bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental epigenomics: understanding the effects of parental care on the epigenome
Authors: McGowan Patrick O. , Szyf Moshe
Published: September 2010

An organism’s behavioural and physiological and social milieu influence and are influenced by the epigenome, which is comprised predominantly of chromatin and the covalent modification of DNA by methylation. Epigenetic patterns are sculpted during development to shape the diversity of gene expression programmes in the organism. In contrast with the genetic sequence, which is determined by inheritance and is virtually identical in all tissues, the epigenetic pattern varies from cell type to cell type and is potentially dynamic throughout life. It is postulated that different environmental exposures could effect epigenetic patterns relevant for human behaviour. Because epigenetic programming defines the state of expression of genes, epigenetic differences could have the same consequences as genetic polymorphisms. Yet in contrast with genetic sequence differences, epigenetic alterations are potentially reversible. In the present chapter, we will discuss evidence that epigenetic processes early in life play a role in defining inter-individual trajectories of behaviour, with implications for mental health in adulthood.
Luminescence and creation of electron centers in UV-irradiated YAlO3 single crystals
Authors: Grigorjeva L. , Krasnikov A. , Laguta V. V. , Nikl M. , Zazubovich S.
Published: September 2010

Luminescence and defect creation processes were studied by the photoluminescence, thermally stimulated luminescence, and electron paramagnetic resonance methods in the UV-irradiated single crystals of undoped YAlO3, containing small amounts of Ce, Mo, and Ti ions as accidental impurities. The luminescence of the electron antisite YAl2+-type centers of different structures was found around 2.45 eV and studied at 4.2–500 K. The luminescence of the Ti3+-related centers (2.03 and 1.73 eV) and Ti4+ centers (2.78 eV) was observed as well. Dependences of the number of the YAl2+-type and Ti3+-related centers on the UV irradiation energy, temperature, and duration, as well as on various crystal heat-treatment procedures were examined. As a result of the photostimulated electron transfer from the O2− ligand ions to Mo4+ and Ti4+ ions, the paramagnetic hole O−-type centers and electron Ti3+ and Mo3+ centers are created. The antisite YAl2+-type centers are created due to the photostimulated release of electrons mainly from the Mo3+ centers to the conduction band and their subsequent trapping at the YAl3+ ions located near an oxygen vacancy or a defect at the neighboring Y3+ site.
Stability of liquid sheet edges
Authors: Krechetnikov R.
Published: September 2010

Accelerating edges of thin liquid sheets are ubiquitous and are known to experience a longitudinal (along-the-edge) instability, which often leads to their break-up and atomization. The fundamental physical mechanisms of this instability are studied analytically in the quasisteady regime, which admits a concise modeling. It is discovered that the classical Rayleigh–Taylor mechanism is substantially modified which leads to a stability picture different from that for flat interfaces, in part due to an interplay with Rayleigh–Plateau mechanisms. In particular, as the Bond number increases, first, only one critical wavenumber is excited, but for higher values of the Bond number several critical wavenumbers can coexist with the same growth rates. This allows for the transition from the regular picture, in which one wavelength sets the pattern, to the frustrated picture, in which a few wavenumbers compete with each other.
Pyroelectric properties of barium strontium titanate films: Effect of thermal stresses
Authors: Zhang J. , Cole M. W. , Alpay S. P.
Published: September 2010

A nonlinear thermodynamic model is used to investigate the influence of thermal stresses on the room temperature (RT) pyroelectric properties of (001)-textured polycrystalline barium strontium titanate (BaxSr1−xTiO3, BST) films with four different compositions on three integrated circuit-friendly substrates: Si, (0001) and (1¯1¯20) sapphire. It is found that the in-plane tensile thermal strain in BST increases with increasing deposition/processing temperature TG due to the difference of thermal expansion coefficients between the BST film and the selected substrate materials. Considering the variations in the ferroelectric phase transformation due to thermal strains, our findings show that relatively lower processing temperatures would result in better pyroelectric response. For BST 60/40 and 70/30 on all the substrates, the film is in the paraelectric state for TG=25–800 °C and the pyroelectric response is due to the interplay of the electric field and thermal strain dependence of the dielectric constant and the TG-dependence of the thermal strains. While the RT pyroelectric response of these films is expected to be relatively low (0.02–0.05 μC/cm2 K at ∼200 kV/cm), at high applied fields the pyroelectric properties do not display a significant dependence on the temperature at which the material was treated. On the other hand, BST 80/20 and BST 90/10 films may be in the ferroelectric state at RT depending on TG. If TG can be adjusted such that the ferroelectric phase transformation is near RT, a relatively high bulklike pyroelectric response (>0.5–1.0 μC/cm2 K) can be realized. However, the pyroelectric coefficient decreases sharply above and below these “critical” TG, and thus a precise temperature control during processing would be required.
Two dimensional electron gases in polycrystalline MgZnO/ZnO heterostructures grown by rf-sputtering process
Authors: Chin Huai-An , Cheng I-Chun , Huang Chih-I , Wu Yuh-Renn , Lu Wen-Sen , Lee Wei-Li , Chen Jian Z. , Chiu Kuo-Chuang , Lin Tzer-Shen
Published: September 2010

This paper reports the formation of two-dimensional electron gas (2DEG) in rf-sputtered defective polycrystalline MgZnO/ZnO heterostructure via the screening of grain boundary potential by polarization-induced charges. As the MgZnO thickness increases, the sheet resistance reduces rapidly and then saturates. The enhancement of the interfacial polarization effect becomes stronger, corresponding to a larger amount of resistance reduction, when the Mg content in the cap layer increases. Monte Carlo method by including grain boundary scattering effect as well as 2D finite-element-method Poisson and drift-diffusion solver is applied to analyze the polycrystalline heterostructure. The experimental and Monte Carlo simulation results show good agreement. From low temperature Hall measurement, the carrier density and mobility are both independent of temperature, indicating the formation of 2DEG with roughness scattering at the MgZnO/ZnO interface.
Transparency pump intensity and differential gain in resonantly pumped W optical pumping injection cavity lasers
Authors: Olafsen L. J. , McAlpine T. C.
Published: September 2010

We report the results of a cavity length characterization of a W optical pumping injection cavity (OPIC) laser with a room temperature emission wavelength of 3.2 μm using pump wavelength tuning to achieve resonant optical pumping. Devices with cavity lengths ranging from 312 to 2030 μm are characterized to determine geometry-independent figures of merit. The measurements yield transparency pump intensities Itr that range from 230 W/cm2 at 100 K to 7.8 kW/cm2 at 300 K, as gain per unit pump intensity (differential gain) decreases from 0.17 cm/W at 100 K to 0.011 cm/W at 300 K. The characteristic temperature of the transparency pump intensity is 55.6 K, while the gain per unit pump intensity demonstrates an exponential decay with a characteristic temperature of 67.9 K. Compared to other optically pumped type-II W lasers and electrically injected interband cascade lasers, there is less reduction in the differential gain with increasing temperature, consistent with the high temperature operation of these OPIC devices.
Numerical simulation of charge transport in disordered organic semiconductor devices
Authors: Knapp E. , Häusermann R. , Schwarzenbach H. U. , Ruhstaller B.
Published: September 2010

For the design of organic semiconductor devices such as organic light-emitting devices and solar cells, it is of crucial importance to solve the underlying charge transport equations efficiently and accurately. Only a fast and robust solver allows the use of fitting algorithms for parameter extraction and variation. Introducing appropriate models for organic semiconductors that account for the disordered nature of hopping transport leads to increasingly nonlinear and more strongly coupled equations. The solution procedures we present in this study offer a versatile, robust, and efficient means of simulating organic semiconductor devices. They allow for the direct solution of the steady-state drift-diffusion problem. We demonstrate that the numerical methods perform well in combination with advanced physical transport models such as energetic Gaussian disorder, density-dependent and field-dependent mobilities, the generalized Einstein diffusion, traps, and its consistent charge injection model.
Desorption kinetics of GeO from GeO2/Ge structure
Authors: Wang Sheng Kai , Kita Koji , Lee Choong Hyun , Tabata Toshiyuki , Nishimura Tomonori , Nagashio Kosuke , Toriumi Akira
Published: September 2010

High-κ dielectrics on Ge have recently attracted much attention as a potential candidate to replace planar silicon transistors for sub-32-nm generations. However, the instability of the high-κ/Ge interface, especially the desorption of germanium monoxide (GeO), hampers the development of Ge-based devices. Therefore, the typical GeO2/Ge structure was chosen to investigate GeO desorption. In this contribution, we describe the desorption kinetics of GeO, including Ge/GeO2 interface reaction, the diffusion process during GeO desorption, the desorption activation energy of GeO, the different mechanisms of GeO desorption, and the active oxidation of Ge. Through annealing GeO2/Ge in an ultrahigh vacuum (UHV), direct evidence for the consumption of Ge substrate has been shown by atomic force microscopy (AFM) measurements of the consumption depth. By using thermal desorption spectroscopy (TDS) measurements and studying oxygen-18 isotope tracing, we have clarified that the GeO desorption is not caused by the GeO direct-diffusion process. Isothermal TDS measurements and morphology investigation have revealed a transition from a uniform desorption mechanism to a nonuniform one as GeO2 thickness was reduced. On the basis of the experimental results in this study, a GeO desorption model has been developed. For GeO desorption, about 2 eV of activation energy has been obtained from kinetic calculation on the basis of TDS analysis. Different from the UHV annealing, the active oxidation of Ge has been observed by AFM measurements under low oxygen partial pressures.
Intrinsic ferromagnetism and magnetic anisotropy in Gd-doped ZnO thin films synthesized by pulsed spray pyrolysis method
Authors: Subramanian M. , Thakur P. , Tanemura M. , Hihara T. , Ganesan V. , Soga T. , Chae K. H. , Jayavel R. , Jimbo T.
Published: September 2010

This paper reports an in-depth study on nanocrystalline Gd-doped ZnO thin films synthesized using versatile pulsed spray pyrolysis method and exhibit room temperature ferromagnetism. The detailed structural and microstructural studies confirm that the doped Gd ions occupy Zn sites and the peak shift can be elucidated by charge neutrality. Optical investigation shows that the Gd doping in ZnO lattice leads to a decrease in the near band edge position due to the introduction of new unoccupied states by Gd 4f electrons. The electronic structure of the Zn1−xGdxO at the O K edge shows the evolution of pre-edge spectral features similar to cuprates and manganites, and also confirms the strong hybridization of O 2p–Gd 4f/5d states. Furthermore, the Gd M5 edge provides evidence that Gd ions are in the trivalent state. Hysteresis measurements demonstrate that the Gd-doped ZnO films are magnetically anisotropic and exhibit intrinsic ferromagnetic behavior at room temperature. Higher magnetization in 3 kOe values is observed for a field applied perpendicular to the sample surface compared to the in-plane direction.
A commutant of βγ-system associated to the highest weight module V4 of sl(2,C)
Authors: Chu Yan-Jun , Huang Fang , Zheng Zhu-Jun
Published: September 2010

Analogous to the commutant in the theory of associative algebras, one can construct a new subalgebra of a vertex algebra, known as the vertex algebra commutant. In this paper, for the highest weight module V4 of Lie algebra sl(2,C), we describe a commutant of βγ-system S(V4) by giving a finite set of generators and operator product expansion relations among generators.
Exceptional quantum subgroups for the rank two Lie algebras B2 and G2
Authors: Coquereaux R. , Rais R. , Tahri E. H.
Published: September 2010

Exceptional modular invariants for the Lie algebras B2 (at levels 2, 3, 7, and 12) and G2 (at levels 3 and 4) can be obtained from conformal embeddings. We determine the associated algebras of quantum symmetries and discover or recover, as a by-product, the graphs describing exceptional quantum subgroups of type B2 or G2 that encode their module structure over the associated fusion category. Global dimensions are given.
Optimal observables for minimum-error state discrimination in general probabilistic theories
Authors: Nuida Koji , Kimura Gen , Miyadera Takayuki
Published: September 2010

General probabilistic theories provide the most general mathematical framework for the theory of probability in an operationally natural manner and generalize classical and quantum theories. In this article, we study state discrimination problems in general probabilistic theories using a Bayesian strategy. After reformulation of the theories with mathematical rigor, we first prove that an optimal observable to discriminate any (finite) number of states always exists in the most general setting. Next, we revisit our recently proposed geometric approach for the problem and show that for two-state discrimination, this approach is indeed effective in arbitrary dimensional cases. Moreover, our method reveals an operational meaning of Gudder’s “intrinsic metric” by means of the optimal success probability, which turns out to be a generalization of the trace distance for quantum systems. As its by-product, an information disturbance theorem in general probabilistic theories is derived, generalizing its well known quantum version.
Molecular chemisorption on open metal sites in Cu3(benzenetricarboxylate)2: A spatially periodic density functional theory study
Authors: Watanabe Taku , Sholl David S.
Published: September 2010

Chemical interactions of H2O, CO, NO, pyridine, C2H2, H2S, and NH3 with open metal sites in the metal-organic framework (MOF) Cu3(benzenetricarboxylate)2 are examined using plane wave periodic density functional theory (DFT). In the case of single molecule adsorption on a Cu dimer, NH3 and pyridine have the strongest binding, while NO binds weakly. Binding of pairs of molecules on a Cu dimer shows significant interaction energies, that is, the binding energy of the pair of molecules is not a simple summation of the binding energies of each molecule. The effect of molecular adsorption on the magnetic moments of Cu atoms in the MOF is also examined. Using the binding energies from DFT calculations, the effects of the pressure and temperature on the chemisorbed species are investigated. Finally the effect of water adsorption on the elastic behavior of Cu3(BTC)2 is described.
Subwavelength electromagnetic energy transport by stack of metallic nanorings
Authors: Jafari M. R. , Ebrahimi F. , Nooshirvani M.
Published: September 2010

In this paper, we consider linear ordered stack of metallic nanorings in the presence of Aharonov–Bohm magnetic flux for externally tunable electromagnetic energy transport below the diffraction limit. Using random phase approximation, we demonstrate that such structure supports propagating surface plasmon modes with negative group velocities and with magnetic flux dependent frequencies. Our results for dispersion relations, bandwidths, and tunabilities of surface plasmon modes give an explicit demonstration that nanoring based subwavelength waveguides are potential candidate for electromagnetic energy transport below the diffraction limit in the terahertz part of spectrum.
Physical origin of the third order nonlinear optical response of orthogonal pyrrolo-tetrathiafulvalene derivatives
Authors: Iliopoulos K. , Czaplicki R. , El Ouazzani H. , Balandier J. Y. , Chas M. , Goeb S. , Sallé M. , Gindre D. , Sahraoui B.
Published: September 2010

We present the third order nonlinear optical study of tetrathiafulvalene-based molecular corners. Degenerate four-wave mixing measurements have been done to provide information about the magnitude and the origin of the nonlinearity, while the nonlinear absorption has been separately measured by performing “open aperture” Z-scan measurements. The response has been found to be strongly dependent upon the structure of the molecular corners.
Low frequency noise in InSb/GaAs and InSb/Si channels
Authors: Dobbert J. , Tran L. , Hatami F. , Masselink W. T. , Kunets Vas. P. , Salamo G. J.
Published: September 2010

The low frequency noise features of InSb grown on GaAs and Si substrates using molecular-beam epitaxy are investigated in the temperature range from 80 to 300 K. In all samples the flicker noise dominates the spectra, with Hooge factors as low as 2×10−5 and 9×10−5 for InSb on GaAs and Si, respectively. The temperature dependence of the Hooge factors is investigated.
Cellular network formation of hydrophobic alkanethiol capped gold nanoparticles on mica surface mediated by water islands
Authors: John Neena S. , Raina Gargi , Sharma Ashutosh , Kulkarni Giridhar U.
Published: September 2010

Dendritic and cellular networks of nanoparticles are known to form commonly either by random diffusion-limited aggregation or by solvent evaporation dynamics. Using alkanethiol capped gold nanoparticles deposited on mica imaged under ambient and controlled water vapor conditions by atomic force microscope and in situ scanning electron microscope, respectively, we show a third mechanism in action. The cellular network consisting of open and closed polygons is formed by the nucleation and lateral growth of adsorbed water islands, the contact lines of which push the randomly distributed hydrophobic nanoparticles along the growth directions, eventually leading to the polygonal structure formation as the boundaries of the growing islands meet. Such nanoparticle displacement has been possible due to the weakly adhering nature of the hydrophilic substrate, mica. These results demonstrate an important but hitherto neglected effect of adsorbed water in the structure formation on hydrophilic substrates and provide a facile tool for the fabrication of nanoparticle networks without specific particle or substrate modifications and without a tight control on particle deposition conditions during the solvent evaporation.
Switching field distribution and transition width in energy assisted magnetic recording
Authors: Wang Xiaobin , Gao Kai-Zhong , Hohlfeld Julius , Seigler Mike
Published: September 2010

In order to achieve higher areal density, magnetization transition width must be reduced. This requires small media switching field distribution (SFD). Here we explore SFD and transition width in heat assisted magnetic recording and microwave assisted magnetic recording. We reveal that for energy assisted magnetic recording, additional SFD broadening exists as compare to conventional perpendicular recording. We show the effect of SFD broadening on transition width and the implications to the magnetic recording system as the areal density increases.
Blood flow velocity imaging of malignant melanoma by micro multipoint laser Doppler velocimetry
Authors: Ishida H. , Andoh T. , Akiguchi S. , Shirakawa H. , Kobayashi D. , Kuraishi Y. , Hachiga T.
Published: September 2010

We have developed a laser Doppler velocimeter to measure blood flow, the micromultipoint laser Doppler velocimeter (μ-MLDV). This equipment can measure absolute velocity and, based on this, can display the course of blood vessels. In this study, we attempted to perform blood flow velocity imaging of malignant melanoma transplanted to the mouse ear. We found that blood flow velocity of the formed blood vessels originating in the melanoma was much greater than that of the capillary vessels in normal skin. Furthermore, the form of the tumor was clearly visible from the blood flow velocity image. These experimental results suggest that μ-MLDV has potential as a diagnostic method for distinguishing benign nevi from malignant melanomas.
A piezoelectric bistable plate for nonlinear broadband energy harvesting
Authors: Arrieta A. F. , Hagedorn P. , Erturk A. , Inman D. J.
Published: September 2010

Recently, the idea of using nonlinearity to enhance the performance of vibration-based energy harvesters has been investigated. Nonlinear energy harvesting devices have been shown to be capable of operating over wider frequency ranges delivering more power than their linear counterparts, rendering them more suitable for real applications. In this paper, we propose to exploit the rich nonlinear behavior of a bistable composite plate with bonded piezoelectric patches for broadband nonlinear energy harvesting. The response of the structure is experimentally investigated revealing different large amplitude oscillations. Substantially large power is extracted over a wide frequency range achieving broadband nonlinear energy harvesting.
Inflammatory dendritic cells—not basophils—are necessary and sufficient for induction of Th2 immunity to inhaled house dust mite allergen
Authors: Hammad Hamida , Plantinga Maud , Deswarte Kim , Pouliot Philippe , Willart Monique A.M. , Kool Mirjam , Muskens Femke , Lambrecht Bart N.
Published: September 2010

It is unclear how Th2 immunity is induced in response to allergens like house dust mite (HDM). Here, we show that HDM inhalation leads to the TLR4/MyD88-dependent recruitment of IL-4 competent basophils and eosinophils, and of inflammatory DCs to the draining mediastinal nodes. Depletion of basophils only partially reduced Th2 immunity, and depletion of eosinophils had no effect on the Th2 response. Basophils did not take up inhaled antigen, present it to T cells, or express antigen presentation machinery, whereas a population of FceRI+ DCs readily did. Inflammatory DCs were necessary and sufficient for induction of Th2 immunity and features of asthma, whereas basophils were not required. We favor a model whereby DCs initiate and basophils amplify Th2 immunity to HDM allergen.
A fast algorithm for exact sequence search in biological sequences using polyphase decomposition
Authors: Srikantha Abhilash , Bopardikar Ajit S. , Kaipa Kalyan Kumar , Venkataraman Parthasarathy , Lee Kyusang , Ahn TaeJin , Narayanan Rangavittal
Published: September 2010

Motivation: Exact sequence search allows a user to search for a specific DNA subsequence in a larger DNA sequence or database. It serves as a vital block in many areas such as Pharmacogenetics, Phylogenetics and Personal Genomics. As sequencing of genomic data becomes increasingly affordable, the amount of sequence data that must be processed will also increase exponentially. In this context, fast sequence search algorithms will play an important role in exploiting the information contained in the newly sequenced data. Many existing algorithms do not scale up well for large sequences or databases because of their high-computational costs. This article describes an efficient algorithm for performing fast searches on large DNA sequences. It makes use of hash tables of Q-grams that are constructed after downsampling the database, to enable efficient search and memory use. Time complexity for pattern search is reduced using beam pruning techniques. Theoretical complexity calculations and performance figures are presented to indicate the potential of the proposed algorithm.

Contact:  s.abhilash@samsung.com; ajit.b@samsung.com
Characteristics of 454 pyrosequencing data—enabling realistic simulation with flowsim
Authors: Balzer Susanne , Malde Ketil , Lanzén Anders , Sharma Animesh , Jonassen Inge
Published: September 2010

Motivation: The commercial launch of 454 pyrosequencing in 2005 was a milestone in genome sequencing in terms of performance and cost. Throughout the three available releases, average read lengths have increased to ∼500 base pairs and are thus approaching read lengths obtained from traditional Sanger sequencing. Study design of sequencing projects would benefit from being able to simulate experiments.

Results: We explore 454 raw data to investigate its characteristics and derive empirical distributions for the flow values generated by pyrosequencing. Based on our findings, we implement Flowsim, a simulator that generates realistic pyrosequencing data files of arbitrary size from a given set of input DNA sequences. We finally use our simulator to examine the impact of sequence lengths on the results of concrete whole-genome assemblies, and we suggest its use in planning of sequencing projects, benchmarking of assembly methods and other fields.

Availability: Flowsim is freely available under the General Public License from http://blog.malde.org/index.php/flowsim/

Contact:  susanne.balzer@imr.no; ketil.malde@imr.no
Integrating genome assemblies with MAIA
Authors: Nijkamp Jurgen , Winterbach Wynand , van den Broek Marcel , Daran Jean-Marc , Reinders Marcel , de Ridder Dick
Published: September 2010

Motivation:  De novo assembly of a eukaryotic genome with next-generation sequencing data is still a challenging task. Over the past few years several assemblers have been developed, often suitable for one specific type of sequencing data. The number of known genomes is expanding rapidly, therefore it becomes possible to use multiple reference genomes for assembly projects. We introduce an assembly integrator that makes use of all available data, i.e. multiple de novo assemblies and mappings against multiple related genomes, by optimizing a weighted combination of criteria.

Results: The developed algorithm was applied on the de novo sequencing of the Saccharomyces cerevisiae CEN.PK 113-7D strain. Using Solexa and 454 read data, two de novo and three comparative assemblies were constructed and subsequently integrated, yielding 29 contigs, covering more than 12 Mbp; a drastic improvement compared with the single assemblies.

Availability: MAIA is available as a Matlab package and can be downloaded from http://bioinformatics.tudelft.nl

Contact:  j.f.nijkamp@tudelft.nl
Discriminatory power of RNA family models
Authors: Siederdissen Christian Höner zu , Hofacker Ivo L.
Published: September 2010

Motivation: RNA family models group nucleotide sequences that share a common biological function. These models can be used to find new sequences belonging to the same family. To succeed in this task, a model needs to exhibit high sensitivity as well as high specificity. As model construction is guided by a manual process, a number of problems can occur, such as the introduction of more than one model for the same family or poorly constructed models. We explore the Rfam database to discover such problems.

Results: Our main contribution is in the definition of the discriminatory power of RNA family models, together with a first algorithm for its computation. In addition, we present calculations across the whole Rfam database that show several families lacking high specificity when compared to other families. We give a list of these clusters of families and provide a tentative explanation. Our program can be used to: (i) make sure that new models are not equivalent to any model already present in the database; and (ii) new models are not simply submodels of existing families.

Availability:  www.tbi.univie.ac.at/software/cmcompare/. The code is licensed under the GPLv3. Results for the whole Rfam database and supporting scripts are available together with the software.

Contact:  choener@tbi.univie.ac.at
Nonlinear dimension reduction and clustering by Minimum Curvilinearity unfold neuropathic pain and tissue embryological classes
Authors: Cannistraci Carlo Vittorio , Ravasi Timothy , Montevecchi Franco Maria , Ideker Trey , Alessio Massimo
Published: September 2010

Motivation: Nonlinear small datasets, which are characterized by low numbers of samples and very high numbers of measures, occur frequently in computational biology, and pose problems in their investigation. Unsupervised hybrid-two-phase (H2P) procedures—specifically dimension reduction (DR), coupled with clustering—provide valuable assistance, not only for unsupervised data classification, but also for visualization of the patterns hidden in high-dimensional feature space.

Methods: ‘Minimum Curvilinearity’ (MC) is a principle that—for small datasets—suggests the approximation of curvilinear sample distances in the feature space by pair-wise distances over their minimum spanning tree (MST), and thus avoids the introduction of any tuning parameter. MC is used to design two novel forms of nonlinear machine learning (NML): Minimum Curvilinear embedding (MCE) for DR, and Minimum Curvilinear affinity propagation (MCAP) for clustering.

Results: Compared with several other unsupervised and supervised algorithms, MCE and MCAP, whether individually or combined in H2P, overcome the limits of classical approaches. High performance was attained in the visualization and classification of: (i) pain patients (proteomic measurements) in peripheral neuropathy; (ii) human organ tissues (genomic transcription factor measurements) on the basis of their embryological origin.

Conclusion: MC provides a valuable framework to estimate nonlinear distances in small datasets. Its extension to large datasets is prefigured for novel NMLs. Classification of neuropathic pain by proteomic profiles offers new insights for future molecular and systems biology characterization of pain. Improvements in tissue embryological classification refine results obtained in an earlier study, and suggest a possible reinterpretation of skin attribution as mesodermal.

Availability:  https://sites.google.com/site/carlovittoriocannistraci/home

Contact:  kalokagathos.agon@gmail.com; massimo.alessio@hsr.it

Supplementary information:  Supplementary data are available at Bioinformatics online.
is-rSNP: a novel technique forin silicoregulatory SNP detection
Authors: Macintyre Geoff , Bailey James , Haviv Izhak , Kowalczyk Adam
Published: September 2010

Motivation: Determining the functional impact of non-coding disease-associated single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) is challenging. Many of these SNPs are likely to be regulatory SNPs (rSNPs): variations which affect the ability of a transcription factor (TF) to bind to DNA. However, experimental procedures for identifying rSNPs are expensive and labour intensive. Therefore, in silico methods are required for rSNP prediction. By scoring two alleles with a TF position weight matrix (PWM), it can be determined which SNPs are likely rSNPs. However, predictions in this manner are noisy and no method exists that determines the statistical significance of a nucleotide variation on a PWM score.

Results: We have designed an algorithm for in silico rSNP detection called is-rSNP. We employ novel convolution methods to determine the complete distributions of PWM scores and ratios between allele scores, facilitating assignment of statistical significance to rSNP effects. We have tested our method on 41 experimentally verified rSNPs, correctly predicting the disrupted TF in 28 cases. We also analysed 146 disease-associated SNPs with no known functional impact in an attempt to identify candidate rSNPs. Of the 11 significantly predicted disrupted TFs, 9 had previous evidence of being associated with the disease in the literature. These results demonstrate that is-rSNP is suitable for high-throughput screening of SNPs for potential regulatory function. This is a useful and important tool in the interpretation of GWAS.

Availability: is-rSNP software is available for use at: www.genomics.csse.unimelb.edu.au/is-rSNP

Contact:  gmaci@csse.unimelb.edu.au; adam.kowalczyk@nicta.com.au

Supplementary information:  Supplementary data are available at Bioinformatics online.
A varying threshold method for ChIP peak-calling using multiple sources of information
Authors: Chen Kuan-Bei , Zhang Yu
Published: September 2010

Motivation: Gene regulation commonly involves interaction among DNA, proteins and biochemical conditions. Using chromatin immunoprecipitation (ChIP) technologies, protein–DNA interactions are routinely detected in the genome scale. Computational methods that detect weak protein-binding signals and simultaneously maintain a high specificity yet remain to be challenging. An attractive approach is to incorporate biologically relevant data, such as protein co-occupancy, to improve the power of protein-binding detection. We call the additional data related with the target protein binding as supporting tracks.

Results: We propose a novel but rigorous statistical method to identify protein occupancy in ChIP data using multiple supporting tracks (PASS2). We demonstrate that utilizing biologically related information can significantly increase the discovery of true protein-binding sites, while still maintaining a desired level of false positive calls. Applying the method to GATA1 restoration in mouse erythroid cell line, we detected many new GATA1-binding sites using GATA1 co-occupancy data.

Availability:  http://stat.psu.edu/∼yuzhang/pass2.tar

Contact:  yuzhang@stat.psu.edu
De-correlating expression in gene-set analysis
Authors: Nam Dougu
Published: September 2010

Motivation: Group-wise pattern analysis of genes, known as gene-set analysis (GSA), addresses the differential expression pattern of biologically pre-defined gene sets. GSA exhibits high statistical power and has revealed many novel biological processes associated with specific phenotypes. In most cases, however, GSA relies on the invalid assumption that the members of each gene set are sampled independently, which increases false predictions.

Results: We propose an algorithm, termed DECO, to remove (or alleviate) the bias caused by the correlation of the expression data in GSAs. This is accomplished through the eigenvalue-decomposition of covariance matrixes and a series of linear transformations of data. In particular, moderate de-correlation methods that truncate or re-scale eigenvalues were proposed for a more reliable analysis. Tests of simulated and real experimental data show that DECO effectively corrects the correlation structure of gene expression and improves the prediction accuracy (specificity and sensitivity) for both gene- and sample-randomizing GSA methods.

Availability: The MATLAB codes and the tested data sets are available at ftp://deco.nims.re.kr/pub or from the author.

Contact:  dougnam@unist.ac.kr
Discovering drug–drug interactions: a text-mining and reasoning approach based on properties of drug metabolism
Authors: Tari Luis , Anwar Saadat , Liang Shanshan , Cai James , Baral Chitta
Published: September 2010

Motivation: Identifying drug–drug interactions (DDIs) is a critical process in drug administration and drug development. Clinical support tools often provide comprehensive lists of DDIs, but they usually lack the supporting scientific evidences and different tools can return inconsistent results. In this article, we propose a novel approach that integrates text mining and automated reasoning to derive DDIs. Through the extraction of various facts of drug metabolism, not only the DDIs that are explicitly mentioned in text can be extracted but also the potential interactions that can be inferred by reasoning.

Results: Our approach was able to find several potential DDIs that are not present in DrugBank. We manually evaluated these interactions based on their supporting evidences, and our analysis revealed that 81.3% of these interactions are determined to be correct. This suggests that our approach can uncover potential DDIs with scientific evidences explaining the mechanism of the interactions.

Contact:  luis.tari@roche.com
Improving disease gene prioritization using the semantic similarity of Gene Ontology terms
Authors: Schlicker Andreas , Lengauer Thomas , Albrecht Mario
Published: September 2010

Motivation: Many hereditary human diseases are polygenic, resulting from sequence alterations in multiple genes. Genomic linkage and association studies are commonly performed for identifying disease-related genes. Such studies often yield lists of up to several hundred candidate genes, which have to be prioritized and validated further. Recent studies discovered that genes involved in phenotypically similar diseases are often functionally related on the molecular level.

Results: Here, we introduce MedSim, a novel approach for ranking candidate genes for a particular disease based on functional comparisons involving the Gene Ontology. MedSim uses functional annotations of known disease genes for assessing the similarity of diseases as well as the disease relevance of candidate genes. We benchmarked our approach with genes known to be involved in 99 diseases taken from the OMIM database. Using artificial quantitative trait loci, MedSim achieved excellent performance with an area under the ROC curve of up to 0.90 and a sensitivity of over 70% at 90% specificity when classifying gene products according to their disease relatedness. This performance is comparable or even superior to related methods in the field, albeit using less and thus more easily accessible information.

Availability: MedSim is offered as part of our FunSimMat web service (http://www.funsimmat.de).

Contact:  mario.albrecht@mpi-inf.mpg.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Efficient parameter search for qualitative models of regulatory networks using symbolic model checking
Authors: Batt Gregory , Page Michel , Cantone Irene , Goessler Gregor , Monteiro Pedro , de Jong Hidde
Published: September 2010

Motivation: Investigating the relation between the structure and behavior of complex biological networks often involves posing the question if the hypothesized structure of a regulatory network is consistent with the observed behavior, or if a proposed structure can generate a desired behavior.

Results: The above questions can be cast into a parameter search problem for qualitative models of regulatory networks. We develop a method based on symbolic model checking that avoids enumerating all possible parametrizations, and show that this method performs well on real biological problems, using the IRMA synthetic network and benchmark datasets. We test the consistency between IRMA and time-series expression profiles, and search for parameter modifications that would make the external control of the system behavior more robust.

Availability: GNA and the IRMA model are available at http://ibis.inrialpes.fr/

Contact:  gregory.batt@inria.fr

Supplementary information:  Supplementary data are available at Bioinformatics online.
A novel approach for determining environment-specific protein costs: the case of Arabidopsis thaliana
Authors: Sajitz-Hermstein Max , Nikoloski Zoran
Published: September 2010

Motivation: Comprehensive understanding of cellular processes requires development of approaches which consider the energetic balances in the cell. The existing approaches that address this problem are based on defining energy-equivalent costs which do not include the effects of a changing environment. By incorporating these effects, one could provide a framework for integrating ‘omics’ data from various levels of the system in order to provide interpretations with respect to the energy state and to elicit conclusions about putative global energy-related response mechanisms in the cell.

Results: Here we define a cost measure for amino acid synthesis based on flux balance analysis of a genome-scale metabolic network, and develop methods for its integration with proteomics and metabolomics data. This is a first measure which accounts for the effect of different environmental conditions. We applied this approach to a genome-scale network of Arabidopsis thaliana and calculated the costs for all amino acids and proteins present in the network under light and dark conditions. Integration of function and process ontology terms in the analysis of protein abundances and their costs indicates that, during the night, the cell favors cheaper proteins compared with the light environment. However, this does not imply that there is squandering of resources during the day. The results from the association analysis between the costs, levels and well-defined expenses of amino acid synthesis, indicate that our approach not only captures the adjustment made at the switch of conditions, but also could explain the anticipation of resource usage via a global energy-related regulatory mechanism of amino acid and protein synthesis.

Contact:  nikoloski@mpimp-golm.mpg.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Inferring cancer subnetwork markers using density-constrained biclustering
Authors: Dao Phuong , Colak Recep , Salari Raheleh , Moser Flavia , Davicioni Elai , Schönhuth Alexander , Ester Martin
Published: September 2010

Motivation: Recent genomic studies have confirmed that cancer is of utmost phenotypical complexity, varying greatly in terms of subtypes and evolutionary stages. When classifying cancer tissue samples, subnetwork marker approaches have proven to be superior over single gene marker approaches, most importantly in cross-platform evaluation schemes. However, prior subnetwork-based approaches do not explicitly address the great phenotypical complexity of cancer.

Results: We explicitly address this and employ density-constrained biclustering to compute subnetwork markers, which reflect pathways being dysregulated in many, but not necessarily all samples under consideration. In breast cancer we achieve substantial improvements over all cross-platform applicable approaches when predicting TP53 mutation status in a well-established non-cross-platform setting. In colon cancer, we raise prediction accuracy in the most difficult instances from 87% to 93% for cancer versus non−cancer and from 83% to (astonishing) 92%, for with versus without liver metastasis, in well-established cross-platform evaluation schemes.

Availability: Software is available on request.

Contact:  alexsch@math.berkeley.edu; ester@cs.sfu.ca

Supplementary information:  Supplementary data are available at Bioinformatics online.
Prediction of a gene regulatory network linked to prostate cancer from gene expression, microRNA and clinical data
Authors: Bonnet Eric , Michoel Tom , Van de Peer Yves
Published: September 2010

Motivation: Cancer is a complex disease, triggered by mutations in multiple genes and pathways. There is a growing interest in the application of systems biology approaches to analyze various types of cancer-related data to understand the overwhelming complexity of changes induced by the disease.

Results: We reconstructed a regulatory module network using gene expression, microRNA expression and a clinical parameter, all measured in lymphoblastoid cell lines derived from patients having aggressive or non-aggressive forms of prostate cancer. Our analysis identified several modules enriched in cell cycle-related genes as well as novel functional categories that might be linked to prostate cancer. Almost one-third of the regulators predicted to control the expression levels of the modules are microRNAs. Several of them have already been characterized as causal in various diseases, including cancer. We also predicted novel microRNAs that have never been associated to this type of tumor. Furthermore, the condition-dependent expression of several modules could be linked to the value of a clinical parameter characterizing the aggressiveness of the prostate cancer. Taken together, our results help to shed light on the consequences of aggressive and non-aggressive forms of prostate cancer.

Availability: The complete regulatory network is available as an interactive supplementary web site at the following URL: http://bioinformatics.psb.ugent.be/webtools/pronet/

Contact:  yves.vandepeer@psb.vib-ugent.be
Mass spectrometry data processing using zero-crossing lines in multi-scale of Gaussian derivative wavelet
Authors: Nguyen Nha , Huang Heng , Oraintara Soontorn , Vo An
Published: September 2010

Motivation: Peaks are the key information in mass spectrometry (MS) which has been increasingly used to discover diseases-related proteomic patterns. Peak detection is an essential step for MS-based proteomic data analysis. Recently, several peak detection algorithms have been proposed. However, in these algorithms, there are three major deficiencies: (i) because the noise is often removed, the true signal could also be removed; (ii) baseline removal step may get rid of true peaks and create new false peaks; (iii) in peak quantification step, a threshold of signal-to-noise ratio (SNR) is usually used to remove false peaks; however, noise estimations in SNR calculation are often inaccurate in either time or wavelet domain. In this article, we propose new algorithms to solve these problems. First, we use bivariate shrinkage estimator in stationary wavelet domain to avoid removing true peaks in denoising step. Second, without baseline removal, zero-crossing lines in multi-scale of derivative Gaussian wavelets are investigated with mixture of Gaussian to estimate discriminative parameters of peaks. Third, in quantification step, the frequency, SD, height and rank of peaks are used to detect both high and small energy peaks with robustness to noise.

Results: We propose a novel Gaussian Derivative Wavelet (GDWavelet) method to more accurately detect true peaks with a lower false discovery rate than existing methods. The proposed GDWavelet method has been performed on the real Surface-Enhanced Laser Desorption/Ionization Time-Of-Flight (SELDI-TOF) spectrum with known polypeptide positions and on two synthetic data with Gaussian and real noise. All experimental results demonstrate that our method outperforms other commonly used methods. The standard receiver operating characteristic (ROC) curves are used to evaluate the experimental results.

Availability:  http://ranger.uta.edu/∼heng/MS/GDWavelet.html or http://www.naaan.org/nhanguyen/archive.htm

Contact:  heng@uta.edu