bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reconstruction of the neuromuscular junction connectome
Authors: Srinivasan Ranga , Li Qing , Zhou Xiaobo , Lu Ju , Lichtman Jeff , Wong Stephen T.C. 
Published: June 2010

Abstract
Motivation: Unraveling the structure and behavior of the brain and central nervous system (CNS) has always been a major goal of neuroscience. Understanding the wiring diagrams of the neuromuscular junction connectomes (full connectivity of nervous system neuronal components) is a starting point for this, as it helps in the study of the organizational and developmental properties of the mammalian CNS. The phenomenon of synapse elimination during developmental stages of the neuronal circuitry is such an example. Due to the organizational specificity of the axons in the connectomes, it becomes important to label and extract individual axons for morphological analysis. Features such as axonal trajectories, their branching patterns, geometric information, the spatial relations of groups of axons, etc. are of great interests for neurobiologists in the study of wiring diagrams. However, due to the complexity of spatial structure of the axons, automatically tracking and reconstructing them from microscopy images in 3D is an unresolved problem. In this article, AxonTracker-3D, an interactive 3D axon tracking and labeling tool is built to obtain quantitative information by reconstruction of the axonal structures in the entire innervation field. The ease of use along with accuracy of results makes AxonTracker-3D an attractive tool to obtain valuable quantitative information from axon datasets.
Availability: The software is freely available for download at http://www.cbi-tmhs.org/AxonTracker/
Contact: stwong@tmhs.org
VARiD: A variation detection framework for color-space and letter-space platforms
Authors: Dalca Adrian V. , Rumble Stephen M. , Levy Samuel , Brudno Michael 
Published: June 2010

Abstract
Motivation: High-throughput sequencing (HTS) technologies are transforming the study of genomic variation. The various HTS technologies have different sequencing biases and error rates, and while most HTS technologies sequence the residues of the genome directly, generating base calls for each position, the Applied Biosystem's SOLiD platform generates dibase-coded (color space) sequences. While combining data from the various platforms should increase the accuracy of variation detection, to date there are only a few tools that can identify variants from color space data, and none that can analyze color space and regular (letter space) data together.
Results: We present VARiD—a probabilistic method for variation detection from both letter- and color-space reads simultaneously. VARiD is based on a hidden Markov model and uses the forward-backward algorithm to accurately identify heterozygous, homozygous and tri-allelic SNPs, as well as micro-indels. Our analysis shows that VARiD performs better than the AB SOLiD toolset at detecting variants from color-space data alone, and improves the calls dramatically when letter- and color-space reads are combined.
Availability: The toolset is freely available at http://compbio.cs.utoronto.ca/varid
Contact: varid@cs.toronto.edu
TEAM: efficient two-locus epistasis tests in human genome-wide association study
Authors: Zhang Xiang , Huang Shunping , Zou Fei , Wang Wei 
Published: June 2010

Abstract
As a promising tool for identifying genetic markers underlying phenotypic differences, genome-wide association study (GWAS) has been extensively investigated in recent years. In GWAS, detecting epistasis (or gene–gene interaction) is preferable over single locus study since many diseases are known to be complex traits. A brute force search is infeasible for epistasis detection in the genome-wide scale because of the intensive computational burden. Existing epistasis detection algorithms are designed for dataset consisting of homozygous markers and small sample size. In human study, however, the genotype may be heterozygous, and number of individuals can be up to thousands. Thus, existing methods are not readily applicable to human datasets. In this article, we propose an efficient algorithm, TEAM, which significantly speeds up epistasis detection for human GWAS. Our algorithm is exhaustive, i.e. it does not ignore any epistatic interaction. Utilizing the minimum spanning tree structure, the algorithm incrementally updates the contingency tables for epistatic tests without scanning all individuals. Our algorithm has broader applicability and is more efficient than existing methods for large sample study. It supports any statistical test that is based on contingency tables, and enables both family-wise error rate and false discovery rate controlling. Extensive experiments show that our algorithm only needs to examine a small portion of the individuals to update the contingency tables, and it achieves at least an order of magnitude speed up over the brute force approach.
Contact: xiang@cs.unc.edu
SuperTriplets: a triplet-based supertree approach to phylogenomics
Authors: Ranwez Vincent , Criscuolo Alexis , Douzery Emmanuel J.P. 
Published: June 2010

AbstractMotivation: Phylogenetic tree-building methods use molecular data to represent the evolutionary history of genes and taxa. A recurrent problem is to reconcile the various phylogenies built from different genomic sequences into a single one. This task is generally conducted by a two-step approach whereby a binary representation of the initial trees is first inferred and then a maximum parsimony (MP) analysis is performed on it. This binary representation uses a decomposition of all source trees that is usually based on clades, but that can also be based on triplets or quartets. The relative performances of these representations have been discussed but are difficult to assess since both are limited to relatively small datasets.Results: This article focuses on the triplet-based representation of source trees. We first recall how, using this representation, the parsimony analysis is related to the median tree notion. We then introduce SuperTriplets, a new algorithm that is specially designed to optimize this alternative formulation of the MP criterion. The method avoids several practical limitations of the triplet-based binary matrix representation, making it useful to deal with large datasets. When the correct resolution of every triplet appears more often than the incorrect ones in source trees, SuperTriplets warrants to reconstruct the correct phylogeny. Both simulations and a case study on mammalian phylogenomics confirm the advantages of this approach. In both cases, SuperTriplets tends to propose less resolved but more reliable supertrees than those inferred using Matrix Representation with Parsimony.Availability: Online and JAVA standalone versions of SuperTriplets are available at http://www.supertriplets.univ-montp2.fr/Contact: vincent.ranwez@univ-montp2.fr
Assessing the functional coherence of gene sets with metrics based on the Gene Ontology graph
Authors: Richards Adam J. , Muller Brian , Shotwell Matthew , Cowart L. Ashley , Rohrer Bäerbel , Lu Xinghua 
Published: June 2010

AbstractMotivation: The results of initial analyses for many high-throughput technologies commonly take the form of gene or protein sets, and one of the ensuing tasks is to evaluate the functional coherence of these sets. The study of gene set function most commonly makes use of controlled vocabulary in the form of ontology annotations. For a given gene set, the statistical significance of observing these annotations or ‘enrichment’ may be tested using a number of methods. Instead of testing for significance of individual terms, this study is concerned with the task of assessing the global functional coherence of gene sets, for which novel metrics and statistical methods have been devised.Results: The metrics of this study are based on the topological properties of graphs comprised of genes and their Gene Ontology annotations. A novel aspect of these methods is that both the enrichment of annotations and the relationships among annotations are considered when determining the significance of functional coherence. We applied our methods to perform analyses on an existing database and on microarray experimental results. Here, we demonstrated that our approach is highly discriminative in terms of differentiating coherent gene sets from random ones and that it provides biologically sensible evaluations in microarray analysis. We further used examples to show the utility of graph visualization as a tool for studying the functional coherence of gene sets.Availability: The implementation is provided as a freely accessible web application at: http://projects.dbbe.musc.edu/gosteiner. Additionally, the source code written in the Python programming language, is available under the General Public License of the Free Software Foundation.Contact: lux@musc.eduSupplementary information: Supplementary data are available at Bioinformatics online.
Robust unmixing of tumor states in array comparative genomic hybridization data
Authors: Tolliver David , Tsourakakis Charalampos , Subramanian Ayshwarya , Shackney Stanley , Schwartz Russell 
Published: June 2010

Abstract
Motivation: Tumorigenesis is an evolutionary process by which tumor cells acquire sequences of mutations leading to increased growth, invasiveness and eventually metastasis. It is hoped that by identifying the common patterns of mutations underlying major cancer sub-types, we can better understand the molecular basis of tumor development and identify new diagnostics and therapeutic targets. This goal has motivated several attempts to apply evolutionary tree reconstruction methods to assays of tumor state. Inference of tumor evolution is in principle aided by the fact that tumors are heterogeneous, retaining remnant populations of different stages along their development along with contaminating healthy cell populations. In practice, though, this heterogeneity complicates interpretation of tumor data because distinct cell types are conflated by common methods for assaying the tumor state. We previously proposed a method to computationally infer cell populations from measures of tumor-wide gene expression through a geometric interpretation of mixture type separation, but this approach deals poorly with noisy and outlier data.
Results: In the present work, we propose a new method to perform tumor mixture separation efficiently and robustly to an experimental error. The method builds on the prior geometric approach but uses a novel objective function allowing for robust fits that greatly reduces the sensitivity to noise and outliers. We further develop an efficient gradient optimization method to optimize this ‘soft geometric unmixing’ objective for measurements of tumor DNA copy numbers assessed by array comparative genomic hybridization (aCGH) data. We show, on a combination of semi-synthetic and real data, that the method yields fast and accurate separation of tumor states.
Conclusions: We have shown a novel objective function and optimization method for the robust separation of tumor sub-types from aCGH data and have shown that the method provides fast, accurate reconstruction of tumor states from mixed samples. Better solutions to this problem can be expected to improve our ability to accurately identify genetic abnormalities in primary tumor samples and to infer patterns of tumor evolution.
Contact: tolliver@cs.cmu.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Optimal algorithms for haplotype assembly from whole-genome sequence data
Authors: He Dan , Choi Arthur , Pipatsrisawat Knot , Darwiche Adnan , Eskin Eleazar 
Published: June 2010

Abstract
Motivation: Haplotype inference is an important step for many types of analyses of genetic variation in the human genome. Traditional approaches for obtaining haplotypes involve collecting genotype information from a population of individuals and then applying a haplotype inference algorithm. The development of high-throughput sequencing technologies allows for an alternative strategy to obtain haplotypes by combining sequence fragments. The problem of ‘haplotype assembly’ is the problem of assembling the two haplotypes for a chromosome given the collection of such fragments, or reads, and their locations in the haplotypes, which are pre-determined by mapping the reads to a reference genome. Errors in reads significantly increase the difficulty of the problem and it has been shown that the problem is NP-hard even for reads of length 2. Existing greedy and stochastic algorithms are not guaranteed to find the optimal solutions for the haplotype assembly problem.
Results: In this article, we proposed a dynamic programming algorithm that is able to assemble the haplotypes optimally with time complexity O(m × 2k × n), where m is the number of reads, k is the length of the longest read and n is the total number of SNPs in the haplotypes. We also reduce the haplotype assembly problem into the maximum satisfiability problem that can often be solved optimally even when k is large. Taking advantage of the efficiency of our algorithm, we perform simulation experiments demonstrating that the assembly of haplotypes using reads of length typical of the current sequencing technologies is not practical. However, we demonstrate that the combination of this approach and the traditional haplotype phasing approaches allow us to practically construct haplotypes containing both common and rare variants.
Contact: danhe@cs.ucla.edu
Thermodynamics of RNA structures by Wang–Landau sampling
Authors: Lou Feng , Clote Peter 
Published: June 2010

Abstract
Motivation: Thermodynamics-based dynamic programming RNA secondary structure algorithms have been of immense importance in molecular biology, where applications range from the detection of novel selenoproteins using expressed sequence tag (EST) data, to the determination of microRNA genes and their targets. Dynamic programming algorithms have been developed to compute the minimum free energy secondary structure and partition function of a given RNA sequence, the minimum free-energy and partition function for the hybridization of two RNA molecules, etc. However, the applicability of dynamic programming methods depends on disallowing certain types of interactions (pseudoknots, zig-zags, etc.), as their inclusion renders structure prediction an nondeterministic polynomial time (NP)-complete problem. Nevertheless, such interactions have been observed in X-ray structures.
Results: A non-Boltzmannian Monte Carlo algorithm was designed by Wang and Landau to estimate the density of states for complex systems, such as the Ising model, that exhibit a phase transition. In this article, we apply the Wang-Landau (WL) method to compute the density of states for secondary structures of a given RNA sequence, and for hybridizations of two RNA sequences. Our method is shown to be much faster than existent software, such as RNAsubopt. From density of states, we compute the partition function over all secondary structures and over all pseudoknot-free hybridizations. The advantage of the WL method is that by adding a function to evaluate the free energy of arbitary pseudoknotted structures and of arbitrary hybridizations, we can estimate thermodynamic parameters for situations known to be NP-complete. This extension to pseudoknots will be made in the sequel to this article; in contrast, the current article describes the WL algorithm applied to pseudoknot-free secondary structures and hybridizations.
Availability: The WL RNA hybridization web server is under construction at http://bioinformatics.bc.edu/clotelab/.
Contact: clote@bc.edu
PathText: a text mining integrator for biological pathway visualizations
Authors: Kemper Brian , Matsuzaki Takuya , Matsuoka Yukiko , Tsuruoka Yoshimasa , Kitano Hiroaki , Ananiadou Sophia , Tsujii Jun'ichi 
Published: June 2010

Abstract
Motivation: Metabolic and signaling pathways are an increasingly important part of organizing knowledge in systems biology. They serve to integrate collective interpretations of facts scattered throughout literature. Biologists construct a pathway by reading a large number of articles and interpreting them as a consistent network, but most of the models constructed currently lack direct links to those articles. Biologists who want to check the original articles have to spend substantial amounts of time to collect relevant articles and identify the sections relevant to the pathway. Furthermore, with the scientific literature expanding by several thousand papers per week, keeping a model relevant requires a continuous curation effort. In this article, we present a system designed to integrate a pathway visualizer, text mining systems and annotation tools into a seamless environment. This will enable biologists to freely move between parts of a pathway and relevant sections of articles, as well as identify relevant papers from large text bases. The system, PathText, is developed by Systems Biology Institute, Okinawa Institute of Science and Technology, National Centre for Text Mining (University of Manchester) and the University of Tokyo, and is being used by groups of biologists from these locations.
Contact: brian@monrovian.com.
Galectin‐3, cardiac structure and function, and long‐term mortality in patients with acutely decompensated heart failure
Authors: Shah Ravi V. , Chen‐Tournoux Annabel A. , Picard Michael H. , van Kimmenade Roland R. J. , Januzzi James L. 
Published: June 2010

AimsTo determine the relationship between galectin‐3 concentrations and cardiac structure in patients with acute dyspnoea, and to evaluate the impact of galectin‐3 independent of echocardiographic measurements on long‐term mortality.Methods and resultsOne hundred and fifteen patients presenting to the emergency department with acute dyspnoea who had galectin‐3 levels and detailed echocardiographic studies on admission were studied. Galectin‐3 levels were associated with older age (r = 0.26, P = 0.006), lower creatinine clearance (r = −0.42, P < 0.001), and higher levels of N‐terminal‐proBNP (r = 0.39, P < 0.001). Higher galectin‐3 levels were associated with tissue Doppler E/Ea ratio (r = 0.35, P = 0.01), a lower right ventricular (RV) fractional area change (r = −0.19, P = 0.05), higher RV systolic pressure (r = 0.37, P < 0.001), and more severe mitral (r = 0.30, P = 0.001) or tricuspid regurgitation (r = 0.26, P = 0.005). In patients diagnosed with heart failure (HF), the association between galectin‐3 and valvular regurgitation and RV systolic pressure persisted. In a multivariate Cox regression model, galectin‐3 remained a significant predictor of 4‐year mortality independent of echocardiographic markers of risk. Dyspnoeic patients with HF and galectin‐3 levels above the median value had a 63% mortality; patients less than the median value had a 37% mortality (P = 0.003).ConclusionAmong dyspnoeic patients with and without ADHF, galectin‐3 concentrations are associated with echocardiographic markers of ventricular function. In patients with ADHF, a single admission galectin‐3 level predicts mortality to 4 years, independent of echocardiographic markers of disease severity.
Impact of erythropoiesis‐stimulating agents on morbidity and mortality in patients with heart failure: an updated, post‐TREAT meta‐analysis
Authors: Desai Akshay , Lewis Eldrin , Solomon Scott , McMurray John J.V. , Pfeffer Marc 
Published: June 2010

AimsRandomized clinical trials have suggested that treatment of anaemia with erythropoiesis‐stimulating agents (ESAs) in patients with cancer or chronic kidney disease may increase cardiovascular risk. We therefore examined the effect of treating anaemia with an ESA in patients with heart failure in a meta‐analysis of randomized clinical trials, including the recently reported TREAT study.Methods and resultsWe performed a systematic review and meta‐analysis of all prospective, randomized, controlled studies of ESAs enrolling patients with heart failure and reporting data on mortality or non‐fatal heart failure events. Of 10 trials initially identified by our search strategy, we pooled data from 9 placebo‐controlled studies enrolling a total of 2039 patients, of whom 1023 (50.2%) were allocated to ESA treatment. The pooled risk ratio for ESA treatment relative to placebo was 1.03 [95% confidence interval (CI): 0.89–1.21, P = 0.68] for overall mortality and 0.95 (95% CI: 0.82–1.10, P = 0.46) for worsening heart failure.ConclusionsThe use of ESAs to manage anaemia in patients with heart failure was associated with a neutral effect on both mortality and non‐fatal heart failure events. Definitive assessment of the balance of risk and benefit in this population awaits the completion of a randomized clinical trial adequately powered to assess clinical outcomes.
First Report of Leaf Spot Caused by Bipolaris setariae on Cassava in China
Authors: Shi T. , Li C.-P. , Li J.-F. , Cai J.-M. , Huang G.-X. 
Published: June 2010

Cassava (Manihot esculenta Crantz) is an important food crop in tropical regions of China. Seventy percent of the cassava output is used for starch and ethanol production and it has become the base of food and bioenergy industries. In July 2009, a new leaf spot disease was found on cv. HuaNan205 from a cassava plantation in Danzhou, Hainan Province. Disease occurred on 50% or less of the plants. Initial symptoms were elliptical, chlorotic, and water-immersion lesions of 2 to 4 mm in diameter. These lesions became dry and yellow due to the progress of the disease. A brown halo was around the lesions, and in wet conditions, a dark gray mildew often appeared in the middle of the lesion. Diseased leaves turned yellow and the plants eventually became defoliated. The pathogen was isolated and pathogenicity was established by following Koch's postulates. Young, healthy, and fully expanded green leaves of Cassava cv. HuaNan205 were surface sterilized and then inoculated by spraying them with a suspension of conidia (1 × 105 conidia per ml) of the isolate. Sterile water was used as a control. The leaves were kept in a humid chamber at 28°C for 4 days, at which time similar symptoms to those described above were observed on the leaves. The pathogen was reisolated from inoculated leaves. Microscopic examination showed the conidiophores were fasciculate and brown, septate and straight, and the basal cell was enlarged and hemispherical. Well-developed conidia were long-obclavate, obtuse at both ends, straight, brown, with five to eight transverse septa, and measured 49.7 to 117.1 × 13.3 to 17.2 μm. Genomic DNA of this isolate was extracted with a cetyltrimethylammoniumbromide protocol, and amplification and sequencing of the internal transcribed spacer (ITS) region of rDNA was performed with procedures outlined by Cooke et al. (2). The sequence of the region was deposited in GenBank (Accession No. GU290228). Comparison of the sequences available in the GenBank database revealed that the current ITS sequence differs by three base pairs from two Bipolaris setariae isolates (EF452444 and FJ606786). Morphological identification and sequence analysis of ITS rDNA showed that the pathogen was B. setariae. B. setariae is one of the most important pathogens of lawn grass, gramineous crops, and other plants (1,3). However, no leaf spot disease caused by B. setariae has been recorded previously on cassava in China or elsewhere. References: (1) P. Busey. Crop Sci. 43:1899, 2003. (2) D. E. L. Cooke et al. Fungal Genet. Biol. 30:17, 2000. (3) H. D. Wells and W. W. Hanna. Phytopathology 78:1179, 1988.