bluuebunny/crossref_metadata_2025 huggingface dataset:
Ideal Gas Thermodynamic Properties of Sulphur Heterocyclic Compounds
Authors: Dorofeeva O. V. , Gurvich L. V.
Published: June 2010

The available structural parameters, fundamental frequencies and enthalpies of formation for thiirane, thiirene, thietane, 2H-thiete, 1,2-dithiete, tetrahydrothiophene, 2,3-dihydrothiophene, 2,5-dihydrothiophene, thiophene, 1,2-dithiolane, 1,3-dithiolane, 1,2.4-trithiolane, tetrahydro-2H-thiopyran, 5,6-dihydro-2H-thiopyran, 1,3-dithiane, 1,4-dithiane, 1,4-dithiin, 1,3,5-trithiane, thiepane and 1,3,5,7-tetrathiocane were critically evaluated and recommended values were selected. Molecular constants and enthalpies of formation for some of the molecules were estimated, as experimental values for these compounds are not available. Using the rigid-rotor harmonic-oscillator approximation, this information was used to calculate the chemical thermodynamic functions, Cp○, S°, −(G°−H0○)/T, H°−H0○, and the properties of formation, Δf H°, Δf G°, log Kf○, to 1500 K in the ideal gas state at a pressure of 1 bar. The contributions to the thermodynamic properties of compounds having inversion motion (thietane, 2,3- and 2,5-dihydrothiophene) or pseudo-rotation (tetrahydrothiophene) have been computed by employing a partition function formed by the summation of the inversional or pseudo-rotational energy levels. These energy levels have been calculated by solving the wave equation using appropriate potential functions. The calculated values of the thermodynamic functions are compared with those reported in other works. Comparison with experimental data, where such are available, is also presented. The thermodynamic properties for twelve of the compounds are reported for the first time.
Standard Reference Data for the Thermal Conductivity of Water
Authors: Ramires Maria L. V. , Nieto de Castro Carlos A. , Nagasaka Yuchi , Nagashima Akira , Assael Marc J. , Wakeham William A.
Published: June 2010

New experimental data on the thermal conductivity of liquid water along the saturation line have been obtained recently, using the bare and coated transient hot wire technique, with high accuracy. The quality of the data is such that new standard reference values can be proposed with confidence limits of 0.7% at a 95% confidence level. These data and the correlation herein presented revise a previous correlation endorsed by IUPAC.
Rate Constants for the Decay and Reactions of the Lowest Electronically Excited Singlet State of Molecular Oxygen in Solution. An Expanded and Revised Compilation
Authors: Wilkinson Francis , Helman W. Phillip , Ross Alberta B.
Published: June 2010

An expanded and revised compilation on the reactivity of singlet oxygen, the lowest electronically excited singlet state of molecular oxygen, 1O2*(1Δg), in fluid solution is presented, which supersedes the publication of Wilkinson and Brummer, J. Phys. Chem. Ref. Data 10, 809 (1981). Rate constants for the chemical reaction and physical deactivation of singlet oxygen available through 1993 have been critically compiled. Solvent deactivation rates (kd) are tabulated for 145 solvents or solvent mixtures and second-order rate constants for interaction of singlet oxygen with 1915 compounds are reported.
Atomic Weights of the Elements 1993
Authors:   IUPAC Commission on Atomic Weights and Isotopic Abundances
Published: June 2010

The biennial review of atomic weight, Ar(E), determinations and other cognate data has resulted in changes for the standard atomic weight of titanium from 47.88±0.03 to 47.867±0.001, of iron from 55.847±0.003 to 55.845±0.002, of antimony from 121.757±0.003 to 121.760±0.001, and of iridium from 192.22±0.03 to 192.217±0.003. Recent investigations on chlorine and bromine confirmed the presently accepted values of Ar(Cl) and Ar(Br). To emphasize the fact that the atomic weight of lithium commonly available in laboratory reagents can vary significantly, the value of lithium, Ar(Li), was enclosed in brackets and a footnote was added. As a result of several changes, the Table of Standard Atomic Weights Abridged to Five Significant Figures has been updated. Because relative isotope-ratio data for stable hydrogen, carbon, and oxygen are commonly being expressed on non-corresponding scales, the Commission recommends that such isotopic data be expressed only relative to the references VSMOW and VPDB. Because many elements have a different isotopic composition in some non-terrestrial materials, recent data on non-terrestrial materials are included in this report for the information of the interested scientific community.
Spectral Data for Highly Ionized Krypton, Kr V through Kr X
X
X
V
I
Authors: Shirai Toshizo , Okazaki Kiyohiko , Sugar Jack
Published: June 2010

Wavelengths, energy levels, ionization energies, line classifications, intensities and transition probabilities for Kr V through Kr XXXVI, ;with the exception of Kr XI through Kr XVII, are tabulated. No data have been published for Kr XI through Kr XVII. These data are based on the energy levels compilation of Sugar and Musgrove [13]. Transition probabilities for selected M1 lines have been reported and are quoted here. A short review of the line identifications and wavelength measurements is given for each stage of ionization. The literature has been surveyed through February 1995.
Thermodynamics of Enzyme-Catalyzed Reactions: Part 4. Lyases
Authors: Goldberg Robert N. , Tewari Yadu B.
Published: June 2010

Equilibrium constants and enthalpy changes for reactions catalyzed by the lyase class of enzymes have been compiled. For each reaction the following information is given: the reference for the data; the reaction studied; the name of the enzyme used and its Enzyme Commission number; the method of measurement; the conditions of measurement (temperature, pH, ionic strength, and the buffer(s) and cofactor(s) used); the data and an evaluation of it; and, sometimes, commentary on the data and on any corrections which have been applied to it or any calculations for which the data have been used. The data from 106 references have been examined and evaluated. Chemical Abstract Service registry numbers are given for the substances involved in these various reactions. There is a cross reference between the substances and the Enzyme Commission numbers of the enzymes used to catalyze the reactions in which the substances participate.
The Millimeter- and Submillimeter-Wave Spectrum of trans-Ethyl Alcohol
Authors: Pearson J. C. , Sastry K. V. L. N. , Winnewisser M. , Herbst Eric , De Lucia Frank C.
Published: June 2010

The rotational-torsional spectrum of the trans rotational isomer of ethyl alcohol was investigated in the 65–350 GHz frequency region. A total of 481 ground state transitions over a range of J and Ka values up to 33 and 10, respectively, were measured and assigned. Doublets or triplets arising from the A and E torsional states of the v=0 torsional level of the three-fold-symmetric methyl internal rotation have been resolved in 168 of these transitions. Internal rotation theory predicts a significant number of c-type E-state transitions normally forbidden, but allowed when the rotational asymmetry operators mix E-state rotational-torsional levels. Over 40 of these transitions have been observed. The newly measured transitions, along with the results of many previous measurements, have been analyzed using an IAM internal rotation Hamiltonian and a Watson A-reduced Hamiltonian to determine the rotational, centrifugal distortion, and torsional constants. The IAM analysis accounts for all of the analyzed transitions in the trans isomer, but for some applications the asymmetric rotor analysis is a satisfactory description of the molecule. The J and Ka limits where the trans isomer can be analyzed without considering interactions with the gauche states are also discussed. Predicted frequencies for transitions unaffected by the gauche states are presented through 600 GHz using the constants determined by this work.
Theoretical Form Factor, Attenuation, and Scattering Tabulation for Z=1–92 from E=1–10 eV to E=0.4–1.0 MeV
Authors: Chantler C. T.
Published: June 2010

Tables for form factors and anomalous dispersion are widely used in the UV, x-ray, and y-ray communities, and have existed for a considerable period of time. Much of the recent theoretical basis for these was contributed by Cromer, Mann, and Liberman while much of the experimental data were synthesized by Henke et al. More recent developments in both areas have led to new and revised tables. These works have employed numerous simplifications compared to detailed relativistic S-matrix calculations; the latter do not lend themselves to convenient tabular application for the range of Z and energy of general interest. Conversely, the former tables appear to have large regions of limited validity throughout the range of Z and energies, and in particular have important limitations with regard to extrapolation to energies outside tabulated ranges. In the present study, the primary interactions of x-rays with isolated atoms from Z=1 (hydrogen) to Z=92 (uranium) are described and computed within a self-consistent Dirac–Hartree–Fock framework. This has general application across the range of energy from 1–10 eV to 400–1000 keV, with limitations (described below) as the low- and high-energy extremes are approached.

Tabulations are provided for the f1 and f2 components of the form factors, together with the photoelectric attenuation coefficient for the atom, μ, and the value for the K-shell, μK, as functions of energy and wavelength. Also provided are estimated correction factors as described in the text, conversion factors, and a simple estimate for the sum of the scattering contributions (from an isolated atom). The method used herein is primarily theoretical and considers intermediate assumptions which limit the precision and applicability of previous theoretical tabulations. Particular concern involves the application of the dispersion relation to derive Re(f) from photoelectric absorption cross-sections. The revised formulation presented here explicitly avoids most of the limitations of previous works. Revised formulae can lead to significant qualitative and quantitative improvement, particularly above 30–60 keV energies, near absorption edges, and at 0.03 keV to 3 keV energies. Recent experimental syntheses are often complementary to this approach. Examples are given where the revised theoretical tables are in better agreement with experiment than are those based on experimental syntheses.
Summary of the Apparent Standard Partial Molal Gibbs Free Energies of Formation of Aqueous Species, Minerals, and Gases at Pressures 1 to 5000 Bars and Temperatures 25 to 1000 °C
Authors: Oelkers Eric H. , Helgeson Harold C. , Shock Everett L. , Sverjensky Dimitri A. , Johnson James W. , Pokrovskii Vitalli A.
Published: June 2010

Accurate values of the apparent standard partial molal Gibbs free energies of formation (ΔḠ°) of aqueous species, minerals, and gases at high temperatures and pressures are a requisite for characterizing a variety of industrial and natural processes including corrosion of metals, solvent extraction, crystal growth, metamorphism, and the formation of hydrothermal ore deposits. Revision of the HKF equations of state for aqueous species other than H2O (Helgeson, Kirkham and Flowers, 1981) by Tanger and Helgeson (1988) and Shock et al. (1992) permits calculation of ΔḠ° for these species at temperatures to 1000 °C and pressures to 5000 bars. The revised equations of state were combined with parameters generated by Shock and Helgeson (1988, 1990), Shock and McKinnon (1993), Shock and Koretsky (1993), Schulte and Shock (1993), Pokrovskii and Helgeson (1995 a, b, and c), and Sverjensky et al. (1995) together with densities and electrostatic properties of H2O computed from equations summarized by Johnson and Norton (1991) to calculate values of ΔḠ° for aqueous species as a function of temperature and pressure. The results of these calculations are tabulated for 348 such species, including both inorganic and organic aqueous ions, neutral species, and metal ligand complexes. Similar calculations using equations, parameters, and thermodynamic data taken from Kelley (1960), Helgeson et al. (1982), Hill (1990), Shock (1993), and Pokrovskii and Helgeson (1995 a and b) were used to generate tables of ΔḠ° for H2O, 22 minerals, and 18 gases. The tabulated values of ΔḠ°, which were generated with the aid of SUPCRT92 (Johnson et al., 1992), facilitate considerably assessment of the thermodynamic behavior of chemical processes at both high and low temperatures and pressures.
Visualizing high error levels during gene expression in living bacterial cells
Authors: Meyerovich Mor , Mamou Gideon , Ben-Yehuda Sigal
Published: June 2010

To monitor inaccuracy in gene expression in living cells, we designed an experimental system in the bacterium
Bacillus subtilis
whereby spontaneous errors can be visualized and quantified at a single-cell level. Our strategy was to introduce mutations into a chromosomally encoded
gfp
allele, such that errors in protein production are reported in real time by the formation of fluorescent GFP molecules. The data reveal that the amount of errors can greatly exceed previous estimates, and that the error rate increases dramatically at lower temperatures and during stationary phase. Furthermore, we demonstrate that when facing an antibiotic threat, an increase in error level is sufficient to allow survival of bacteria carrying a mutated antibiotic-resistance gene. We propose that bacterial gene expression is error prone, frequently yielding protein molecules that differ slightly from the sequence specified by their DNA, thus generating a cellular reservoir of nonidentical protein molecules. This variation may be a key factor in increasing bacterial fitness, expanding the capability of an isogenic population to face environmental challenges.
Use of allostery to identify inhibitors of calmodulin-induced activation of
Bacillus anthracis
edema factor
Authors: Laine Elodie , Goncalves Christophe , Karst Johanna C. , Lesnard Aurélien , Rault Sylvain , Tang Wei-Jen , Malliavin Thérèse E. , Ladant Daniel , Blondel Arnaud
Published: June 2010

Allostery plays a key role in the regulation of the activity and function of many biomolecules. And although many ligands act through allostery, no systematic use is made of it in drug design strategies. Here we describe a procedure for identifying the regions of a protein that can be used to control its activity through allostery. This procedure is based on the construction of a plausible conformational path, which describes protein transition between known active and inactive conformations. The path is calculated by using a framework approach that steers and markedly improves the conjugate peak refinement method. The evolution of conformations along this path was used to identify a putative allosteric site that could regulate activation of
Bacillus anthracis
adenylyl cyclase toxin (EF) by calmodulin. Conformations of the allosteric site at different steps along the path from the inactive (free) to the active (bound to calmodulin) forms of EF were used to perform virtual screenings and propose candidate EF inhibitors. Several candidates then proved to inhibit calmodulin-induced activation in an in vitro assay. The most potent compound fully inhibited EF at a concentration of 10 μM. The compounds also inhibited the related adenylyl cyclase toxin from
Bordetella pertussis
(CyaA). The specific homology between the putative allosteric sites in both toxins supports that these pockets are the actual binding sites of the selected inhibitors.
Contact-induced language change in a trilingual context
Authors: Munshi Sadaf
Published: June 2010

This study provides a description and analysis of contact-induced language change in a dialect of Burushaski spoken in Srinagar (India). I present a unique situation in which contact outcomes are reflected via interplay of various sociolinguistic factors involving simultaneous contact with two languages — Kashmiri and Urdu, each affecting the language in a specific way: lexical borrowing from Urdu and structural borrowing from Kashmiri. The effects of contact are examined in a trilingual context where the contact languages are placed in a dominance relationship with Urdu occupying the top of the language hierarchy while Burushaski and Kashmiri are competing at the bottom. Data indicate that lexical borrowing and structural borrowing are two different types of contact phenomena which can occur independently of each other. The two processes are influenced by different sociolinguistic factors which may interact in different ways in different contact situations resulting in different types of contact outcomes.
Motivating the emergence of new markers of sentential negation
Authors: Willis David
Published: June 2010

This article investigates the historical emergence of postverbal negation in Welsh. Welsh undergoes a shift from preverbal negation (Middle Welsh ny(t)) to postverbal negation (Present-day Welsh ddim “not” < Middle Welsh dim “at all” < dim “thing, anything”) (Jespersen’s Cycle). In Middle Welsh, ddim occupies a late clausal position, but it later undergoes a syntactic reanalysis which moves it to an earlier immediately post-subject position. It also shifts in status from a weak negative polarity item, appearing in interrogative, conditional and negative clauses, to a purely negative particle. The article argues that, when ddim begins to occupy an earlier clausal position around 1600, it becomes phonologically less salient, and subsequently loses its emphatic sense in the seventeenth and eighteenth centuries. Finally, the article considers the loss of the preverbal negative marker ni(d) in spoken Welsh, and whether this can best be understood as a push chain (ddim makes ni(d) unnecessary) or as a pull chain (ni(d) is phonologically weak and needs reinforcing by ddim). It concludes that push-chain explanations are most probable for the earlier part of the development up to 1750, with pull-chain explanations being more convincing thereafter.
The Justy mutation identifies Gon4-like as a gene that is essential for B lymphopoiesis
Authors: Lu Ping , Hankel Isaiah L. , Knisz Judit , Marquardt Andreas , Chiang Ming-Yi , Grosse Johannes , Constien Rainer , Meyer Thomas , Schroeder Andreas , Zeitlmann Lutz , Al-Alem Umaima , Friedman Ann D. , Elliott Eric I. , Meyerholz David K. , Waldschmidt Thomas J. , Rothman Paul B. , Colgan John D.
Published: June 2010

A recessive mutation named Justy was found that abolishes B lymphopoiesis but does not impair other major aspects of hematopoiesis. Transplantation experiments showed that homozygosity for Justy prevented hematopoietic progenitors from generating B cells but did not affect the ability of bone marrow stroma to support B lymphopoiesis. In bone marrow from mutant mice, common lymphoid progenitors and pre-pro–B cells appeared normal, but cells at subsequent stages of B lymphopoiesis were dramatically reduced in number. Under culture conditions that promoted B lymphopoiesis, mutant pre-pro–B cells remained alive and began expressing the B cell marker CD19 but failed to proliferate. In contrast, these cells were able to generate myeloid or T/NK precursors. Genetic and molecular analysis demonstrated that Justy is a point mutation within the Gon4-like (Gon4l) gene, which encodes a protein with homology to transcriptional regulators. This mutation was found to disrupt Gon4l pre-mRNA splicing and dramatically reduce expression of wild-type Gon4l RNA and protein. Consistent with a role for Gon4l in transcriptional regulation, the levels of RNA encoding C/EBPα and PU.1 were abnormally high in mutant B cell progenitors. Our findings indicate that the Gon4l protein is required for B lymphopoiesis and may function to regulate gene expression during this process.
Using semantic web rules to reason on an ontology of pseudogenes
Authors: Holford Matthew E. , Khurana Ekta , Cheung Kei-Hoi , Gerstein Mark
Published: June 2010

Motivation: Recent years have seen the development of a wide range of biomedical ontologies. Notable among these is Sequence Ontology (SO) which offers a rich hierarchy of terms and relationships that can be used to annotate genomic data. Well-designed formal ontologies allow data to be reasoned upon in a consistent and logically sound way and can lead to the discovery of new relationships. The Semantic Web Rules Language (SWRL) augments the capabilities of a reasoner by allowing the creation of conditional rules. To date, however, formal reasoning, especially the use of SWRL rules, has not been widely used in biomedicine.

Results: We have built a knowledge base of human pseudogenes, extending the existing SO framework to incorporate additional attributes. In particular, we have defined the relationships between pseudogenes and segmental duplications. We then created a series of logical rules using SWRL to answer research questions and to annotate our pseudogenes appropriately. Finally, we were left with a knowledge base which could be queried to discover information about human pseudogene evolution.

Availability: The fully populated knowledge base described in this document is available for download from http://ontology.pseudogene.org. A SPARQL endpoint from which to query the dataset is also available at this location.

Contact:  matthew.holford@yale.edu; mark.gerstein@yale.edu
A dynamic Bayesian network for identifying protein-binding footprints from single molecule-based sequencing data
Authors: Chen Xiaoyu , Hoffman Michael M. , Bilmes Jeff A. , Hesselberth Jay R. , Noble William S.
Published: June 2010

Motivation: A global map of transcription factor binding sites (TFBSs) is critical to understanding gene regulation and genome function. DNaseI digestion of chromatin coupled with massively parallel sequencing (digital genomic footprinting) enables the identification of protein-binding footprints with high resolution on a genome-wide scale. However, accurately inferring the locations of these footprints remains a challenging computational problem.

Results: We present a dynamic Bayesian network-based approach for the identification and assignment of statistical confidence estimates to protein-binding footprints from digital genomic footprinting data. The method, DBFP, allows footprints to be identified in a probabilistic framework and outperforms our previously described algorithm in terms of precision at a fixed recall. Applied to a digital footprinting data set from Saccharomyces cerevisiae, DBFP identifies 4679 statistically significant footprints within intergenic regions. These footprints are mainly located near transcription start sites and are strongly enriched for known TFBSs. Footprints containing no known motif are preferentially located proximal to other footprints, consistent with cooperative binding of these footprints. DBFP also identifies a set of statistically significant footprints in the yeast coding regions. Many of these footprints coincide with the boundaries of antisense transcripts, and the most significant footprints are enriched for binding sites of the chromatin-associated factors Abf1 and Rap1.

Contact:  jay.hesselberth@ucdenver.edu; william-noble@u.washington.edu

Supplementary information:  Supplementary material is available at Bioinformatics online.
Drug-target interaction prediction from chemical, genomic and pharmacological data in an integrated framework
Authors: Yamanishi Yoshihiro , Kotera Masaaki , Kanehisa Minoru , Goto Susumu
Published: June 2010

Motivation:  In silico prediction of drug–target interactions from heterogeneous biological data is critical in the search for drugs and therapeutic targets for known diseases such as cancers. There is therefore a strong incentive to develop new methods capable of detecting these potential drug–target interactions efficiently.

Results: In this article, we investigate the relationship between the chemical space, the pharmacological space and the topology of drug–target interaction networks, and show that drug–target interactions are more correlated with pharmacological effect similarity than with chemical structure similarity. We then develop a new method to predict unknown drug–target interactions from chemical, genomic and pharmacological data on a large scale. The proposed method consists of two steps: (i) prediction of pharmacological effects from chemical structures of given compounds and (ii) inference of unknown drug–target interactions based on the pharmacological effect similarity in the framework of supervised bipartite graph inference. The originality of the proposed method lies in the prediction of potential pharmacological similarity for any drug candidate compounds and in the integration of chemical, genomic and pharmacological data in a unified framework. In the results, we make predictions for four classes of important drug–target interactions involving enzymes, ion channels, GPCRs and nuclear receptors. Our comprehensively predicted drug–target interaction networks enable us to suggest many potential drug–target interactions and to increase research productivity toward genomic drug discovery.

Supplementary information: Datasets and all prediction results are available at http://cbio.ensmp.fr/~yyamanishi/pharmaco/.

Availability: Softwares are available upon request.

Contact:  yoshihiro.yamanishi@ensmp.fr
A soft kinetic data structure for lesion border detection
Authors: Kockara Sinan , Mete Mutlu , Yip Vincent , Lee Brendan , Aydin Kemal
Published: June 2010

Motivation: The medical imaging and image processing techniques, ranging from microscopic to macroscopic, has become one of the main components of diagnostic procedures to assist dermatologists in their medical decision-making processes. Computer-aided segmentation and border detection on dermoscopic images is one of the core components of diagnostic procedures and therapeutic interventions for skin cancer. Automated assessment tools for dermoscopic images have become an important research field mainly because of inter- and intra-observer variations in human interpretations. In this study, a novel approach—graph spanner—for automatic border detection in dermoscopic images is proposed. In this approach, a proximity graph representation of dermoscopic images in order to detect regions and borders in skin lesion is presented.

Results: Graph spanner approach is examined on a set of 100 dermoscopic images whose manually drawn borders by a dermatologist are used as the ground truth. Error rates, false positives and false negatives along with true positives and true negatives are quantified by digitally comparing results with manually determined borders from a dermatologist. The results show that the highest precision and recall rates obtained to determine lesion boundaries are 100%. However, accuracy of assessment averages out at 97.72% and borders errors' mean is 2.28% for whole dataset.

Contact:  skockara@uca.edu
Complex event extraction at PubMed scale
Authors: Björne Jari , Ginter Filip , Pyysalo Sampo , Tsujii Jun'ichi , Salakoski Tapio
Published: June 2010

Motivation: There has recently been a notable shift in biomedical information extraction (IE) from relation models toward the more expressive event model, facilitated by the maturation of basic tools for biomedical text analysis and the availability of manually annotated resources. The event model allows detailed representation of complex natural language statements and can support a number of advanced text mining applications ranging from semantic search to pathway extraction. A recent collaborative evaluation demonstrated the potential of event extraction systems, yet there have so far been no studies of the generalization ability of the systems nor the feasibility of large-scale extraction.

Results: This study considers event-based IE at PubMed scale. We introduce a system combining publicly available, state-of-the-art methods for domain parsing, named entity recognition and event extraction, and test the system on a representative 1% sample of all PubMed citations. We present the first evaluation of the generalization performance of event extraction systems to this scale and show that despite its computational complexity, event extraction from the entire PubMed is feasible. We further illustrate the value of the extraction approach through a number of analyses of the extracted information.

Availability: The event detection system and extracted data are open source licensed and available at http://bionlp.utu.fi/.

Contact:  jari.bjorne@utu.fi
Efficient genome ancestry inference in complex pedigrees with inbreeding
Authors: Liu Eric Yi , Zhang Qi , McMillan Leonard , de Villena Fernando Pardo-Manuel , Wang Wei
Published: June 2010

Motivation: High-density SNP data of model animal resources provides opportunities for fine-resolution genetic variation studies. These genetic resources are generated through a variety of breeding schemes that involve multiple generations of matings derived from a set of founder animals. In this article, we investigate the problem of inferring the most probable ancestry of resulting genotypes, given a set of founder genotypes. Due to computational difficulty, existing methods either handle only small pedigree data or disregard the pedigree structure. However, large pedigrees of model animal resources often contain repetitive substructures that can be utilized in accelerating computation.

Results: We present an accurate and efficient method that can accept complex pedigrees with inbreeding in inferring genome ancestry. Inbreeding is a commonly used process in generating genetically diverse and reproducible animals. It is often carried out for many generations and can account for most of the computational complexity in real-world model animal pedigrees. Our method builds a hidden Markov model that derives the ancestry probabilities through inbreeding process without explicit modeling in every generation. The ancestry inference is accurate and fast, independent of the number of generations, for model animal resources such as the Collaborative Cross (CC). Experiments on both simulated and real CC data demonstrate that our method offers comparable accuracy to those methods that build an explicit model of the entire pedigree, but much better scalability with respect to the pedigree size.

Contact:  weiwang@cs.unc.edu
Multi-population GWA mapping via multi-task regularized regression
Authors: Puniyani Kriti , Kim Seyoung , Xing Eric P.
Published: June 2010

Motivation: Population heterogeneity through admixing of different founder populations can produce spurious associations in genome- wide association studies that are linked to the population structure rather than the phenotype. Since samples from the same population generally co-evolve, different populations may or may not share the same genetic underpinnings for the seemingly common phenotype. Our goal is to develop a unified framework for detecting causal genetic markers through a joint association analysis of multiple populations.

Results: Based on a multi-task regression principle, we present a multi-population group lasso algorithm using L1/L2-regularized regression for joint association analysis of multiple populations that are stratified either via population survey or computational estimation. Our algorithm combines information from genetic markers across populations, to identify causal markers. It also implicitly accounts for correlations between the genetic markers, thus enabling better control over false positive rates. Joint analysis across populations enables the detection of weak associations common to all populations with greater power than in a separate analysis of each population. At the same time, the regression-based framework allows causal alleles that are unique to a subset of the populations to be correctly identified. We demonstrate the effectiveness of our method on HapMap-simulated and lactase persistence datasets, where we significantly outperform state of the art methods, with greater power for detecting weak associations and reduced spurious associations.

Availability: Software will be available at http://www.sailing.cs.cmu.edu/

Contact:  epxing@cs.cmu.edu
Low-homology protein threading
Authors: Peng Jian , Xu Jinbo
Published: June 2010

Motivation: The challenge of template-based modeling lies in the recognition of correct templates and generation of accurate sequence-template alignments. Homologous information has proved to be very powerful in detecting remote homologs, as demonstrated by the state-of-the-art profile-based method HHpred. However, HHpred does not fare well when proteins under consideration are low-homology. A protein is low-homology if we cannot obtain sufficient amount of homologous information for it from existing protein sequence databases.

Results: We present a profile-entropy dependent scoring function for low-homology protein threading. This method will model correlation among various protein features and determine their relative importance according to the amount of homologous information available. When proteins under consideration are low-homology, our method will rely more on structure information; otherwise, homologous information. Experimental results indicate that our threading method greatly outperforms the best profile-based method HHpred and all the top CASP8 servers on low-homology proteins. Tested on the CASP8 hard targets, our threading method is also better than all the top CASP8 servers but slightly worse than Zhang-Server. This is significant considering that Zhang-Server and other top CASP8 servers use a combination of multiple structure-prediction techniques including consensus method, multiple-template modeling, template-free modeling and model refinement while our method is a classical single-template-based threading method without any post-threading refinement.

Contact:  jinboxu@gmail.com
Fragment-free approach to protein folding using conditional neural fields
Authors: Zhao Feng , Peng Jian , Xu Jinbo
Published: June 2010

Motivation: One of the major bottlenecks with ab initio protein folding is an effective conformation sampling algorithm that can generate native-like conformations quickly. The popular fragment assembly method generates conformations by restricting the local conformations of a protein to short structural fragments in the PDB. This method may limit conformations to a subspace to which the native fold does not belong because (i) a protein with really new fold may contain some structural fragments not in the PDB and (ii) the discrete nature of fragments may prevent them from building a native-like fold. Previously we have developed a conditional random fields (CRF) method for fragment-free protein folding that can sample conformations in a continuous space and demonstrated that this CRF method compares favorably to the popular fragment assembly method. However, the CRF method is still limited by its capability of generating conformations compatible with a sequence.

Results: We present a new fragment-free approach to protein folding using a recently invented probabilistic graphical model conditional neural fields (CNF). This new CNF method is much more powerful than CRF in modeling the sophisticated protein sequence-structure relationship and thus, enables us to generate native-like conformations more easily. We show that when coupled with a simple energy function and replica exchange Monte Carlo simulation, our CNF method can generate decoys much better than CRF on a variety of test proteins including the CASP8 free-modeling targets. In particular, our CNF method can predict a correct fold for T0496_D1, one of the two CASP8 targets with truly new fold. Our predicted model for T0496 is significantly better than all the CASP8 models.

Contact:  jinboxu@gmail.com
Modularity and directionality in genetic interaction maps
Authors: Jaimovich Ariel , Rinott Ruty , Schuldiner Maya , Margalit Hanah , Friedman Nir
Published: June 2010

Motivation: Genetic interactions between genes reflect functional relationships caused by a wide range of molecular mechanisms. Large-scale genetic interaction assays lead to a wealth of information about the functional relations between genes. However, the vast number of observed interactions, along with experimental noise, makes the interpretation of such assays a major challenge.

Results: Here, we introduce a computational approach to organize genetic interactions and show that the bulk of observed interactions can be organized in a hierarchy of modules. Revealing this organization enables insights into the function of cellular machineries and highlights global properties of interaction maps. To gain further insight into the nature of these interactions, we integrated data from genetic screens under a wide range of conditions to reveal that more than a third of observed aggravating (i.e. synthetic sick/lethal) interactions are unidirectional, where one gene can buffer the effects of perturbing another gene but not vice versa. Furthermore, most modules of genes that have multiple aggravating interactions were found to be involved in such unidirectional interactions. We demonstrate that the identification of external stimuli that mimic the effect of specific gene knockouts provides insights into the role of individual modules in maintaining cellular integrity.

Availability: We designed a freely accessible web tool that includes all our findings, and is specifically intended to allow effective browsing of our results (http://compbio.cs.huji.ac.il/GIAnalysis).

Contact:  maya.schuldiner@weizmann.ac.il; hanahm@ekmd.huji.ac.il; nir@cs.huji.ac.il

Supplementary information:  Supplementary data are available at Bioinformatics online.
Close lower and upper bounds for the minimum reticulate network of multiple phylogenetic trees
Authors: Wu Yufeng
Published: June 2010

Motivation: Reticulate network is a model for displaying and quantifying the effects of complex reticulate processes on the evolutionary history of species undergoing reticulate evolution. A central computational problem on reticulate networks is: given a set of phylogenetic trees (each for some region of the genomes), reconstruct the most parsimonious reticulate network (called the minimum reticulate network) that combines the topological information contained in the given trees. This problem is well-known to be NP-hard. Thus, existing approaches for this problem either work with only two input trees or make simplifying topological assumptions.

Results: We present novel results on the minimum reticulate network problem. Unlike existing approaches, we address the fully general problem: there is no restriction on the number of trees that are input, and there is no restriction on the form of the allowed reticulate network. We present lower and upper bounds on the minimum number of reticulation events in the minimum reticulate network (and infer an approximately parsimonious reticulate network). A program called PIRN implements these methods, which also outputs a graphical representation of the inferred network. Empirical results on simulated and biological data show that our methods are practical for a wide range of data. More importantly, the lower and upper bounds match for many datasets (especially when the number of trees is small or reticulation level is low), and this allows us to solve the minimum reticulate network problem exactly for these datasets.

Availability: A software tool, PIRN, is available for download from the web page: http://www.engr.uconn.edu/~ywu.

Contact:  ywu@engr.uconn.edu

Supplementary information:  Supplementary data is available at Bioinformatics online.
Phylogenetic networks do not need to be complex: using fewer reticulations to represent conflicting clusters
Authors: van Iersel Leo , Kelk Steven , Rupp Regula , Huson Daniel
Published: June 2010

Phylogenetic trees are widely used to display estimates of how groups of species are evolved. Each phylogenetic tree can be seen as a collection of clusters, subgroups of the species that evolved from a common ancestor. When phylogenetic trees are obtained for several datasets (e.g. for different genes), then their clusters are often contradicting. Consequently, the set of all clusters of such a dataset cannot be combined into a single phylogenetic tree. Phylogenetic networks are a generalization of phylogenetic trees that can be used to display more complex evolutionary histories, including reticulate events, such as hybridizations, recombinations and horizontal gene transfers. Here, we present the new Cass algorithm that can combine any set of clusters into a phylogenetic network. We show that the networks constructed by Cass are usually simpler than networks constructed by other available methods. Moreover, we show that Cass is guaranteed to produce a network with at most two reticulations per biconnected component, whenever such a network exists. We have implemented Cass and integrated it into the freely available Dendroscope software.

Contact:  l.j.j.v.iersel@gmail.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
Time and memory efficient likelihood-based tree searches on phylogenomic alignments with missing data
Authors: Stamatakis Alexandros , Alachiotis Nikolaos
Published: June 2010

Motivation: The current molecular data explosion poses new challenges for large-scale phylogenomic analyses that can comprise hundreds or even thousands of genes. A property that characterizes phylogenomic datasets is that they tend to be gappy, i.e. can contain taxa with (many and disparate) missing genes. In current phylogenomic analyses, this type of alignment gappyness that is induced by missing data frequently exceeds 90%. We present and implement a generally applicable mechanism that allows for reducing memory footprints of likelihood-based [maximum likelihood (ML) or Bayesian] phylogenomic analyses proportional to the amount of missing data in the alignment. We also introduce a set of algorithmic rules to efficiently conduct tree searches via subtree pruning and re-grafting moves using this mechanism.

Results: On a large phylogenomic DNA dataset with 2177 taxa, 68 genes and a gappyness of 90%, we achieve a memory footprint reduction from 9 GB down to 1 GB, a speedup for optimizing ML model parameters of 11, and accelerate the Subtree Pruning Regrafting tree search phase by factor 16. Thus, our approach can be deployed to improve efficiency for the two most important resources, CPU time and memory, by up to one order of magnitude.

Availability: Current open-source version of RAxML v7.2.6 available at http://wwwkramer.in.tum.de/exelixis/software.html.

Contact:  stamatak@cs.tum.edu
TRStalker: an efficient heuristic for finding fuzzy tandem repeats
Authors: Pellegrini Marco , Renda M. Elena , Vecchio Alessio
Published: June 2010

Motivation: Genomes in higher eukaryotic organisms contain a substantial amount of repeated sequences. Tandem Repeats (TRs) constitute a large class of repetitive sequences that are originated via phenomena such as replication slippage and are characterized by close spatial contiguity. They play an important role in several molecular regulatory mechanisms, and also in several diseases (e.g. in the group of trinucleotide repeat disorders). While for TRs with a low or medium level of divergence the current methods are rather effective, the problem of detecting TRs with higher divergence (fuzzy TRs) is still open. The detection of fuzzy TRs is propaedeutic to enriching our view of their role in regulatory mechanisms and diseases. Fuzzy TRs are also important as tools to shed light on the evolutionary history of the genome, where higher divergence correlates with more remote duplication events.

Results: We have developed an algorithm (christened TRStalker) with the aim of detecting efficiently TRs that are hard to detect because of their inherent fuzziness, due to high levels of base substitutions, insertions and deletions. To attain this goal, we developed heuristics to solve a Steiner version of the problem for which the fuzziness is measured with respect to a motif string not necessarily present in the input string. This problem is akin to the ‘generalized median string’ that is known to be an NP-hard problem. Experiments with both synthetic and biological sequences demonstrate that our method performs better than current state of the art for fuzzy TRs and that the fuzzy TRs of the type we detect are indeed present in important biological sequences.

Availability: TRStalker will be integrated in the web-based TRs Discovery Service (TReaDS) at bioalgo.iit.cnr.it.

Contact:  marco.pellegrini@iit.cnr.it

Supplementary information:  Supplementary data are available at Bioinformatics online.
Automatic reconstruction of 3D neuron structures using a graph-augmented deformable model
Authors: Peng Hanchuan , Ruan Zongcai , Atasoy Deniz , Sternson Scott
Published: June 2010

Motivation: Digital reconstruction of 3D neuron structures is an important step toward reverse engineering the wiring and functions of a brain. However, despite a number of existing studies, this task is still challenging, especially when a 3D microscopic image has low single-to-noise ratio and discontinued segments of neurite patterns.

Results: We developed a graph-augmented deformable model (GD) to reconstruct (trace) the 3D structure of a neuron when it has a broken structure and/or fuzzy boundary. We formulated a variational problem using the geodesic shortest path, which is defined as a combination of Euclidean distance, exponent of inverse intensity of pixels along the path and closeness to local centers of image intensity distribution. We solved it in two steps. We first used a shortest path graph algorithm to guarantee that we find the global optimal solution of this step. Then we optimized a discrete deformable curve model to achieve visually more satisfactory reconstructions. Within our framework, it is also easy to define an optional prior curve that reflects the domain knowledge of a user. We investigated the performance of our method using a number of challenging 3D neuronal image datasets of different model organisms including fruit fly, Caenorhabditis elegans, and mouse. In our experiments, the GD method outperformed several comparison methods in reconstruction accuracy, consistency, robustness and speed. We further used GD in two real applications, namely cataloging neurite morphology of fruit fly to build a 3D ‘standard’ digital neurite atlas, and estimating the synaptic bouton density along the axons for a mouse brain.

Availability: The software is provided as part of the V3D-Neuron 1.0 package freely available at http://penglab.janelia.org/proj/v3d

Contact:  pengh@janelia.hhmi.org