PONDR-FIT: A meta-predictor of intrinsically disordered amino acids

Protein intrinsic disorder is becoming increasingly recognized in proteomics research. While lacking structure, many regions of disorder have been associated with biological function. There are many different experimental methods for characterizing intrinsically disordered proteins and regions; nevertheless, the prediction of intrinsic disorder from amino acid sequence remains a useful strategy especially for many large-scale proteomic investigations. Here we introduced a consensus artificial neural network (ANN) prediction method, which was developed by combining the outputs of several individual disorder predictors. By eight-fold cross-validation, this meta-predictor, called PONDR-FIT, was found to improve the prediction accuracy over a range of 3 to 20% with an average of 11% compared to the single predictors, depending on the datasets being used. Analysis of the errors shows that the worst accuracy still occurs for short disordered regions with less than ten residues, as well as for the residues close to order/disorder boundaries. Increased understanding of the underlying mechanism by which such meta-predictors give improved predictions will likely promote the further development of protein disorder predictors. Access to PONDR-FIT is available at www.disprot.org.     

Dentition in the African catfishes Andersonia (Amphiliidae) and Siluranodon (Schilbeidae) previously considered toothless

Based on light and scanning electron microscopic examination of their morphology, the dentition on both the premaxilla and dentary of Andersonia (Amphiliidae) and Siluranodon (Schilbeidae) catfishes is described from samples taken from tributaries of the White Nile in south‐western Ethiopia. These monotypic African genera were previously believed to lack teeth on the lower jaw in Andersonia and on both jaws in Siluranodon . Siluranodon exhibits an ontogenetic reduction: teeth were less frequently found in larger individuals than in smaller ones. In contrast to the adults of all other schilbeids, whose oral teeth are arranged in multiserial (or at least, biserial) bands, Siluranodon has uniserial teeth on both the premaxilla and the dentary. The adaptive, ontogenetic and phylogenetic aspects of jaw‐tooth reduction in catfishes are discussed.     

Species co-existence and character divergence across carnivores

Co-occurring species might be morphologically similar because they are adapted to the same environment, or morphologically dissimilar to minimize competition. We use sister species comparisons to evaluate the relationship between morphological disparity and regional patterns of co-occurrence across carnivores. Up to 63% of the variation in range overlap can be explained by morphological divergence in dentition. Species that differ more in carnassial tooth length overlap more in their geographical range. Carnassials are the primary teeth associated with food processing, and hence difference in carnassial size may be a good indicator of difference in resource use. We suggest this pattern is consistent with competition in sympatry driving ecological character displacement, or competitive exclusion among ecologically similar species. Our study uses newly available data on global distributions, morphology and phylogeny, and is the first to demonstrate a close relationship between morphological disparity and co-occurrence at a regional scale encompassing multiple communities.     

Making teeth to order: conserved genes reveal an ancient molecular pattern in paddlefish (Actinopterygii)

Ray-finned fishes (Actinopterygii) are the dominant vertebrate group today (+30 000 species, predominantly teleosts), with great morphological diversity, including their dentitions. How dental morphological variation evolved is best addressed by considering a range of taxa across actinopterygian phylogeny; here we examine the dentition of Polyodon spathula (American paddlefish), assigned to the basal group Acipenseriformes. Although teeth are present and functional in young individuals of Polyodon, they are completely absent in adults. Our current understanding of developmental genes operating in the dentition is primarily restricted to teleosts; we show that shh and bmp4, as highly conserved epithelial and mesenchymal genes for gnathostome tooth development, are similarly expressed at Polyodon tooth loci, thus extending this conserved developmental pattern within the Actinopterygii. These genes map spatio-temporal tooth initiation in Polyodon larvae and provide new data in both oral and pharyngeal tooth sites. Variation in cellular intensity of shh maps timing of tooth morphogenesis, revealing a second odontogenic wave as alternate sites within tooth rows, a dental pattern also present in more derived actinopterygians. Developmental timing for each tooth field in Polyodon follows a gradient, from rostral to caudal and ventral to dorsal, repeated during subsequent loss of teeth. The transitory Polyodon dentition is modified by cessation of tooth addition and loss. As such, Polyodon represents a basal actinopterygian model for the evolution of developmental novelty: initial conservation, followed by tooth loss, accommodating the adult trophic modification to filter-feeding.     

Towards better accuracy for missing value estimation of epistatic miniarray profiling data by a novel ensemble approach

Epistatic miniarray profiling (E-MAP) is a powerful tool for analyzing gene functions and their biological relevance. However, E-MAP data suffers from large proportion of missing values, which often results in misleading and biased analysis results. It is urgent to develop effective missing value estimation methods for E-MAP. Although several independent algorithms can be applied to achieve this goal, their performance varies significantly on different datasets, indicating different algorithms having their own advantages and disadvantages. In this paper, we propose a novel ensemble approach EMDI based on the high-level diversity to impute missing values that consists of two global and four local base estimators. Experimental results on five E-MAP datasets show that EMDI outperforms all single base algorithms, demonstrating an appropriate combination providing complementarity among different methods. Comparison results between several fusion strategies also demonstrate that the proposed high-level diversity scheme is superior to others. EMDI is freely available at www.csbio.sjtu.edu.cn/bioinf/EMDI/.     

The “Pithecanthropus IV” diastemata: Malocclusion in a fossil man

The Homo erectus skull fragments collected by von Koenigswald in Java in 1939 and designated by him as Pithecanthropus IV have been a source of ongoing interest because of the unique precence of seemingly simian-like precanine diastemata evident in the restored maxilla. These interdental spaces have posed a paradox because similar gaps are absent in other pithecanthropine remains and in considerably older hominid fossils.I have tested the hypothesis that the skull IV diastemata represent a human occlusal variant; in this paper, I illustrate methods of differential occlusal analysis and describe the multiplicity of factors that may lead to superficially similar maxillary precanine diastemata. Results of analysis of skull IV characteristics suggest that the diastemata were caused by labial displacement of the maxillary incisors because of vertical collapse after loss of the posterior mandibular teeth.     

Bioequivalence trials with the incomplete 3 x 3 crossover design

In bioequivalence trials, one often considers two or more generic products with the original one. The 3 x 3 crossover design can be adopted to evaluate the two generic candidates with a brand name drug, rather than conducting two separate 2 x 2 crossover trials. Dropouts, however, are more likely to occur due to various administrative reasons when we consider a higher order crossover design. A modified method, which was originally given by Chow and Shao (1997), is extended to compare two generic products with a reference in the incomplete 3 x 3 crossover design. A simulation study and discussion are also presented.