bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid cell expansion and cellulose synthesis regulated by plasmodesmata and sugar: insights from the single-celled cotton fibre
Authors: Ruan Yong-Ling
Published: January 2007

Higher plants comprise mixtures of some 40 different cell types, and this often complicates the interpretation of data obtained at the tissue level. Studies for a given cell type may provide novel insights into the mechanisms underlying defined cellular and developmental processes. In this regard, the cotton fibre represents an excellent single-cell model to study the control of rapid cell elongation and cellulose synthesis. These single cells, initiated from the ovule epidermis at anthesis, typically elongate to ~3–5 cm in the tetraploid species before they switch to intensive secondary cell wall cellulose synthesis. By maturity, more than 94% of fibre weight is cellulose. To unravel the mechanisms of fibre elongation and cellulose synthesis, two hypotheses have been examined: (a) that sucrose degradation and utilisation mediated by sucrose synthase (Sus) may play roles in fibre development and (b) that symplastic isolation of the fibre cells may be required for their rapid elongation. Reverse genetic and biochemical analyses have revealed the critical role that Sus plays in fibre initiation and early elongation. Late in development, plasma-membrane and cell wall association of Sus protein seems to be involved in rapid cellulose synthesis. Cell biology and gene expression studies showed a temporary closure of fibre plasmodesmata (PD), probably due to the deposition of callose, at the rapid phase of elongation. The duration of the PD closure correlates positively with the final fibre length attained. These data support the view that PD closure may be required for fibres to achieve extended elongation. The branching of PD towards the secondary cell wall stage is postulated to function as a molecule sieve for tight control of macromolecule trafficking into fibres to sustain intensive cellulose synthesis.
Transcriptional profiling of chickpea genes differentially regulated by salicylic acid, methyl jasmonate and aminocyclopropane carboxylic acid to reveal pathways of defence-related gene regulation
Authors: Coram Tristan E. , Pang Edwin C. K.
Published: January 2007

Using microarray technology and a set of chickpea (Cicer arietinum L.) unigenes and grasspea (Lathyrus sativus L.) expressed sequence tags, chickpea responses to treatments with the defence signalling compounds salicylic acid (SA), methyl jasmonate (MeJA) and aminocyclopropane carboxylic acid (ACC) were studied in three chickpea genotypes with ranging levels of resistance to ascochyta blight [Ascochyta rabiei (Pass.) L.]. The experimental system minimised environmental effects and was conducted in reference design, where samples from untreated controls acted as references against post-treatment samples. Microarray observations were also validated by quantitative reverse transcription–polymerase chain reaction. The time-course expression patterns of 715 experimental microarray features resulted in differential expression of 425 transcripts. The A. rabiei resistant chickpea genotypes showed a more substantial range of defence-related gene induction by all treatments, indicating that they may possess stronger abilities to resist pathogens. Further, the involvement of SA, MeJA and ACC signalling was identified for the regulation of some important A. rabiei responsive transcripts, as well as cross-talk between these pathways. In the current study we also found evidence to suggest the involvement of A. rabiei-specific signalling mechanisms for the induction of several transcripts that were previously implicated in A. rabiei resistance. This study characterised the regulatory mechanisms of many chickpea transcripts that may be important in defence against various pathogens, as well as other cellular functions. These results provide novel insights to the molecular control of chickpea cellular processes, which may assist the understanding of chickpea defence mechanisms and allow enhanced development of disease resistant cultivars.
An infectious retrovirus susceptible to an IFN antiviral pathway from human prostate tumors
Authors: Dong Beihua , Kim Sanggu , Hong Seunghee , Das Gupta Jaydip , Malathi Krishnamurthy , Klein Eric A. , Ganem Don , DeRisi Joseph L. , Chow Samson A. , Silverman Robert H.
Published: January 2007

We recently reported identification of a previously undescribed gammaretrovirus genome, xenotropic murine leukemia virus-related virus (XMRV), in prostate cancer tissue from patients homozygous for a reduced activity variant of the antiviral enzyme RNase L. Here we constructed a full-length XMRV genome from prostate tissue RNA and showed that the molecular viral clone is replication-competent. XMRV replication in the prostate cancer cell line DU145 was sensitive to inhibition by IFN-β. However, LNCaP prostate cancer cells, which are deficient in JAK1 and RNase L, were resistant to the effects of IFN-β against XMRV. Furthermore, DU145 cells rendered deficient in RNase L with siRNA were partially resistant to IFN inhibition of XMRV. Expression in hamster cells of the xenotropic and polytropic retrovirus receptor 1 allowed these cells to be infected by XMRV. XMRV provirus integration sites were mapped in DNA isolated from human prostate tumor tissue to genes for two transcription factors (NFATc3 and CREB5) and to a gene encoding a suppressor of androgen receptor transactivation (APPBP2/PAT1/ARA67). Our studies demonstrate that XMRV is a virus that has infected humans and is susceptible to inhibition by IFN and its downstream effector, RNase L.
The Discovery of the J Particle; A Personal Recollection
Authors: Samuel C C Ting
Published: January 2007

Without abstract, see full text
Electron Energy Distribution in a High Pressure Gas Discharge Sustained by a High Current Electron Beam
Authors: Michail B Tendler
Published: January 2007

The electron energy distribution in a high pressure molecular gas discharge sustained by a high current electron beam is calculated for the electron energies strongly exceeding the ionization energy. The consideration is valid also for the non-uniform local distribution in velocity space. An approximate analytical solution is carried out, and the expression for the integrated distribution function F(ν)= ∫ ν
f(
ν, r
)dθd3
r is given. Using this function we calculate the number of ionizations assuming three-body recombination as the main loss mechanism. We also calculate the specific energy deposited in the gas mixture and compare it with experimental results. The agreement is found to be reasonable, which emphasizes the necessity of the kinetic approach.
Theoretical Determinations of Spin Densities
Authors: A J Freeman
Published: January 2007

This paper describes and discusses some aspects of the present status of theoretical determinations of spin (and charge) densities in atoms, molecular clusters, and solids. Selected results of recently completed calculations are used to illustrate "state of the art" methodology and accomplishments.
The Experimental Determination of Electron Momentum Densities
Authors: Brian G Williams
Published: January 2007

Recent developments and the current state of experimental methods for the determination of electron momentum densities (EMD's) are reviewed. The remarkable growth both in applications of traditional techniques as well as in the development of new techniques over the last three years is described. A general analysis of the determination of EMD's in atoms, molecules and solids provides the context within which the recent work is discussed. This leads to a consideration of the physical information contained in the EMD and hence to the experimental conditions needed to ensure that the information obtained is meaningful. The potential for improving the quality of the information obtained by separating the partial contributions to the total EMD on the basis of the electron spin, orbital energy or position is discussed. The three commonly used probes, inelastic photon or electron scattering and positron annihilation are discussed in turn. Photon scattering experiments are subdivided into X-ray and γ-ray work. These techniques are well established but experiments with new sources such as Au, which emits high energy γ-rays, and synchrotrons, which provide polarized radiation, promise to open up new areas for investigation. Refinements of the technique, such as the detection of the ejected electron in coincidence with the scattered photon, are also discussed. Inelastic scattering of high energy electrons, a refinement of which is the (e,2e) technique, has been developed mainly in the last few years but is already making major contributions to the understanding of EMD's. Using both methods excellent resolution is available and the (e,2e) technique allows one to measure all three components of the EMD while at the same time separating out contributions to the total profile on the basis of orbital energies. The potential application of this technique to solids opens up many exciting possibilities. Developments in the determination of EMD's from angular correlation measurements of two photon positron annihilation are then described. Recent work in this relatively well established field includes the development of multi-counter detecting systems for the direct determination of two components of the EMD as well as the possibility of determining all three components. Other developments such as the use of polarized positrons to determine the EMD of unpaired spin electrons are also considered. The main difficulty associated with the interpretation of positron data arises from uncertainty in the analysis of the behaviour of the positron and this remains the outstanding problem. Results for specific samples obtained over the last three years using the above techniques are then described with a view to assessing the importance of EMD work as well as to providing guidance for future work.
Interpretation of Experimental Charge Densities. The study of chemical bonding
Authors: Pierre Becker
Published: January 2007

The first question to be discussed here is what kind of diffraction theory is applicable to the sample under study. The range between kinematical and dynamical theory is so wide that the problem has to be considered very seriously. It is necessary to consider the relative influence of thermal diffuse scattering versus Bragg scattering, in order to obtain the average of the structure factors over the lattice modes. A limit of resolution results from the series termination error: the neglect of core polarisation and the necessity to define a deformation density; obtained by subtracting isolated vibrating atoms. Various sources of error are discussed, and especially the problems related to the scale factor. The experiments are concluded to be more reliable than most calculations at a distance larger than 0.3 Å from the nuclei. The analysis can be done either in real or reciprocal space. A qualitative description of the possible types of bonding has been undertaken few years ago and a systematisation is now becoming possible. The "chemical bonds" are described in different terms depending whether one looks at the total or deformation density. To go towards a quantitative description, two major problems have to be solved: the influence of thermal motion on the density or the molecular properties, and the definition of proper molecular regions in the solid. It should be kept in mind that intermolecular effects are now in the domain of observability and therefore a combination of theoretical and experimental work should become very fruitful for the study of crystalline forces. In reciprocal space, the problem is to find models that represent the structure factor. It is possible to think in terms of an orbital expansion: one has to deal with the very complicated two center form factors, and an attribution of a temperature factor to these factors is impossible. Better models are based in a functional partitioning of the density in terms of deformation functions around each nucleus. A careful study of correlation between different functions leads to a multipolar expansion. But, in order to deduce unbiased properties, the influence of internal modes of vibration has to be considered carefully. An interplay with other techniques is necessary if one wants to get precise information on the density near atomic positions.
Experimental Investigations of Bonding Charges in Diamond and Zinc Blende Structures
Authors: R Colella
Published: January 2007

A major source of information concerning bonding charges in diamond structures is provided by the weak non-zero forbidden reflections of the type: h + k + l = 4n + 2. In the early determinations of the (222) a lot of attention was devoted to perturbing effects such as "Umweganregung" and lattice defects. Neutron and X-ray diffraction measurements confirmed the electronic origin of the (222) intensity, and established the existence of anharmonic contributions at temperatures above R.T., particularly in the case of the (442) in Si. A non-zero (222) intensity was also found in grey-tin. "Pendellösung" techniques can also be applied, especially in conjunction with high intensity X-ray sources. In the case of III-V semiconducting compounds, such as InSb, reflections for which h + k + l = 4n + 2 are not completely forbidden. They are still interesting for bonding charge density studies, however. Reflections like (200), for example, when compared with the free-atom value, provide information about charge transfer and, or, interstitial charges placed off center along the bond. Reflections like (222) and (2̄2̄2̄) are found different whereas they should be rigorously equal, even considering the violation of Friedel's law owing to anomalous dispersion. Such a difference is a direct indication of asphericity of the valence electrons. A phenomenological two-parameter model based on a tetrahedral distortion of the valence charge density and a charge transfer from In to Sb provides excellent fitting with experiment. It is also found that the difference (222-2̄2̄2̄) decreases gradually with temperature, between 400 K and 16 K. We have interpreted this result by assuming that the amount of tetrahedral distortion and charge transfer vary with temperature.
Some Properties of Commutators and the Equations of Motion
Authors: A Jannussis  , A Streclas  , D Sourlas  , K Vlachos
Published: January 2007

In this paper we calculate the commutators of operator functions for non-commuting operators on a Heisenberg ring. The commutator of two operators can be expressed with the help of the fundamental operators and their differentials. Using the theorem of the derivative of a function of operators with respect to any parameter, we can find tne equation of motion of a system, in canonical and non-canonical quantum mechanics.
Energy Levels and Oscillator Strengths for 3s23pn-3s23pn-13d transitions of Fe X and Fe XI
Authors: G E Bromage  , R D Cowan  , B C Fawcett
Published: January 2007

Energy levels and oscillator strengths are calculated for the 3s23pn-3s23pn-13dtransition arrays of Fe X and Fe XI. The Slater radial integrals for these computations are adjusted so as to become consistent with established energy levels. Pertinent configuration interactions are included and the interaction integrals are reduced by up to 35% from values calculatedab initio, to achieve consistency. Predictions from this analysis lead to new line identifications in solar and laboratory spectra.
Search for Superheavy Elements in Uranium Minerals Using K X-ray Fluorescence Analysis
Authors: J Kantele
Published: January 2007

Selected uranium mineral joints having high uranium contents (40 to 80%) were irradiated with 279.2 keV γ-rays from a203Hg source, and an attempt was made to observe fluorescentKX-rays of superheavy elements. An upper limit of 1 ppm was obtained for the concentration of each of the elementsZ= 121 to 127 in uranium. It is suggested that another version of the present method be applied to a study of giant-halo inclusions in whichKX-rays of superheavy elements could more likely be observed.
On Changes of Variables in Kinetic Theory
Authors: Erling Dahlberg
Published: January 2007

It is shown that an appropriate and systematic use of a well-defined set of collision variables allows a straightforward, concise, and comprehensible presentation of typical transformation results; e.g. Boltzmann's collision term, its adaptation for electrons in a cold gas, and Enskog's symmetrickernel form for the linearized equation. It is also shown how the Allis and Allen form of the left member of Boltzmann's equation (suitable for cases with cylindrical symmetry) can be given a correct derivation and interpretation.
Prediction and Identification of Some Transitions Associated with 2pkand 2pk-13l Configurations in Six-, Seven- and Eight-electron Ions
Authors: S O Kastner  , A K Bhatia  , Leonard Cohen
Published: January 2007

Calculations of fine structure and transition probabilities, using the SUPERSTRUCTURE program developed at University College London, have been carried out for the 2pkand 2pk-13lconfigurations of ions with six, seven or eight electrons. The predicted line patterns are compared with existing observations for silicon, sulfur, argon and calcium to yield some new identifications in laboratory and solar spectra and to indicate some transitions, as yet unobserved, that may be of observational importance.
Hartree-Fock and Configuration Interaction Calculations of Hyperfine Constants in Quartet States of Three-electron Atoms
Authors: Sten Lunell  , Nelson H F Beebe
Published: January 2007

The hyperfine structure constants in the lowest4Poand4Pestates of the isoelectronic sequence Li-F6+have been calculated from Hartree-Fock and accurate configuration interaction (CI) wavefunctions, in good agreement with available experimental results for Li. In addition, Hartree-Fock calculations of energies and hfs constants for several higher4S,4Po,4Dand4Dostates of Li are reported.
The X-ray Atomic Scattering Factors of Aluminium Powder at 80 K
Authors: E Rantavuori  , V-P Tanninen
Published: January 2007

The atomic scattering factors of aluminium have been measured at 80 K using powder samples. The results confirm earlier measurements at room temperature and are in agreement with theory by Ascarelli and Raccah.
Magnetic Susceptibility Resistivity and Thermal Expansion Measurements on FeP
Authors: B Westerstrandh  , L Lundgren  , U Gäfvert  , B Carlsson
Published: January 2007

Susceptibility, resistivity and thermal expansion measurements have been performed on single crystals of FeP. The temperature ranges were 4.2 K-300 K, 15 K-300 K and 95 K-300 K respectively. The susceptibility measurements show a magnetic transition at 120 K, which is due to an antiferromagnetic ordering in the ab-plane. AboveTNthere is a considerable amount of anisotropy. The susceptibility curves representing the three principal directions have maxima around 220 K. The magnetic structure is interpreted in terms of a linear chain model. This interpretation of the experimental results is based on the theoretical work by Kallel et al. Resistivity measurements, carried out with the van der Pauw method, give an anisotropic resistivity tensor. The resistivity vs. temperature curves have points of inflexion at 115 K. The thermal expansion coefficient of the b-axis is much larger than the coefficients of the other axes.
A Complementary Study of Photospallation Systematics
Authors: G G Jonsson  , K Lindgren
Published: January 2007

Recently measured photon-induced spallation yields have been compiled and analysed with the Rudstam five-parameter CDMD formula. The mass and energy dependence as well as the absolute values of the parameters are consistent with earlier findings.
Plasma-Neutral Gas Interaction Effects on the Stability of Drift Modes
Authors: D E Ohlsson
Published: January 2007

In quasi-steady fusion reactors partially ionized boundary layers are likely to be formed. The plasma density is then expected to be peaked close to the boundary. The possibility of large density gradients driving unstable drift modes in these layers is investigated. The expected magnetic shear, due to induced plasma currents in such systems, as well as minimum-average-Bproperties of the magnetic field, are probably insufficient to significantly influence the stability properties of these modes. However, effects associated with plasma-neutral gas interactions as well as with a finite Larmor radius and ion viscosity modify the behaviour of drift modes and introduce stabilizing effects.
Ohmic Plasma Heating by Magnetic Field – Aligned Currents in an Internal Ring Configuration
Authors: D Ohlsson
Published: January 2007

This investigation concerns heating of a plasma being impermeable to neutral gas and situated in a magnetic bottle where the confining field is generated mainly by the current in a supported internal ring. The losses to the ring supports are considered in terms of a single-particle model. The reduction of these losses due to magnetic support shielding is investigated. Further, all transport processes are assumed to be of classical origin, but anomalous effects can be simulated by introducing certain numerical factors. The possibility of local concentration of the induced heating current resulting in a thermal instability is also investigated. Particular interest is focused on the relation between the heat loss to the supports and the threshold condition for this instability. The results of the present investigation have been derived from numerical solutions of a set of nonstationary macroscopic fluid equations.
Determination of g-factor Ratios for Cs+Ions and Cs Atoms
Authors: A F Oluwole
Published: January 2007

A charge-exchange optical pumping experiment to measure the nucleargfactor of133Cs+ions in a He buffer gas is reported. Cs+ions are polarized by charge-exchange collisons with optically pumped Cs atoms. The NMR frequency of133Cs+ions along with the Zeeman transition frequency of133Cs are measured in a magnetic field ∼ 600 G. This gives the ratio of the nucleargfactor of the133Cs+ion to the electronicgfactor in the ground electronic state of free133Cs. The result isgI(133Cs+)/gJ(133Cs)=-1.9917235(30). Using this value and results of other researchers yieldgI(133Cs+)/gI(133Cs)=0.9999917(21) as the ratio of the nucleargfactor of the Cs ions to that of the free Cs atoms, [σ(Cs+)-σ(Cs)]=7.7(2.0) × 10-6the difference in the diamagnetic shielding constants of the free atoms and ions. Finally, the value for the shielded Cs+nuclear moment in units of the Bohr magneton is found to begI(133Cs+)=3.988511(21) × 10-4.
Temperature and Pressure Dependence of the Band Structure in Bismuth
Authors: Brage Norin
Published: January 2007

The empirical pseudopotential theory both in the Heine-Abarenkov model (H-A) and in Shaws optimized model (OMP) is used in a systematic investigation of the temperature and the pressure dependence of the levels in the vicinity of the Fermi level of bismuth (Bi). The band ordering in the L-point and in the T-point is discussed. The differences between the results in the H-A model and in Shaws OMP model, the influence of damping factors and the consequences of taking exchange and correlation effects among the conduction electrons into account, are investigated.
On the Origin of Asymmetry of XES and XPS Core Lines of Iron Transition Metals: Experiment on Cu–Mn Alloys
Authors: V M Pessa
Published: January 2007

The author shows that the width and asymmetry of the MnKα1(1s1/2-2p3/2) X-ray emission line correlate with a magneton number of Mn atoms in copper-manganese binary alloys. This correlation seems to originate from exchange interaction between a core hole (2p) and unpaired 3delectrons in Mn. The author suggests that 2p-3dinteraction is probably a more significant effect than many-body final state effects in shaping theKα X-ray emission and 2pphotoemission lines for pure iron transition metals and their alloys.
Simulating multiplexed SNP discovery rates using base-specific cleavage and mass spectrometry
Authors: Böcker Sebastian
Published: January 2007

Motivation: Single Nucleotide Polymorphisms (SNPs) are believed to contribute strongly to the genetic variability in living beings, and SNP and mutation discovery are of great interest in today's Life Sciences. A comparatively new method to discover such polymorphisms is based on base-specific cleavage, where resulting cleavage products are analyzed by mass spectrometry (MS). One particular advantage of this method is the possibility of multiplexing the biochemical reactions, i.e. examining multiple genomic regions in parallel. Simulations can help estimating the performance of a method for polymorphism discovery, and allow us to evaluate the influence of method parameters on the discovery rate, and also to investigate whether the method is well suited for a certain genomic region.

Results: We show how to efficiently conduct such simulations for polymorphism discovery using base-specific cleavage and MS. Simulating multiplexed polymorphism discovery leads us to the problem of uniformly drawing a multiplex. Given a multiset of natural numbers we want to uniformly draw a subset of fixed cardinality so that the elements sum up to some fixed total length. We show how to enumerate multiplex layouts using dynamic programming, which allows us to uniformly draw a multiplex.

Contact:  boecker@minet.uni-jena.de
A novel pattern recognition algorithm to classify membrane protein unfolding pathways with high-throughput single-molecule force spectroscopy
Authors: Marsico Annalisa , Labudde Dirk , Sapra Tanuj , Muller Daniel J. , Schroeder Michael
Published: January 2007

Motivation: Misfolding of membrane proteins plays an important role in many human diseases such as retinitis pigmentosa, hereditary deafness and diabetes insipidus. Little is known about membrane proteins as there are only very few high-resolution structures. Single-molecule force spectroscopy is a novel technique, which measures the force necessary to pull a protein out of a membrane. Such force curves contain valuable information on the protein structure, conformation, and inter- and intra-molecular forces. High-throughput force spectroscopy experiments generate hundreds of force curves including spurious ones and good curves, which correspond to different unfolding pathways. Manual analysis of these data is a bottleneck and source of inconsistent and subjective annotation.

Results: We propose a novel algorithm for the identification of spurious curves and curves representing different unfolding pathways. Our algorithm proceeds in three stages: first, we reduce noise in the curves by applying dimension reduction; second, we align the curves with dynamic programming and compute pairwise distances and third, we cluster the curves based on these distances. We apply our method to a hand-curated dataset of 135 force curves of bacteriorhodopsin mutant P50A. Our algorithm achieves a success rate of 81% distinguishing spurious from good curves and a success rate of 76% classifying unfolding pathways. As a result, we discuss five different unfolding pathways of bacteriorhodopsin including three main unfolding events and several minor ones. Finally, we link folding barriers to the degree of conservation of residues. Overall, the algorithm tackles the force spectroscopy bottleneck and leads to more consistent and reproducible results paving the way for high-throughput analysis of structural features of membrane proteins.

Contact:  annalisa.marsico@biotec.tu-dresden.de
EBIMed—text crunching to gather facts for proteins from Medline
Authors: Rebholz-Schuhmann Dietrich , Kirsch Harald , Arregui Miguel , Gaudan Sylvain , Riethoven Mark , Stoehr Peter
Published: January 2007

Summary: To allow efficient and systematic retrieval of statements from Medline we have developed EBIMed, a service that combines document retrieval with co-occurrence-based analysis of Medline abstracts. Upon keyword query, EBIMed retrieves the abstracts from EMBL-EBI's installation of Medline and filters for sentences that contain biomedical terminology maintained in public bioinformatics resources. The extracted sentences and terminology are used to generate an overview table on proteins, Gene Ontology (GO) annotations, drugs and species used in the same biological context. All terms in retrieved abstracts and extracted sentences are linked to their entries in biomedical databases. We assessed the quality of the identification of terms and relations in the retrieved sentences. More than 90% of the protein names found indeed represented a protein. According to the analysis of four protein–protein pairs from the Wnt pathway we estimated that 37% of the statements containing such a pair mentioned a meaningful interaction and clarified the interaction of Dkk with LRP. We conclude that EBIMed improves access to information where proteins and drugs are involved in the same biological process, e.g. statements with GO annotations of proteins, protein–protein interactions and effects of drugs on proteins.

Availability: Available at

Supplementary Data: Supplementary Data are available at Bioinformatics online.

Contact:  Rebholz@ebi.ac.uk
ISIS: interaction sites identified from sequence
Authors: Ofran Yanay , Rost Burkhard
Published: January 2007

Motivation: Large-scale experiments reveal pairs of interacting proteins but leave the residues involved in the interactions unknown. These interface residues are essential for understanding the mechanism of interaction and are often desired drug targets. Reliable identification of residues that reside in protein–protein interface typically requires analysis of protein structure. Therefore, for the vast majority of proteins, for which there is no high-resolution structure, there is no effective way of identifying interface residues.

Results: Here we present a machine learning-based method that identifies interacting residues from sequence alone. Although the method is developed using transient protein–protein interfaces from complexes of experimentally known 3D structures, it never explicitly uses 3D information. Instead, we combine predicted structural features with evolutionary information. The strongest predictions of the method reached over 90% accuracy in a cross-validation experiment. Our results suggest that despite the significant diversity in the nature of protein–protein interactions, they all share common basic principles and that these principles are identifiable from sequence alone.

Contact:  yanay.ofran@columbia.edu
Phylogeny reconstruction: increasing the accuracy of pairwise distance estimation using Bayesian inference of evolutionary rates
Authors: Ninio Matan , Privman Eyal , Pupko Tal , Friedman Nir
Published: January 2007

Distance-based methods for phylogeny reconstruction are the fastest and easiest to use, and their popularity is accordingly high. They are also the only known methods that can cope with huge datasets of thousands of sequences. These methods rely on evolutionary distance estimation and are sensitive to errors in such estimations. In this study, a novel Bayesian method for estimation of evolutionary distances is developed. The proposed method enables the use of a sophisticated evolutionary model that better accounts for among-site rate variation (ASRV), thereby improving the accuracy of distance estimation. Rate variations are estimated within a Bayesian framework by extracting information from the entire dataset of sequences, unlike standard methods that can only use one pair of sequences at a time. We compare the accuracy of a cascade of distance estimation methods, starting from commonly used methods and moving towards the more sophisticated novel method. Simulation studies show significant improvements in the accuracy of distance estimation by the novel method over the commonly used ones. We demonstrate the effect of the improved accuracy on tree reconstruction using both real and simulated protein sequence alignments. An implementation of this method is available as part of the SEMPHY package.

Contact:  talp@tau.ac.il
Simultaneous alignment and annotation ofcis-regulatory regions
Authors: Bais Abha Singh , Grossmann Steffen , Vingron Martin
Published: January 2007

Motivation: Current methods that annotate conserved transcription factor binding sites in an alignment of two regulatory regions perform the alignment and annotation step separately and combine the results in the end. If the site descriptions are weak or the sequence similarity is low, the local gap structure of the alignment poses a problem in detecting the conserved sites. It is therefore desirable to have an approach that is able to simultaneously consider the alignment as well as possibly matching site locations.

Results: With SimAnn we have developed a tool that serves exactly this purpose. By combining the annotation step and the alignment of the two sequences into one algorithm, it detects conserved sites more clearly. It has the additional advantage that all parameters are calculated based on statistical considerations. This allows for its successful application with any binding site model of interest. We present the algorithm and the approach for parameter selection and compare its performance with that of other, non-simultaneous methods on both simulated and real data.

Availability: A command-line based C++ implementation of SimAnn is available from the authors upon request. In addition, we provide Perl scripts for calculating the input parameters based on statistical considerations.

Contact:  bais@molgen.mpg.de
Phylogenetic reconstruction from non-genomic data
Authors: Clemente José C. , Satou Kenji , Valiente Gabriel
Published: January 2007

Motivation: Recent results related to horizontal gene transfer suggest that phylogenetic reconstruction cannot be determined conclusively from sequence data, resulting in a shift from approaches based on polymorphism information in DNA or protein sequence to studies aimed at understanding the evolution of complete biological processes. The increasing amount of available information on metabolic pathways for several species makes it of greater relevance to understand the similarities and differences among such pathways. These similarities can then be used to infer phylogenetic trees not based exclusively in sequence data, therefore avoiding the previously mentioned problems.

Results: In this article, we present a method to assess the structural similarity of metabolic pathways for several organisms. Our algorithms work by using one of the three possible enzyme similarity measures (hierarchical, information content, gene ontology), and one of the two clustering methods (neighbor-joining, unweighted pair group method with arithmetic mean), to produce a phylogenetic tree both in Newick and graphic format. The web server implementing our algorithms is optimized to answer queries in linear time.

Availability: The software is available for free public use on a web server, at the address . It is available on demand in source code form for research use to educational institutions, non-profit research institutes, government research laboratories and individuals, for non-exclusive use, without the right of the licensee to further redistribute the source code.

Contact:  valiente@lsi.upc.edu; clemente@jaist.ac.jp
Using an alignment of fragment strings for comparing protein structures
Authors: Friedberg Iddo , Harder Tim , Kolodny Rachel , Sitbon Einat , Li Zhanwen , Godzik Adam
Published: January 2007

Motivation: Most methods that are used to compare protein structures use three-dimensional (3D) structural information. At the same time, it has been shown that a 1D string representation of local protein structure retains a degree of structural information. This type of representation can be a powerful tool for protein structure comparison and classification, given the arsenal of sequence comparison tools developed by computational biology. However, in order to do so, there is a need to first understand how much information is contained in various possible 1D representations of protein structure.

Results: Here we describe the use of a particular structure fragment library, denoted here as KL-strings, for the 1D representation of protein structure. Using KL-strings, we develop an infrastructure for comparing protein structures with a 1D representation. This study focuses on the added value gained from such a description. We show the new local structure language adds resolution to the traditional three-state (helix, strand and coil) secondary structure description, and provides a high degree of accuracy in recognizing structural similarities when used with a pairwise alignment benchmark. The results of this study have immediate applications towards fast structure recognition, and for fold prediction and classification.

Contact:  idoerg@burnham.org

Supplementary information:  ECCB06-supplement
Multiple alignment by sequence annealing
Authors: S. Schwartz Ariel , Pachter Lior
Published: January 2007

Motivation: We introduce a novel approach to multiple alignment that is based on an algorithm for rapidly checking whether single matches are consistent with a partial multiple alignment. This leads to a sequence annealing algorithm, which is an incremental method for building multiple sequence alignments one match at a time. Our approach improves significantly on the standard progressive alignment approach to multiple alignment.

Results: The sequence annealing algorithm performs well on benchmark test sets of protein sequences. It is not only sensitive, but also specific, drastically reducing the number of incorrectly aligned residues in comparison to other programs. The method allows for adjustment of the sensitivity/specificity tradeoff and can be used to reliably identify homologous regions among protein sequences.

Availability: An implementation of the sequence annealing algorithm is available at

Contact: sariel@cs.berkeley.edu
Electrostatic potentials of proteins in water: a structured continuum approach
Authors: Hildebrandt Andreas , Blossey Ralf , Rjasanow Sergej , Kohlbacher Oliver , Lenhof Hans-Peter
Published: January 2007

Electrostatic interactions play a crucial role in many biomolecular processes, including molecular recognition and binding. Biomolecular electrostatics is modulated to a large extent by the water surrounding the molecules. Here, we present a novel approach to the computation of electrostatic potentials which allows the inclusion of water structure into the classical theory of continuum electrostatics. Based on our recent purely differential formulation of nonlocal electrostatics [Hildebrandt, et al. (2004)Phys. Rev. Lett., 93, 108104] we have developed a new algorithm for its efficient numerical solution. The key component of this algorithm is a boundary element solver, having the same computational complexity as established boundary element methods for local continuum electrostatics. This allows, for the first time, the computation of electrostatic potentials and interactions of large biomolecular systems immersed in water including effects of the solvent's structure in a continuum description. We illustrate the applicability of our approach with two examples, the enzymes trypsin and acetylcholinesterase. The approach is applicable to all problems requiring precise prediction of electrostatic interactions in water, such as protein–ligand and protein–protein docking, folding and chromatin regulation. Initial results indicate that this approach may shed new light on biomolecular electrostatics and on aspects of molecular recognition that classical local electrostatics cannot reveal.

Contact:  anhi@bioinf.uni-sb.de
Optimization of probe coverage for high-resolution oligonucleotide aCGH
Authors: Lipson Doron , Yakhini Zohar , Aumann Yonatan
Published: January 2007

Motivation: The resolution at which genomic alterations can be mapped by means of oligonucleotide aCGH (array-based comparative genomic hybridization) is limited by two factors: the availability of high-quality probes for the target genomic sequence and the array real-estate. Optimization of the probe selection process is required for arrays that are designed to probe specific genomic regions in very high resolution without compromising probe quality constraints.

Results: In this paper we describe a well-defined optimization problem associated with the problem of probe selection for high-resolution aCGH arrays. We propose the whenever possible ∈-cover as a formulation that faithfully captures the requirement of probe selection problem, and provide a fast randomized algorithm that solves the optimization problem in O(n logn) time, as well as a deterministic algorithm with the same asymptotic performance. We apply the method in a typical high-definition array design scenario and demonstrate its superiority with respect to alternative approaches.

Availability: Address requests to the authors.

Contact:  dlipson@cs.technion.ac.il
Genetic code symmetry and efficient design of GC-constrained coding sequences
Authors: Gavish Matan , Peled Amnon , Chor Benny
Published: January 2007

Motivation: Cloning of long DNA sequences (40–60 bases) into phage display libraries using polymerase chain reaction (PCR) is a low efficiency process, in which PCR is used to incorporate a DNA insert, coding for a certain peptide, into the amplified sequence. The PCR efficiency in this process is strongly affected by the distribution of G–C bases in the amplified sequence. As any DNA insert coding for the target peptide may be attempted, there is a flexibility in choosing part of the amplified sequence. Since the number of inserts coding for the same peptide is exponential in the peptide length, a computational problem naturally arises—that of efficiently finding an insert, whose parameters are optimal for PCR cloning.

Results: The GC distribution requirements are formulated as a search problem. We developed an efficient, linear time ‘one pass’ algorithm for this problem. Interestingly, our algorithm strongly relies on an interesting symmetry, which we observed in the standard genetic code. Most non-standard genetic codes examined possess this symmetry as well, yet some do not. We generalize the search problem and consider the case of a non-standard, or arbitrary, genetic code where this symmetry does not necessary hold. We solve the generalized problem in polynomial, but nonlinear, time.

Availability: An implementation of the proposed algorithm is available upon request from the authors.

Contact:  benny@cs.tau.ac.il
A tale of two tails: why are terminal residues of proteins exposed?
Authors: Jacob Etai , Unger Ron
Published: January 2007

Motivation: It is widely known that terminal residues of proteins (i.e. the N- and C-termini) are predominantly located on the surface of proteins and exposed to the solvent. However, there is no good explanation as to the forces driving this phenomenon. The common explanation that terminal residues are charged, and charged residues prefer to be on the surface, cannot explain the magnitude of the phenomenon. Here, we survey a large number of proteins from the PDB in order to explore, quantitatively, this phenomenon, and then we use a lattice model to study the mechanisms involved.

Results: The location of the termini was examined for 425 small monomeric proteins (50–200 amino acids) and it was found that the average solvent accessibility of termini residues is 87.1% compared with 49.2% of charged residues and 35.9% of all residues. Using a cutoff of 50% of the maximal possible exposure, 80.3% of the N-terminal and 86.1% of the C-terminal residues are exposed compared to 32% for all residues. In addition, terminal residues are much more distant from the center of mass of their proteins than other residues. Using a 2D lattice, a large population of model proteins was studied on three levels: structural selection of compact structures, thermodynamic selection of conformations with a pronounced energy gap and kinetic selection of fast folding proteins using Monte-Carlo simulations. Progressively, each selection raises the proportion of proteins with termini on the surface, resulting in similar proportions to those observed for real proteins.

Contact:  ron@biocom1.ls.biu.ac.il
Learning probabilistic models ofcis-regulatory modules that represent logical and spatial aspects
Authors: Noto Keith , Craven Mark
Published: January 2007

Motivation: The process of transcription is controlled by systems of factors which bind in specific arrangements, called cis-regulatory modules (CRMs), in promoter regions. We present a discriminative learning algorithm which simultaneously learns the DNA binding site motifs as well as the logical structure and spatial aspects of CRMs.

Results: Our results on yeast datasets show better predictive accuracy than a current state-of-the-art approach on the same datasets. Our results on yeast, fly and human datasets show that the inclusion of logical and spatial aspects improves the predictive accuracy of our learned models.

Availability: Source code is available at

Contact:  noto@cs.wisc.edu
Designing patterns for profile HMM search
Authors: Sun Yanni , Buhler Jeremy
Published: January 2007

Motivation: Profile HMMs are a powerful tool for modeling conserved motifs in proteins. These models are widely used by search tools to classify new protein sequences into families based on domain architecture. However, the proliferation of known motifs and new proteomic sequence data poses a computational challenge for search, requiring days of CPU time to annotate an organism's proteome.

Results: We use PROSITE-like patterns as a filter to speed up the comparison between protein sequence and profile HMM. A set of patterns is designed starting from the HMM, and only sequences matching one of these patterns are compared to the HMM by full dynamic programming. We give an algorithm to design patterns with maximal sensitivity subject to a bound on the false positive rate. Experiments show that our patterns typically retain at least 90% of the sensitivity of the source HMM while accelerating search by an order of magnitude.

Availability: Contact the first author at the address below.

Contact:  yanni@cse.wustl.edu
Identifying HLA supertypes by learning distance functions
Authors: Hertz Tomer , Yanover Chen
Published: January 2007

Motivation: The development of epitope-based vaccines crucially relies on the ability to classify Human Leukocyte Antigen (HLA) molecules into sets that have similar peptide binding specificities, termed supertypes. In their seminal work, Sette and Sidney defined nine HLA class I supertypes and claimed that these provide an almost perfect coverage of the entire repertoire of HLA class I molecules.

HLA alleles are highly polymorphic and polygenic and therefore experimentally classifying each of these molecules to supertypes is at present an impossible task. Recently, a number of computational methods have been proposed for this task. These methods are based on defining protein similarity measures, derived from analysis of binding peptides or from analysis of the proteins themselves.

Results: In this paper we define both peptide derived and protein derived similarity measures, which are based on learning distance functions. The peptide derived measure is defined using a peptide–peptide distance function, which is learned using information about known binding and non-binding peptides. The protein derived similarity measure is defined using a protein–protein distance function, which is learned using information about alleles previously classified to supertypes by Sette and Sidney (1999). We compare the classification obtained by these two complimentary methods to previously suggested classification methods. In general, our results are in excellent agreement with the classifications suggested by Sette and Sidney (1999) and with those reported by Buus et al. (2004).

The main important advantage of our proposed distance-based approach is that it makes use of two different and important immunological sources of information—HLA alleles and peptides that are known to bind or not bind to these alleles. Since each of our distance measures is trained using a different source of information, their combination can provide a more confident classification of alleles to supertypes.

Contact:  tomboy@cs.huji.ac.il; cheny@cs.huji.ac.il