Fast computation of distance estimators

Background  

Some distance methods are among the most commonly used methods for reconstructing phylogenetic trees from sequence data. The input to a distance method is a distance matrix, containing estimated pairwise distances between all pairs of taxa. Distance methods themselves are often fast, e.g., the famous and popular Neighbor Joining (NJ) algorithm reconstructs a phylogeny of n taxa in time O(n ³). Unfortunately, the fastest practical algorithms known for Computing the distance matrix, from n sequences of length l, takes time proportional to l·n ². Since the sequence length typically is much larger than the number of taxa, the distance estimation is the bottleneck in phylogeny reconstruction. This bottleneck is especially apparent in reconstruction of large phylogenies or in applications where many trees have to be reconstructed, e.g., bootstrapping and genome wide applications.     

Fermentation analysis by clustering

To supervise, stabilize and optimize antibiotic fermentations in the industrial scale expert systems are presently worked out. For the knowledge acquisition various classifiers are tested using a set of 27 nourseothricin fermentation runs. Two methods are applied: optimal clustering by help of minimum variance criterion and hierarchical clustering by help of dendrograms. The fermentations are classified with respect to the specific material costs as well as the product formation kinetics.List of Symbols a kg/m³ initial value of linearized product kinetics - b kg/(m³ · h) slope of linearized product kinetics - B binary variable (value 0 or 1) - C DM/kg specific costs - d distance - m number of samples - p kg/m³ product concentration - pO₂ % dissolved oxygen concentration - t h fermentation time - T h initial time of linearized product kinetics - n number of fermentation runs     

EDENetworks: A user‐friendly software to build and analyse networks in biogeography,ecology and population genetics

The recent application of graph‐based network theory analysis to biogeography, community ecology and population genetics has created a need for user‐friendly software, which would allow a wider accessibility to and adaptation of these methods. EDENetworks aims to fill this void by providing an easy‐to‐use interface for the whole analysis pipeline of ecological and evolutionary networks starting from matrices of species distributions, genotypes, bacterial OTUs or populations characterized genetically. The user can choose between several different ecological distance metrics, such as Bray‐Curtis or Sorensen distance, or population genetic metrics such as F_ST or Goldstein distances, to turn the raw data into a distance/dissimilarity matrix. This matrix is then transformed into a network by manual or automatic thresholding based on percolation theory or by building the minimum spanning tree. The networks can be visualized along with auxiliary data and analysed with various metrics such as degree, clustering coefficient, assortativity and betweenness centrality. The statistical significance of the results can be estimated either by resampling the original biological data or by null models based on permutations of the data.     

An optimal algorithm to reconstruct trees from additive distance data

In this article the question of reconstructing a phylogeny from additive distance data is addressed. Previous algorithms used the complete distance matrix of then OTUs (Operational Taxonomic Unit), that corresponds to the tips of the tree. This usedO(n ²) computing time. It is shown that this is wasteful for biologically reasonable trees. If the tree has internal nodes with degrees that are bounded onO(n*log(n)) algorithm is possible. It is also shown if the nodes can have unbounded degrees the problem hasn ² as lower bound.     

An unstructured kinetic model to study NaCl effect on volatile ester fermentation by <Emphasis Type="Italic">Candida etchellsii</Emphasis> for soy sauce production

Salt-tolerant aromatic yeast is an important microorganism arising from the solid state fermentation of soy sauce. The fermentation kinetics of volatile esters by Candida etchellsii was studied in a batch system. The data obtained from the fermentation were used for determining the kinetic parameters of the model. Batch experimental results at four NaCl levels (180, 200, 220, and 240 g/L) were used to formulate the parameter estimation model. The kinetic parameters of the model were optimized by specifically designed Runge-Kutta Genetic Algorithms (GA). The resulting mathematical model for volatile ester production, cell growth and glucose consumption simulates the experimental data well. The resulting new model was capable of explaining the behavior of volatile ester fermentation. The optimized parameters (μ_o, X _max, K _i, α, β, Y _X/S, m, and Y _P/S) were characterized by a correlation of functions assuming salinity dependence. The kinetic models optimized by GA describe the batch fermentation process adequately, as demonstrated by our experimental results.     

Production and properties of three pectinolytic activities produced byAspergillus niger in submerged and solid-state fermentation

Three extracellular pectinases were produced byAspergillus niger CH4 by submerged and solid-state fermentation, and their physicochemical and kinetic properties were studied. The highest productivities of endo- and exo-pectinase and pectin lyase were obtained with solid-state fermentation. The kinetic and physicochemical properties of these enzymes were influenced by the type of culture method used. All activities were very different in terms of pH and temperature optima, stability at different pH and temperature values and affinity for the substrate (K _m values). In solid-state fermentation, all pectinase activities were more stable at extreme pH and temperature values but theK _m values of endo-pectinase and pectin lyase were higher with respect to those activities obtained by the submerged-culture technique. The pectin lyase activity obtained by the submerged-culture technique showed substrate inhibition but the enzyme obtained by solid-state fermentation did not. Electrophoresis, using sodium dodecyl sulphate/polyacrylamide gel with enzymatic extracts obtained for both culture methods, showed the same number on protein bands but some differences were found in their electrophoretic position. The results obtained in this work suggest that the culture method (submerged or solid-state) may be responsible for inducing changes in some of the pectinolytic enzymes produced byA. niger.     

Strong Patterns in Homooligomer Tracts Occurrences in Non-Coding and in Potential Regulatory Sites in Eukaryotic Genomes

Abstract

Previous studies of the dinucleotides flanking both the 5′ and 3′ ends of homooligomer tracts have shown that some flanks are consistently preferred over others (1,2). In the first preferred group, the homooligomer tracts are flanked by the same nucleotide and/or the complementary nucleotides, e.g., ATA_n, TTA_n, CCG_n, where n=2–5. Runs flanked by nucleotides with which they cannot base pair are distinctly disfavored. (In this group A/T_n are flanked by C and/or G; G_n/C_n are flanked by A/T, e.g., CGA_n, T_nGG, G., AT). The frequencies of runs flanked by AorT, and G or C (“mixed” group) are as expected. Here we seek the origin of this effect and its relevance to protein-DNA interactions. Surprisingly, within the first group, runs flanked by their complements with a pyrimidine-purine junction (e.g., TTA_n, C_nGG) are greatly preferred. The frequencies of their purine-pyrimidine junction mirror-images is just as expected. This effect, as well as additional ones enumerated below, is seen universally in eukaryotes and in prokaryotes, although it is stronger in the former. Detailed analysis of regulatory regions shows these strong trends, particularly in GC sequences. The potential relationship to DNA conformation and DNA-protein interaction is discussed.     

Vergleich von Messungen des kLa-Wertes nach der stationären und der dynamischen Methode bei der Fermentation von L-Lysin und Turimycin

The calculation and scale-up of fermentation processes need k_La as one of the most important engineering data. There are two methods to determine k_La depending on power input, aeration rate and the properties of the fermentation broth: static with a balance between air supply and exit, dynamic gassing out with following the changes of dissolved oxygen concentration during periods of air off and a following air on. Within early intervals of fermentation time the data from both methods agree well, while for later time intervals the dynamic method always gives much lower values for k_La than static. The only explanations for this phenomenon are quick changes in the oxygen metabolism or an enzymatic storage of oxygen. For both gassing out and saturation period it is possible to calculate the same absolute amounts of this additional oxygen.     

Kinetics of the electron transfer reaction of Cytochrome <Emphasis Type="Italic">c</Emphasis><Subscript>552</Subscript> adsorbed on biomimetic electrode studied by time-resolved surface-enhanced resonance Raman spectroscopy and electrochemistry

Cytochrome c ₅₅₂ (Cyt-c ₅₅₂) and its redox partner ba ₃ -oxidase from Thermus thermophilus possess structural differences compared with Horse heart cytochrome c (cyt-c)/cytochrome c oxidase (CcO) system, where the recognition between partners and the electron transfer (ET) process is initiated via electrostatic interactions. We demonstrated in a previous study by surface-enhanced resonance Raman (SERR) spectroscopy that roughened silver electrodes coated with uncharged mixed self-assembled monolayers HS–(CH₂) _n –CH₃/HS–(CH₂) _{n + 1}–OH 50/50, n = 5, 10 or 15, was a good model to mimic the Cyt-c ₅₅₂ redox partner. All the adsorbed molecules are well oriented on such biomimetic electrodes and transfer one electron during the redox process. The present work focuses on the kinetic part of the heterogeneous ET process of Cyt-c ₅₅₂ adsorbed onto electrodes coated with such mixed SAMs of different alkyl chain length. For that purpose, two complementary methods were combined. Firstly cyclic voltammetry shows that the ET between the adsorbed Cyt-c ₅₅₂ and the biomimetic electrode is direct and reversible. Furthermore, it allows the estimation of both the density surface coverage of adsorbed Cyt-c ₅₅₂ and the kinetic constants values. Secondly, time-resolved SERR (TR-SERR) spectroscopy showed that the ET process occurs without conformational change of the Cyt-c ₅₅₂ heme group and allows the determination of kinetic constants. Results show that the kinetic constant values obtained by TR-SERR spectroscopy could be compared to those obtained from cyclic voltammetry. They are estimated at 200, 150 and 40 s⁻¹ for the ET of Cyt-c ₅₅₂ adsorbed onto electrodes coated with mixed SAMs HS–(CH₂) _n –CH₃/HS–(CH₂) _{n + 1}–OH 50/50, n = 5, 10 or 15, respectively. Presented at the joint biannual meeting of the SFB-GEIMM-GRIP, Anglet France, 14–19 October, 2006.     

Dynamical machinery of a biochemical clock

Closed positive feedback loops of catalytic reactions between macromolecules, or hypercycles, provide a kinetic mechanism whereby each Species serves to catalyze selfreproduction of its successor in the loop. Hypercycles of five members or more evolve into limit cycles characteristic of a biochemical clock. Computer study of the coupled non-linear differential equations which describe these systems shows that the periodT _n of then-species limit cycle is given byT _n=nτ_n, where τ_n is an elemental repeat period reflecting translational time invariance. Analytic solutions of the equations are developed so that the time evolution of elementaryn-hypercycles can be traced in dynamical detail. It is shown that the magnitude of τ_n is, to good approximation, a linear function ofn. For a givenn, τ_n is a very sensitive function of the relative concentration a given member of the loop has at the time its predecessor dominates the state of the hypercycle. These concentrations decrease with increasingn. Aroundn=15 they become so small that elementary hypercycles become unstable against disruptive concentration fluctuations. Species concentrations for more realistic hypercycles tend not to be as small, so that the present estimate of a maximum number of components is a lower bound.     

The relative power of genome scans to detect local adaptation depends on sampling design and statistical method

Although genome scans have become a popular approach towards understanding the genetic basis of local adaptation, the field still does not have a firm grasp on how sampling design and demographic history affect the performance of genome scans on complex landscapes. To explore these issues, we compared 20 different sampling designs in equilibrium (i.e. island model and isolation by distance) and nonequilibrium (i.e. range expansion from one or two refugia) demographic histories in spatially heterogeneous environments. We simulated spatially complex landscapes, which allowed us to exploit local maxima and minima in the environment in ‘pair’ and ‘transect’ sampling strategies. We compared F_ST outlier and genetic–environment association (GEA) methods for each of two approaches that control for population structure: with a covariance matrix or with latent factors. We show that while the relative power of two methods in the same category (F_ST or GEA) depended largely on the number of individuals sampled, overall GEA tests had higher power in the island model and F_ST had higher power under isolation by distance. In the refugia models, however, these methods varied in their power to detect local adaptation at weakly selected loci. At weakly selected loci, paired sampling designs had equal or higher power than transect or random designs to detect local adaptation. Our results can inform sampling designs for studies of local adaptation and have important implications for the interpretation of genome scans based on landscape data.     

The association reaction of collagen model polypeptides (Pro-Pro-Gly)n

The characterization of recently synthesized (Pro-Pro-Gly)_n, n = 7, 8 is described, along with melting profile studies of its association equilibrium, and thermal quenching studies of the kinetics of its association reaction. The order of the kinetic reaction is about 3, implying that three peptide chains are involved in the activated state of the rate-limiting step. The reaction rate was found to exhibit a negative temperature coefficient. With the (Pro-Pro-Gly)₇ peptide, the concentration dependence of the (Pro-Pro-Gly)_n association equilibrium was observed for the first time. Detailed thermodynamic analysis for these n = 7, 8 data, together with literature data for n = 10, 15, 20 were carried out for both the simple “all-or-none” binding model and for a series of complex equilibrium models. For the latter, all of the (Pro-Pro-Gly)_n data (in 10% acetic acid) are fit best with a maximally cooperative near-neighbor model with a standard enthalpy change ΔH = ?650 cal/mole of residues, and a standard entropy change ΔS = ?14.63 ?10/n cal/deg-mole of residues, wherein the ?10 eu represents an end-effect contribution to the binding free energy. With regard to optical rotatory properties and thermodynamic parameters, the data for the new n = 7, 8 peptides match rather well with the literature data for the n = 10, 15, and 20 peptides. The enthalpic stabilization per residue of the triple-helical form of (Pro-Pro-Gly)_n was nearly an order of magnitude smaller than the enthalpic stabilization per additional proline obtained from direct calorimetric measurements on native collagens of different (and much lower) proline contents by Privalov and Tiktopulo. [Biopolymers (1970) 9 , 127–139.] Possible explanations for this phenomenon are discussed.     

Fractional Plans to Estimate Main Effects and Two Factor Interactions Inclusive of a Specific Factor

Balanced incomplete block designs are used to construct non‐geometric 2ⁿ fractional factorial plans to estimate all n main effects and n – 1, 2 factor interactions with a specific factor included in each interaction. When the balanced incomplete block design is of Family (A), the resulting fractional factorial plan has the same number of runs as a fold‐over Hadamard matrix giving same variances for the estimates; however, some new designs are shown to be non‐isomorphic to the fold‐over Hadamard matrix plans.     

A Study on the Synthetic Characteristics of the Extracellular Polysaccharide (EPS) of Ganoderma lucidum Cultured in Batch Fermentation Using a Kinetic Model

The synthetic characteristics of the extracellular polysaccharide (EPS) of Ganoderma lucidum in batch fermentation were studied. The result showed that the production of EPS was partially growth-associated. The cell dry weight (CDW) and EPS reached 15.56 g·L⁻¹ and 3.02 g·L⁻¹, respectively. The yield of EPS to cell dry weight (Y_p/x) was 0.19. On the basis of the test results of batch fermentation, a kinetic model was proposed by using the Logistic equation for cell growth, the Luedeking–Piret equation for EPS production, and the Luedeking-piret-like equation for the consumption of glucose as substrate. The calculated results using these models were satisfactorily compared with the experimental data under various concentrations of glucose, and the average of relative errors was found to be not more than 5%. The kinetic model had practical guidance interesting in producing PES by Ganoderma lucidum.     

Modeling of growth and lactate fermentation by Lactococcus lactis subsp. lactis biovar. diacetylactis in batch culture

The kinetic behaviour of Lactococcus lactis subsp. lactis biovar. diacetylactis was studied in batch culture under non-limiting conditions that allow high growth and product formation. A model based on laboratory results is proposed for growth and l-lactate fermentation. It shows the necessity for differentiating biomass into three physiological states, two active, X_g (growth + acidification) and X_ng (acidification), and one inactive, X_i. The kinetic theory of the model demonstrates the non-competitive nature of fermentation end-product inhibition on growth and acidification, and describes the passage from one physiological state to another. Satisfying simulations were obtained for batch fermentations, and the use of this type of model for determining and optimizing fermentation parameters is discussed. Correspondence to: C. Diviès     

An energetic evaluation of a "Smith" collagen microfibril model.

An energy minimized three-dimensional structure of a collagen microfibril template was constructed based on the five-stranded model of Smith (1968), using molecular modeling methods and Kollman force fields (Weiner and Kollman, 1981). For this model, individual molecules were constructed with three identical polypeptide chains ((Gly-Pro-Pro) _n , (Gly-Prop-Hyp) _n , or (Gly-Ala-Ala) _n , wheren=4, 12, and 16) coiled into a right-handed triple-helical structure. The axial distance between adjacent amino acid residues is about 0.29 nm per polypeptide chain, and the pitch of each chain is approximately 3.3 residues. The microfibril model consists of five parallel triple helices packed so that a left-handed superhelical twist exists. The structural characteristics of the computed microfibril are consistent with those obtained for collagen by X-ray diffraction and electron microscopy. The energy minimized Smith microfibril model for (Gly-Pro-Pro)₁₂ has an axial length of about 10.2 nm (for a 36 amino acid residue chain), which gives an estimated D-spacing (234 amino acids per chain) of approximately 66.2 nm. Studies of the microfibril models (Gly-Pro-Pro)₁₂, (Gly-Pro-Hyp)₁₂, and (Gly-Ala-Ala)₁₂ show that nonbonded van der Waals interactions are important for microfibril formation, while electrostatic interactions contribute to the stability of the microfibril structure and determine the specificity by which collagen molecules pack within the microfibril.     

灵芝胞外多糖分批发酵动力学模型

利用分批发酵研究了灵芝(Ganoderma lucidum)胞外多糖的合成特性,结果表明Ganodermalucidum多糖合成和菌体生长呈部分生长关联型。菌体干重、胞外多糖分别达到15.56g·L-1、3.02g·L-1,胞外多糖对细胞干重得率系数(Yp/x)为0.19。根据分批发酵试验结果采用Logistic方程、Luedeking-Piret方程和类似Luedeking-Piret方程,得到了描述灵芝生长、胞外多糖以及葡萄糖底物消耗分批发酵动力学模型。同时在初始葡萄糖变化较大范围内,试验数据与模型预测值进行了比较拟合,平均相对误差小于5%,表现出很好的适用性。表明该动力学模型对指导灵芝胞外多糖的发酵生产具有实际意义。     

灵芝胞外多糖分批发酵动力学模型

利用分批发酵研究了灵芝（Ganoderma lucidum）胞外多糖的合成特性,结果表明Ganoderma lucidum多糖合成和菌体生长呈部分生长关联型。菌体干重、胞外多糖分别达到15.56g·L^-1<、3.02g·L^-1<,胞外多糖对细胞干重得率系数(Y_p/x）为0.19。根据分批发酵试验结果采用Logistic方程、Luedeking-Piret方程和类似Luedeking-Piret方程,得到了描述灵芝生长、胞外多糖以及葡萄糖底物消耗分批发酵动力学模型。同时在初始葡萄糖变化较大范围内,试验数据与模型预测值进行了比较拟合,平均相对误差小于5％,表现出很好的适用性。表明该动力学模型对指导灵芝胞外多糖的发酵生产具有实际意义。     

<Emphasis Type="Italic">Scoredist</Emphasis>: A simple and robust protein sequence distance estimator

Background  

Distance-based methods are popular for reconstructing evolutionary trees thanks to their speed and generality. A number of methods exist for estimating distances from sequence alignments, which often involves some sort of correction for multiple substitutions. The problem is to accurately estimate the number of true substitutions given an observed alignment. So far, the most accurate protein distance estimators have looked for the optimal matrix in a series of transition probability matrices, e.g. the Dayhoff series. The evolutionary distance between two aligned sequences is here estimated as the evolutionary distance of the optimal matrix. The optimal matrix can be found either by an iterative search for the Maximum Likelihood matrix, or by integration to find the Expected Distance. As a consequence, these methods are more complex to implement and computationally heavier than correction-based methods. Another problem is that the result may vary substantially depending on the evolutionary model used for the matrices. An ideal distance estimator should produce consistent and accurate distances independent of the evolutionary model used.     

Cytotaxonomy in distinct populations of Hoplias aff. malabaricus (Characiformes,Erythrinidae) from lower Paranapanema River basin

Cytogenetic and morphometric analyses were carried out in Hoplias aff. malabaricus specimens from six distinct populations from the lower Paranapanema River basin, located between the states of Paraná and São Paulo, Brazil. Measurements were also taken from a specimen collected in Surinam. In a population from a fish farm station at Universidade do Norte do Parana (EPUNOPAR), two sympatric cytotypes (2n = 40 and 2n = 42 chromosomes) are found. A population from a fish farm station at Universidade Estadual de Londrina (EPUEL) shows 2n = 42 meta–submetacentric chromosomes for males and females with a simple sex chromosome system of XX/XY type. Populations from the Vermelho and Rancho Alegre Rivers, Três Bocas Stream and Paranapanema River have 2n = 39 chromosomes in males and 2n = 40 chromosomes in females, showing a multiple sex chromosome system of X₁X₁X₂X₂/X₁X₂Y type. Twenty morphological variables were studied. These measurements were used for an analysis of the canonical variables and standard analysis of proportional measurements. The most variable measurements among the specimens are the maxilla length (MXL) and the pre‐dorsal distance (PDD). Analysis of canonical variables indicates three distinct groups in the first canonical axis formed by: (1) Três Bocas Stream, (2) Rancho Alegre + Vermelho River + EPUNOPAR and (3) EPUEL + Paranapanema River. This axis retained 79·4% of information from the original matrix. Analysis of morphometrics reveals differences among populations from the Paranapanema River basin and between these and the specimen from Surinam. The morphometric and cytogenetic differences among the studied populations suggest a species complex.