the sister group to the remaining Turdines sampled. The Turdinae appear to be a relatively old songbird lineage, originating in the mid to late Miocene. If the Turdinae are indeed Old World in origin, our data indicate a minimum of three separate invasions of the New World.     

A kinematic method for computing the motion of the body centre-of-mass (CoM) during walking: a Bayesian approach

The gait pattern of a particular patient can be altered in a large set of pathologies. Tracking the body centre-of-mass (CoM) during the gait allows a quantitative evaluation of these diseases at comparing the gait with normal patterns. A correct estimation of this variable is still an open question because of its non-linearity and inaccurate location. This paper presents a novel strategy for tracking the CoM, using a biomechanical gait model whose parameters are determined by a Bayesian strategy. A particle filter is herein implemented for predicting the model parameters from a set of markers located at the sacral zone. The present approach is compared with other conventional tracking methods and decreases the calculated root mean squared error in about a 56% in the x-axis and 59% in the y-axis.     

Accounting for phylogenetic uncertainty in biogeography: a Bayesian approach to dispersal-vicariance analysis of the thrushes (Aves: Turdus)

The phylogeny of the thrushes (Aves: Turdus) has been difficult to reconstruct due to short internal branches and lack of node support for certain parts of the tree. Reconstructing the biogeographic history of this group is further complicated by the fact that current implementations of biogeographic methods, such as dispersal-vicariance analysis (DIVA; Ronquist, 1997), require a fully resolved tree. Here, we apply a Bayesian approach to dispersal-vicariance analysis that accounts for phylogenetic uncertainty and allows a more accurate analysis of the biogeographic history of lineages. Specifically, ancestral area reconstructions can be presented as marginal distributions, thus displaying the underlying topological uncertainty. Moreover, if there are multiple optimal solutions for a single node on a certain tree, integrating over the posterior distribution of trees often reveals a preference for a narrower set of solutions. We find that despite the uncertainty in tree topology, ancestral area reconstructions indicate that the Turdus clade originated in the eastern Palearctic during the Late Miocene. This was followed by an early dispersal to Africa from where a worldwide radiation took place. The uncertainty in tree topology and short branch lengths seems to indicate that this radiation took place within a limited time span during the Late Pliocene. The results support the role of Africa as a probable source area for intercontinental dispersals as suggested for other passerine groups, including basal diversification within the songbird tree.     

The evolution of ecomorphological traits within the Abrothrichini (Rodentia: Sigmodontinae): a Bayesian phylogenetics approach

The generally accepted hypothesis regarding the origin of fossorial mammals proposes adaptive convergence from open environments towards the use of subterranean environments. We evaluated this hypothesis for South American mole-mice using conventional and Bayesian frameworks, with independent evidence. By using a molecular approach based on Cytochrome b and IRBP sequences, we evaluated phylogenetic relationships, time of origin, the ancestral trait of fossoriality, and ancestral distributions of species belonging to the Andean Clade (Rodentia: Sigmodontinae). Our results indicate that the Andean Clade is highly sustained; with one clade grouping all fossorial forms and another grouping all cursorial species. We hypothesized that fossoriality originated in the Miocene/Pliocene transition, in the Temperate Forests of southern South America. We conclude that the origin of fossorial ecomorphological traits did not necessarily occur under a general model of open environments, the origin of these traits depends on the ecological-historical relationship of the taxon with the environment.     

Colonization history of the Swiss Rhine basin by the bullhead (Cottus gobio): inference under a Bayesian spatially explicit framework

The present distribution of freshwater fish in the Alpine region has been strongly affected by colonization events occurring after the last glacial maximum (LGM), some 20 000 years ago. We use here a spatially explicit simulation framework to model and better understand their colonization dynamics in the Swiss Rhine basin. This approach is applied to the European bullhead ( Cottus gobio ), which is an ideal model organism to study fish past demographic processes since it has not been managed by humans. The molecular diversity of eight sampled populations is simulated and compared to observed data at six microsatellite loci under an approximate Bayesian computation framework to estimate the parameters of the colonization process. Our demographic estimates fit well with current knowledge about the biology of this species, but they suggest that the Swiss Rhine basin was colonized very recently, after the Younger Dryas some 6600 years ago. We discuss the implication of this result, as well as the strengths and limits of the spatially explicit approach coupled to the approximate Bayesian computation framework.