bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biological network comparison using graphlet degree distribution
Authors: Pržulj Nataša 
Published: January 2007

AbstractMotivation: Analogous to biological sequence comparison, comparing cellular networks is an important problem that could provide insight into biological understanding and therapeutics. For technical reasons, comparing large networks is computationally infeasible, and thus heuristics, such as the degree distribution, clustering coefficient, diameter, and relative graphlet frequency distribution have been sought. It is easy to demonstrate that two networks are different by simply showing a short list of properties in which they differ. It is much harder to show that two networks are similar, as it requires demonstrating their similarity in all of their exponentially many properties. Clearly, it is computationally prohibitive to analyze all network properties, but the larger the number of constraints we impose in determining network similarity, the more likely it is that the networks will truly be similar.Results: We introduce a new systematic measure of a network's local structure that imposes a large number of similarity constraints on networks being compared. In particular, we generalize the degree distribution, which measures the number of nodes ‘touching’ k edges, into distributions measuring the number of nodes ‘touching’ k graphlets, where graphlets are small connected non-isomorphic subgraphs of a large network. Our new measure of network local structure consists of 73 graphlet degree distributions of graphlets with 2–5 nodes, but it is easily extendible to a greater number of constraints (i.e. graphlets), if necessary, and the extensions are limited only by the available CPU. Furthermore, we show a way to combine the 73 graphlet degree distributions into a network ‘agreement’ measure which is a number between 0 and 1, where 1 means that networks have identical distributions and 0 means that they are far apart. Based on this new network agreement measure, we show that almost all of the 14 eukaryotic PPI networks, including human, resulting from various high-throughput experimental techniques, as well as from curated databases, are better modeled by geometric random graphs than by Erdös–Rény, random scale-free, or Barabási–Albert scale-free networks.Availability: Software executables are available upon request.Contact: natasha@ics.uci.edu
Efficient inference on known phylogenetic trees using Poisson regression
Authors: Rosset Saharon 
Published: January 2007

AbstractMotivation: We suggest the use of Poisson regression for time inference and hypothesis testing on a bifurcating Phylogenetic tree with known topology. This method is computationally simple and naturally accommodates variable substitution rates across different sites, without requiring the estimation of these rates. We identify the assumptions under which this is a maximum-likelihood inference approach and show that in some realistic situations—in particular, when the probability of repeated mutation within each branch of the tree is small—these assumptions hold with high probability.Results: Our motivating domain is human mitochondrial DNA trees, and we illustrate our method on a problem of estimating the time to most recent common ancestor of all non-African mtDNA, using publicly available data. We test for molecular clock violations using multiple comparisons, and conclude that the global molecular clock hypothesis cannot be rejected based on these data.Contact: srosset@us.ibm.com
Similarities and differences of gene expression in yeast stress conditions
Authors: Rokhlenko Oleg , Wexler Ydo , Yakhini Zohar 
Published: January 2007

AbstractMotivation and Methods: All living organisms and the survival of all cells critically depend on their ability to sense and quickly adapt to changes in the environment and to other stress conditions. We study stress response mechanisms in Saccharomyces cerevisiae by identifying genes that, according to very stringent criteria, have persistent co-expression under a variety of stress conditions. This is enabled through a fast clique search method applied to the intersection of several co-expression graphs calculated over the data of Gasch et al. This method exploits the topological characteristics of these graphs.Results: We observe cliques in the intersection graphs that are much larger than expected under a null model of changing gene identities for different stress conditions but maintaining the co-expression topology within each one. Persistent cliques are analyzed to identify enriched function as well as enriched regulation by a small number of TFs. These TFs, therefore, characterize a universal and persistent reaction to stress response. We further demonstrate that the vertices (genes) of many cliques in the intersection graphs are co-localized in the yeast genome, to a degree far beyond the random expectation. Co-localization can hypothetically contribute to a quick co-ordinated response. We propose the use of persistent cliques in further study of properties of co-regulation.Supplementary information: Contact: olegro@cs.technion.ac.il
Tandem repeats over the edit distance
Authors: Sokol Dina , Benson Gary , Tojeira Justin 
Published: January 2007

AbstractMotivation: A tandem repeat in DNA is a sequence of two or more contiguous, approximate copies of a pattern of nucleotides. Tandem repeats occur in the genomes of both eukaryotic and prokaryotic organisms. They are important in numerous fields including disease diagnosis, mapping studies, human identity testing (DNA fingerprinting), sequence homology and population studies. Although tandem repeats have been used by biologists for many years, there are few tools available for performing an exhaustive search for all tandem repeats in a given sequence.Results: In this paper we describe an efficient algorithm for finding all tandem repeats within a sequence, under the edit distance measure. The contributions of this paper are two-fold: theoretical and practical. We present a precise definition for tandem repeats over the edit distance and an efficient, deterministic algorithm for finding these repeats.Availability: The algorithm has been implemented in C++, and the software is available upon request and can be used at . The use of this tool will assist biologists in discovering new ways that tandem repeats affect both the structure and function of DNA and protein molecules.Contact: sokol@sci.brooklyn.cuny.edu
Efficient parsimony-based methods for phylogenetic network reconstruction
Authors: Jin Guohua , Nakhleh Luay , Snir Sagi , Tuller Tamir 
Published: January 2007

AbstractMotivation: Phylogenies—the evolutionary histories of groups of organisms—play a major role in representing relationships among biological entities. Although many biological processes can be effectively modeled as tree-like relationships, others, such as hybrid speciation and horizontal gene transfer (HGT), result in networks, rather than trees, of relationships. Hybrid speciation is a significant evolutionary mechanism in plants, fish and other groups of species. HGT plays a major role in bacterial genome diversification and is a significant mechanism by which bacteria develop resistance to antibiotics. Maximum parsimony is one of the most commonly used criteria for phylogenetic tree inference. Roughly speaking, inference based on this criterion seeks the tree that minimizes the amount of evolution. In 1990, Jotun Hein proposed using this criterion for inferring the evolution of sequences subject to recombination. Preliminary results on small synthetic datasets. Nakhleh et al. (2005) demonstrated the criterion’s application to phylogenetic network reconstruction in general and HGT detection in particular. However, the naive algorithms used by the authors are inapplicable to large datasets due to their demanding computational requirements. Further, no rigorous theoretical analysis of computing the criterion was given, nor was it tested on biological data.Results: In the present work we prove that the problem of scoring the parsimony of a phylogenetic network is NP-hard and provide an improved fixed parameter tractable algorithm for it. Further, we devise efficient heuristics for parsimony-based reconstruction of phylogenetic networks. We test our methods on both synthetic and biological data (rbcL gene in bacteria) and obtain very promising results.Contact: ssagi@math.berkeley.edu
Family relationships: should consensus reign?—consensus clustering for protein families
Authors: Nikolski Macha , Sherman David J. 
Published: January 2007

AbstractMotivation: Reliable identification of protein families is key to phylogenetic analysis, functional annotation and the exploration of protein function diversity in a given phylogenetic branch. As more and more complete genomes are sequenced, there is a need for powerful and reliable algorithms facilitating protein families construction.Results: We have formulated the problem of protein families construction as an instance of consensus clustering, for which we designed a novel algorithm that is computationally efficient in practice and produces high quality results. Our algorithm uses an election method to construct consensus families from competing clustering computations.Our consensus clustering algorithm is tailored to serve the specific needs of comparative genomics projects. First, it provides a robust means to incorporate results from different and complementary clustering methods, thus avoiding the need for an a priori choice that may introduce computational bias in the results. Second, it is suited to large-scale projects due to the practical efficiency. And third, it produces high quality results where families tend to represent groupings by biological function.Availability: This method has been used for Génolevures project to compute protein families of Hemiascomycetous yeasts. The data are available online atSupplementary information: Supplementary data are available atContact: macha@labri.fr
A structural alignment kernel for protein structures
Authors: Qiu Jian , Hue Martial , Ben-Hur Asa , Vert Jean-Philippe , Noble William Stafford 
Published: January 2007

AbstractMotivation: This work aims to develop computational methods to annotate protein structures in an automated fashion. We employ a support vector machine (SVM) classifier to map from a given class of structures to their corresponding structural (SCOP) or functional (Gene Ontology) annotation. In particular, we build upon recent work describing various kernels for protein structures, where a kernel is a similarity function that the classifier uses to compare pairs of structures.Results: We describe a kernel that is derived in a straightforward fashion from an existing structural alignment program, MAMMOTH. We find in our benchmark experiments that this kernel significantly out-performs a variety of other kernels, including several previously described kernels. Furthermore, in both benchmarks, classifying structures using MAMMOTH alone does not work as well as using an SVM with the MAMMOTH kernel.Availability: http://noble.gs.washington.edu/proj/3dkernelContact: noble@gs.washington.edu
TreeQ-VISTA: an interactive tree visualization tool with functional annotation query capabilities
Authors: Gu Shengyin , Anderson Iain , Kunin Victor , Cipriano Michael , Minovitsky Simon , Weber Gunther , Amenta Nina , Hamann Bernd , Dubchak Inna 
Published: January 2007

AbstractSummary: We describe a general multiplatform exploratory tool called TreeQ-Vista, designed for presenting functional annotations in a phylogenetic context. Traits, such as phenotypic and genomic properties, are interactively queried from a user-provided relational database with a user-friendly interface which provides a set of tools for users with or without SQL knowledge. The query results are projected onto a phylogenetic tree and can be displayed in multiple color groups. A rich set of browsing, grouping and query tools are provided to facilitate trait exploration, comparison and analysis.Availability: The program, detailed tutorial and examples are available online (http:/genome.lbl.gov/vista/TreeQVista).Contact: vista@lbl.gov
A faster circular binary segmentation algorithm for the analysis of array CGH data
Authors: Venkatraman E. S. , Olshen Adam B. 
Published: January 2007

Abstract
Motivation: Array CGH technologies enable the simultaneous measurement of DNA copy number for thousands of sites on a genome. We developed the circular binary segmentation (CBS) algorithm to divide the genome into regions of equal copy number. The algorithm tests for change-points using a maximal t-statistic with a permutation reference distribution to obtain the corresponding P-value. The number of computations required for the maximal test statistic is O(N2), where N is the number of markers. This makes the full permutation approach computationally prohibitive for the newer arrays that contain tens of thousands markers and highlights the need for a faster algorithm.
Results: We present a hybrid approach to obtain the P-value of the test statistic in linear time. We also introduce a rule for stopping early when there is strong evidence for the presence of a change. We show through simulations that the hybrid approach provides a substantial gain in speed with only a negligible loss in accuracy and that the stopping rule further increases speed. We also present the analyses of array CGH data from breast cancer cell lines to show the impact of the new approaches on the analysis of real data.
Availability: An R version of the CBS algorithm has been implemented in the “DNAcopy” package of the Bioconductor project. The proposed hybrid method for the P-value is available in version 1.2.1 or higher and the stopping rule for declaring a change early is available in version 1.5.1 or higher.
Contact: venkatre@mskcc.org
Supplementary information: Supplementary data are available at Bioinformatics online.
Deleterious SNP prediction: be mindful of your training data!
Authors: Care Matthew A. , Needham Chris J. , Bulpitt Andrew J. , Westhead David R. 
Published: January 2007

AbstractMotivation: To predict which of the vast number of human single nucleotide polymorphisms (SNPs) are deleterious to gene function or likely to be disease associated is an important problem, and many methods have been reported in the literature. All methods require data sets of mutations classified as ‘deleterious’ or ‘neutral’ for training and/or validation. While different workers have used different data sets there has been no study of which is best. Here, the three most commonly used data sets are analysed. We examine their contents and relate this to classifiers, with the aims of revealing the strengths and pitfalls of each data set, and recommending a best approach for future studies.Results: The data sets examined are shown to be substantially different in content, particularly with regard to amino acid substitutions, reflecting the different ways in which they are derived. This leads to differences in classifiers and reveals some serious pitfalls of some data sets, making them less than ideal for non-synonymous SNP prediction.Availability: Software is available on request from the authors.Contact: d.r.westhead@leeds.ac.ukSupplementary information: Supplementary data are available at Bioinformatics online.
Tumor carbonic anhydrase 9 expression is associated with the presence of lymph node metastases in uterine cervical cancer
Authors: Lee Sun , Shin Hye‐Jin , Han In‐Oc , Hong Eun‐Kyung , Park Sang‐Yoon , Roh Ju‐Won , Shin Kyung H. , Kim Tae H. , Kim Joo‐Young 
Published: January 2007

Tumor hypoxia has a pronounced effect on malignant progression and metastatic spread of human tumors. As carbonic anhydrases (CA) 9 and 12 are induced by the low‐oxygen environment within tumors, we investigated the relationship between the expression of these two CA and the presence of metastatic lymph nodes (LN) in uterine cervical cancer. CA9/CA12 expression was evaluated histochemically in primary cervical cancer tissues of 73 patients who underwent laparoscopic LN staging and two patients with clinical staging before definitive radiotherapy at the National Cancer Center, Korea. We also evaluated CA9 expression in 33 patients with pathologically confirmed metastatic LN. CA9 expression in the primary tumors was significantly associated with LN metastasis (P = 0.03) and poorer disease‐free survival (relative risk, 6.1; 95% confidence interval, 1.3–28.3, P = 0.02, multivariate analysis), whereas CA12 expression did not show such a relationship. In addition, 21 of 24 metastatic LN revealed similar CA9 expression (P = 0.001), suggesting that CA9‐expressing tumor cells had a higher metastatic potential. CA9 was expressed in 45 of 75 (60%) primary tumors, with positive tumor cells observed predominantly in the area away from the blood vessels. In contrast, CA12 expression was observed in only 29 of 74 primary tumors (39%), without a specific pattern. These findings indicate that expression of CA9, but not CA12, in tumors is associated with the presence of LN metastases and poorer prognosis. Selective application of new treatment modalities based on CA9 expression to prevent LN metastases may improve overall treatment outcome in patients with uterine cervical cancer. (Cancer Sci 2007; 98: 329–333)
Assessment of potential ecological disruption based on heavy metal toxicity, accumulation and distribution in media of the Lagos Lagoon
Authors: Adebayo Otitoloju A. , Kio Don‐Pedro N. , Emmanuel Oyewo O. 
Published: January 2007

AbstractToxicity evaluations of heavy metals against three benthic animals, Tympanotonus fuscatus, Clibanarius africanus and Sesarma huzardi of the Lagos Lagoon were carried out under laboratory conditions. On the basis of the 96hLC50 values, Cd was found to be the most toxic metal tested followed by Cu, Zn and Pb, in a descending order of toxicity against T. fuscatus and S. huzardi; however, against C. africanus, Cu was the most toxic followed by Cd, Zn and Pb (least toxic). The determination of the metal concentrations in the water column and sediment of the Lagos Lagoon revealed that these media of the lagoon contained measurable concentrations of heavy metals but the levels were still several folds lower than the concentrations that will cause 50% mortality of exposed animals under laboratory conditions. The significance of the observed differences between the 96hLC50 values of the test metals, the concentration of heavy metals detected in tissues of field animals and ambient levels of the metals in the Lagos lagoon were discussed in relation to the protection of aquatic lives and potential public health risks. The need to verify the possibilities of synergistic interactions between the constituent metals when acting jointly against the exposed animals was recommended.
Maternal concerns during early parenthood
Authors: Kaitz M. 
Published: January 2007

AbstractBackground  Most research on maternal concerns has focused on their assessment during pregnancy and the early post‐partum period. The aim of this study was to identify primary concerns of mothers later in the first post‐partum year, changes over time, and factors that were associated with relatively intense concerns, including infant (difficult) temperament, hours employed out of the home and obstetrical complications during pregnancy or childbirth.Method  Data were obtained from 366 first‐time (Israeli) mothers at 3 and 6 months post‐partum by employing a new tool, the Mothers' Concern Questionnaire, along with standardized questionnaires, administered by phone.Results  Analyses revealed six dimensions of concerns (Family Health, Return to Work, Mother's Well‐being, Relationships/Support, Infant Care, and Spouse). Of these, issues related to returning to work and family health were of most concern, and ratings were higher at 3 months than at 6 months post‐partum. Women with higher‐than‐average total concern scores perceived their infant as more difficult, were more likely to have experienced an obstetric complication, and worked more hours out of the house than women with lower‐than‐average scores.Conclusions  The findings afford a first look at the profile of normative maternal concerns outside of the immediate post‐partum period and identify factors that predict more intense concerns. These findings extend what we know about the issues of new mothers and can guide birth educators and help couples prepare themselves for parenthood.
Peroxisome proliferator‐activated receptor‐γ agonists inhibit respiratory syncytial virus‐induced expression of intercellular adhesion molecule‐1 in human lung epithelial cells
Authors: Arnold Ralf , Neumann Manfred , König Wolfgang 
Published: January 2007

SummaryRespiratory syncytial virus (RSV) is the major causative agent of severe lower respiratory tract disease and death in infants worldwide. The epithelial cells of the airways are the target cells for RSV infection and the site of the majority of the inflammation associated with the disease. However, despite five decades of intensive RSV research there exist neither an effective active vaccine nor a promising antiviral and anti‐inflammatory therapy. Recently, peroxisome proliferator‐activated receptor‐γ (PPAR‐γ), a member of the nuclear hormone receptor superfamily, has been shown to possess anti‐inflammatory properties. Therefore, we hypothesized whether the detrimental increase of intercellular adhesion molecule‐1 (ICAM‐1) on RSV‐infected lung epithelial cells (A549 and primary normal human bronchial epithelial cells (NHBE)) might be modulated by natural and synthetic PPAR‐γ agonists (15d‐PGJ2, ciglitazone, troglitazone, Fmoc‐Leu). Our data show that all PPAR‐γ agonists under study significantly down‐regulated the RSV‐induced expression of ICAM‐1 on A549‐ and NHBE cells in a dose‐dependent manner resulting in a reduced β2 integrin‐mediated adhesion of monocytic effector cells (U937) to RSV‐infected A549 cell monolayers. In contrast, the PPAR‐α agonist bezafibrate had no impact on the RSV‐induced ICAM‐1 expression. The reduced ICAM‐1 expression was associated with a diminished ICAM‐1 mRNA level and binding activity of nuclear factor‐κB (p65/p50) in A549 cells. These findings suggest that PPARγ agonists have beneficial effects in the suppression of the inflammatory response during RSV infection and therefore might have clinical efficacy in the course of severe RSV‐infection.
Bone morphogenetic protein‐2/4 signalling pathway components are expressed in the human thymus and inhibit early T‐cell development
Authors: Cejalvo Teresa , Sacedón Rosa , Hernández‐López Carmen , Diez Blanca , Gutierrez‐Frías Cruz , Valencia Jaris , Zapata Agustín G. , Varas Alberto , Vicente Angeles 
Published: January 2007

SummaryT‐cell differentiation is driven by a complex network of signals mainly derived from the thymic epithelium. In this study we demonstrate in the human thymus that cortical epithelial cells produce bone morphogenetic protein 2 (BMP2) and BMP4 and that both thymocytes and thymic epithelium express all the molecular machinery required for a response to these proteins. BMP receptors, BMPRIA and BMPRII, are mainly expressed by cortical thymocytes while BMPRIB is expressed in the majority of the human thymocytes. Some thymic epithelial cells from cortical and medullary areas express BMP receptors, being also cell targets for in vivo BMP2/4 signalling. The treatment with BMP4 of chimeric human–mouse fetal thymic organ cultures seeded with CD34+ human thymic progenitors results in reduced cell recovery and inhibition of the differentiation of human thymocytes from CD4− CD8− to CD4+ CD8+ cell stages. These results support a role for BMP2/4 signalling in human T‐cell differentiation.