bluuebunny/crossref_metadata_2025_split huggingface dataset:
MOTIF-EM: an automated computational tool for identifying conserved regions in CryoEM structures
Authors: Saha Mitul , Levitt Michael , Chiu Wah 
Published: June 2010

Abstract
We present a new, first-of-its-kind, fully automated computational tool MOTIF-EM for identifying regions or domains or motifs in cryoEM maps of large macromolecular assemblies (such as chaperonins, viruses, etc.) that remain conformationally conserved. As a by-product, regions in structures that are not conserved are revealed: this can indicate local molecular flexibility related to biological activity. MOTIF-EM takes cryoEM volumetric maps as inputs. The technique used by MOTIF-EM to detect conserved sub-structures is inspired by a recent breakthrough in 2D object recognition. The technique works by constructing rotationally invariant, low-dimensional representations of local regions in the input cryoEM maps. Correspondences are established between the reduced representations (by comparing them using a simple metric) across the input maps. The correspondences are clustered using hash tables and graph theory is used to retrieve conserved structural domains or motifs. MOTIF-EM has been used to extract conserved domains occurring in large macromolecular assembly maps, including as those of viruses P22 and epsilon 15, Ribosome 70S, GroEL, that remain structurally conserved in different functional states. Our method can also been used to build atomic models for some maps. We also used MOTIF-EM to identify the conserved folds shared among dsDNA bacteriophages HK97, Epsilon 15, and ô29, though they have low-sequence similarity.
Contact: mitul@cs.stanford.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Recognition of beta-structural motifs using hidden Markov models trained with simulated evolution
Authors: Kumar Anoop , Cowen Lenore 
Published: June 2010

Abstract
Motivation: One of the most successful methods to date for recognizing protein sequences that are evolutionarily related, has been profile hidden Markov models. However, these models do not capture pairwise statistical preferences of residues that are hydrogen bonded in β-sheets. We thus explore methods for incorporating pairwise dependencies into these models.
Results: We consider the remote homology detection problem for β-structural motifs. In particular, we ask if a statistical model trained on members of only one family in a SCOP β-structural superfamily, can recognize members of other families in that superfamily. We show that HMMs trained with our pairwise model of simulated evolution achieve nearly a median 5% improvement in AUC for β-structural motif recognition as compared to ordinary HMMs.
Availability: All datasets and HMMs are available at: http://bcb.cs.tufts.edu/pairwise/
Contact: anoop.kumar@tufts.edu; lenore.cowen@tufts.edu
Model-based detection of alternative splicing signals
Authors: Barash Yoseph , Blencowe Benjamin J. , Frey Brendan J. 
Published: June 2010

Abstract
Motivation: Transcripts from ∼95% of human multi-exon genes are subject to alternative splicing (AS). The growing interest in AS is propelled by its prominent contribution to transcriptome and proteome complexity and the role of aberrant AS in numerous diseases. Recent technological advances enable thousands of exons to be simultaneously profiled across diverse cell types and cellular conditions, but require accurate identification of condition-specific splicing changes. It is necessary to accurately identify such splicing changes to elucidate the underlying regulatory programs or link the splicing changes to specific diseases.
Results: We present a probabilistic model tailored for high-throughput AS data, where observed isoform levels are explained as combinations of condition-specific AS signals. According to our formulation, given an AS dataset our tasks are to detect common signals in the data and identify the exons relevant to each signal. Our model can incorporate prior knowledge about underlying AS signals, measurement quality and gene expression level effects. Using a large-scale multi-tissue AS dataset, we demonstrate the advantage of our method over standard alternative approaches. In addition, we describe newly found tissue-specific AS signals which were verified experimentally, and discuss associated regulatory features.
Contact: yoseph@psi.utoronto.ca; frey@psi.utoronto.ca
Supplementary information: Supplementary data are available at Bioinformatics online.
A fast mathematical programming procedure for simultaneous fitting of assembly components into cryoEM density maps
Authors: Zhang Shihua , Vasishtan Daven , Xu Min , Topf Maya , Alber Frank 
Published: June 2010

Abstract
Motivation: Single-particle cryo electron microscopy (cryoEM) typically produces density maps of macromolecular assemblies at intermediate to low resolution (∼5–30 Å). By fitting high-resolution structures of assembly components into these maps, pseudo-atomic models can be obtained. Optimizing the quality-of-fit of all components simultaneously is challenging due to the large search space that makes the exhaustive search over all possible component configurations computationally unfeasible.
Results: We developed an efficient mathematical programming algorithm that simultaneously fits all component structures into an assembly density map. The fitting is formulated as a point set matching problem involving several point sets that represent component and assembly densities at a reduced complexity level. In contrast to other point matching algorithms, our algorithm is able to match multiple point sets simultaneously and not only based on their geometrical equivalence, but also based on the similarity of the density in the immediate point neighborhood. In addition, we present an efficient refinement method based on the Iterative Closest Point registration algorithm. The integer quadratic programming method generates an assembly configuration in a few seconds. This efficiency allows the generation of an ensemble of candidate solutions that can be assessed by an independent scoring function. We benchmarked the method using simulated density maps of 11 protein assemblies at 20 Å, and an experimental cryoEM map at 23.5 Å resolution. Our method was able to generate assembly structures with root-mean-square errors &lt;6.5 Å, which have been further reduced to &lt;1.8 Å by the local refinement procedure.
Availability: The program is available upon request as a Matlab code package.
Contact: alber@usc.edu and m.topf@cryst.bbk.ac.uk
Supplementary information: Supplementary data are available at Bioinformatics Online.
Estimating genome-wide IBD sharing from SNP data via an efficient hidden Markov model of LD with application to gene mapping
Authors: Bercovici Sivan , Meek Christopher , Wexler Ydo , Geiger Dan 
Published: June 2010

AbstractMotivation: Association analysis is the method of choice for studying complex multifactorial diseases. The premise of this method is that affected persons contain some common genomic regions with similar SNP alleles and such areas will be found in this analysis. An important disadvantage of GWA studies is that it does not distinguish between genomic areas that are inherited from a common ancestor [identical by descent (IBD)] and areas that are identical merely by state [identical by state (IBS)]. Clearly, areas that can be marked with higher probability as IBD and have the same correlation with the disease status of identical areas that are more probably only IBS, are better candidates to be causative, and yet this distinction is not encoded in standard association analysis.Results: We develop a factorial hidden Markov model-based algorithm for computing genome-wide IBD sharing. The algorithm accepts as input SNP data of measured individuals and estimates the probability of IBD at each locus for every pair of individuals. For two g-degree relatives, when g≥8, the computation yields a precision of IBD tagging of over 50% higher than previous methods for 95% recall. Our algorithm uses a first-order Markovian model for the linkage disequilibrium process and employs a reduction of the state space of the inheritance vector from being exponential in g to quadratic. The higher accuracy along with the reduced time complexity marks our method as a feasible means for IBD mapping in practical scenarios.Availability: A software implementation, called IBDMAP, is freely available at http://bioinfo.cs.technion.ac.il/IBDmap.Contact: sberco@gmail.com
Discovering transcriptional modules by Bayesian data integration
Authors: Savage Richard S. , Ghahramani Zoubin , Griffin Jim E. , de la Cruz Bernard J. , Wild David L. 
Published: June 2010

AbstractMotivation: We present a method for directly inferring transcriptional modules (TMs) by integrating gene expression and transcription factor binding (ChIP-chip) data. Our model extends a hierarchical Dirichlet process mixture model to allow data fusion on a gene-by-gene basis. This encodes the intuition that co-expression and co-regulation are not necessarily equivalent and hence we do not expect all genes to group similarly in both datasets. In particular, it allows us to identify the subset of genes that share the same structure of transcriptional modules in both datasets.Results: We find that by working on a gene-by-gene basis, our model is able to extract clusters with greater functional coherence than existing methods. By combining gene expression and transcription factor binding (ChIP-chip) data in this way, we are better able to determine the groups of genes that are most likely to represent underlying TMs.Availability: If interested in the code for the work presented in this article, please contact the authors.Contact: d.l.wild@warwick.ac.ukSupplementary information: Supplementary data are available at Bioinformatics online.
Inferring combinatorial association logic networks in multimodal genome-wide screens
Authors: de Ridder Jeroen , Gerrits Alice , Bot Jan , de Haan Gerald , Reinders Marcel , Wessels Lodewyk 
Published: June 2010

Abstract
Motivation: We propose an efficient method to infer combinatorial association logic networks from multiple genome-wide measurements from the same sample. We demonstrate our method on a genetical genomics dataset, in which we search for Boolean combinations of multiple genetic loci that associate with transcript levels.
Results: Our method provably finds the global solution and is very efficient with runtimes of up to four orders of magnitude faster than the exhaustive search. This enables permutation procedures for determining accurate false positive rates and allows selection of the most parsimonious model. When applied to transcript levels measured in myeloid cells from 24 genotyped recombinant inbred mouse strains, we discovered that nine gene clusters are putatively modulated by a logical combination of trait loci rather than a single locus. A literature survey supports and further elucidates one of these findings. Due to our approach, optimal solutions for multi-locus logic models and accurate estimates of the associated false discovery rates become feasible. Our algorithm, therefore, offers a valuable alternative to approaches employing complex, albeit suboptimal optimization strategies to identify complex models.
Availability: The MATLAB code of the prototype implementation is available on: http://bioinformatics.tudelft.nl/ or http://bioinformatics.nki.nl/
Contact: m.j.t.reinders@tudelft.nl; l.wessels@nki.nl
Next-generation VariationHunter: combinatorial algorithms for transposon insertion discovery
Authors: Hormozdiari Fereydoun , Hajirasouliha Iman , Dao Phuong , Hach Faraz , Yorukoglu Deniz , Alkan Can , Eichler Evan E. , Sahinalp S. Cenk 
Published: June 2010

Abstract
Recent years have witnessed an increase in research activity for the detection of structural variants (SVs) and their association to human disease. The advent of next-generation sequencing technologies make it possible to extend the scope of structural variation studies to a point previously unimaginable as exemplified by the 1000 Genomes Project. Although various computational methods have been described for the detection of SVs, no such algorithm is yet fully capable of discovering transposon insertions, a very important class of SVs to the study of human evolution and disease. In this article, we provide a complete and novel formulation to discover both loci and classes of transposons inserted into genomes sequenced with high-throughput sequencing technologies. In addition, we also present ‘conflict resolution’ improvements to our earlier combinatorial SV detection algorithm (VariationHunter) by taking the diploid nature of the human genome into consideration. We test our algorithms with simulated data from the Venter genome (HuRef) and are able to discover &gt;85% of transposon insertion events with precision of &gt;90%. We also demonstrate that our conflict resolution algorithm (denoted as VariationHunter-CR) outperforms current state of the art (such as original VariationHunter, BreakDancer and MoDIL) algorithms when tested on the genome of the Yoruba African individual (NA18507).
Availability: The implementation of algorithm is available at http://compbio.cs.sfu.ca/strvar.htm.
Contact: eee@gs.washington.edu; cenk@cs.sfu.ca
Supplementary information: Supplementary data are available at Bioinformatics online.
Quantifying the distribution of probes between subcellular locations using unsupervised pattern unmixing
Authors: Coelho Luis Pedro , Peng Tao , Murphy Robert F. 
Published: June 2010

Abstract
Motivation: Proteins exhibit complex subcellular distributions, which may include localizing in more than one organelle and varying in location depending on the cell physiology. Estimating the amount of protein distributed in each subcellular location is essential for quantitative understanding and modeling of protein dynamics and how they affect cell behaviors. We have previously described automated methods using fluorescent microscope images to determine the fractions of protein fluorescence in various subcellular locations when the basic locations in which a protein can be present are known. As this set of basic locations may be unknown (especially for studies on a proteome-wide scale), we here describe unsupervised methods to identify the fundamental patterns from images of mixed patterns and estimate the fractional composition of them.
Methods: We developed two approaches to the problem, both based on identifying types of objects present in images and representing patterns by frequencies of those object types. One is a basis pursuit method (which is based on a linear mixture model), and the other is based on latent Dirichlet allocation (LDA). For testing both approaches, we used images previously acquired for testing supervised unmixing methods. These images were of cells labeled with various combinations of two organelle-specific probes that had the same fluorescent properties to simulate mixed patterns of subcellular location.
Results: We achieved 0.80 and 0.91 correlation between estimated and underlying fractions of the two probes (fundamental patterns) with basis pursuit and LDA approaches, respectively, indicating that our methods can unmix the complex subcellular distribution with reasonably high accuracy.
Availability: http://murphylab.web.cmu.edu/software
Contact: murphy@cmu.edu
Efficient identification of identical-by-descent status in pedigrees with many untyped individuals
Authors: Li Xin , Yin Xiaolin , Li Jing 
Published: June 2010

Abstract
Motivation: Inference of identical-by-descent (IBD) probabilities is the key in family-based linkage analysis. Using high-density single nucleotide polymorphism (SNP) markers, one can almost always infer haplotype configurations of each member in a family given all individuals being typed. Consequently, the IBD status can be obtained directly from haplotype configurations. However, in reality, many family members are not typed due to practical reasons. The problem of IBD/haplotype inference is much harder when treating untyped individuals as missing.
Results: We present a novel hidden Markov model (HMM) approach to infer the IBD status in a pedigree with many untyped members using high-density SNP markers. We introduce the concept of inheritance-generating function, defined for any pair of alleles in a descent graph based on a pedigree structure. We derive a recursive formula for efficient calculation of the inheritance-generating function. By aggregating all possible inheritance patterns via an explicit representation of the number and lengths of all possible paths between two alleles, the inheritance-generating function provides a convenient way to theoretically derive the transition probabilities of the HMM. We further extend the basic HMM to incorporate population linkage disequilibrium (LD). Pedigree-wise IBD sharing can be constructed based on pair-wise IBD relationships. Compared with traditional approaches for linkage analysis, our new model can efficiently infer IBD status without enumerating all possible genotypes and transmission patterns of untyped members in a family. Our approach can be reliably applied on large pedigrees with many untyped members, and the inferred IBD status can be used for non-parametric genome-wide linkage analysis.
Availability: The algorithm is implemented in Matlab and is freely available upon request.
Contact: jingli@cwru.edu
Supplementary information: Supplementary data are available on Bioinformatics online.
First Report of Shallot latent virus in Garlic in Argentina
Authors: Torrico A. K. , Cafrune E. E. , Conci V. C. 
Published: June 2010

Because of exclusively agamic propagation, garlic is commonly infected with a virus complex mainly composed of species within the genera Potyvirus, Allexivirus, and Carlavirus. This virus complex causes leaf striping that ranges from various shades of green to yellow and results in yield losses (2,4). Onion yellow dwarf virus, Leek yellow stripe virus (potyviruses), Garlic virus A, Garlic virus C (allexiviruses), and Garlic common latent virus (carlavirus) have been detected in Argentina previously (1,2). Recently, Shallot latent virus (SLV; another carlavirus) was detected in 25 of 30 garlic plants (cv. Morado) growing in four different fields near Córdoba, Argentina by double-antibody sandwich (DAS)-ELISA using BIOREBA (Reinach, Switzerland) antibodies. To confirm the presence of the virus, DAS-ELISA-positive plants were also analyzed by one-step reverse transcription (RT)-PCR using the Access RT-PCR system (Promega, Madison, WI) with specific primers reported by Tsuneyoshi et al. (3). RNA extractions were performed from 100 mg of leaves with the Qiagen RNeasy Plant Mini Kit (Qiagen, Valencia, CA). Primers used were Car-V1 (5′-AAACCTTTTGGTTCACTTTAGG-3′); Car-V2 (5′-AGGTGCATTGTTATCATTACTGG-3′); and Car-Cp3 (5′-GCGTGCTATATTTAAGTTGCATAC-3′). Primer pairs Car-V1/Car-Cp3 and Car-V2/Car-Cp3 were used for the amplification of the coat protein (CP) gene of SLV and an isolate of SLV formerly known as Garlic latent virus, respectively. Fragments of 992 bp and 1,079 bp were amplified with these primer pairs, respectively. The RT-PCR products were cloned with the TOPO TA Cloning Kit in the 3.9-kb pCR-TOPO vector (Qiagen). The nucleotide sequences of both fragments were determined and were found to be identical (GenBank No. GU355922) showing 94.2% nt sequence identity with the CP gene of an isolate of SLV from Indonesian garlic (GenBank No. AB004686) formerly referred to as Garlic latent virus (3). Consequently, the Argentinean virus is now considered a garlic isolate of SLV. References: (1) E. Cafrune et al. Plant Dis. 90:898, 2006. (2) V. C. Conci. Virus y Fitoplasmas de Ajo. Page 267 in: 50 Temas Sobre Producción de Ajo. Vol. 3. J. L. Burba, ed. Ediciones INTA, Mendoza, Argentina. 1997. (3) T. Tsuneyoshi et al. Arch. Virol. 143:1093, 1998. (4) D. G. A. Walkey and D. N. Antill. J. Hortic. Sci. 64:53, 1989.
Requiring suspended drunk drivers to install alcohol interlocks to reinstate their licenses: effective?
Authors: Voas Robert B. , Tippetts S. Scott , Fisher Deborah , Grosz Milton 
Published: June 2010

ABSTRACTAims  To evaluate a new method being used by some states for motivating interlock installation by requiring it as a prerequisite to reinstatement of the driver's license.Design  The driving records of Florida DWI offenders convicted between July 2002 and June 2008 were analyzed to determine the proportion of offenders subject to the interlock requirement who installed interlocks.Setting  Most driving‐while‐impaired (DWI) offenders succeed in avoiding state laws requiring the installation of a vehicle alcohol interlock.Participants  A total of 82 318 Florida DWI offenders.Findings  Due to long periods of complete suspension when no driving was permitted and the failure to complete all the requirements imposed by the court, only 21 377 of the 82 318 offenders studied qualified for reinstatement, but 93% of those who qualified did install interlocks to be reinstated.Conclusions  Because of the lengthy license suspensions and other barriers that the offenders face in qualifying for reinstatement, it is not clear that requiring a period on the interlock as a prerequisite to reinstating will greatly increase the current installment rate.
A single‐stranded conformational polymorphism (SSCP)‐derived quantitative variable to monitor the virulence of a Barley yellow dwarf virus‐PAV (BYDV‐PAV) isolate during adaptation to the TC14 resistant wheat line
Authors: DELAUNAY AGNES , LACROIX CHRISTELLE , MORLIERE STEPHANIE , RIAULT GERARD , CHAIN FLORIAN , TROTTET MAXIME , JACQUOT EMMANUEL 
Published: June 2010

SUMMARYA standardized single‐stranded conformational polymorphism (SSCP) procedure is proposed as an alternative to the time‐consuming biological characterization of Barley yellow dwarf virus‐PAV (BYDV‐PAV) isolates. Using this procedure, six of 21 overlapping regions used to scan the viral genome gave patterns specific to ‘4E’ (avirulent) or ‘4T’ (‘4E’‐derived virulent) isolates. The calibration of samples and integration of SSCP patterns corresponding to the nucleotide region 1482–2023 allowed the estimation of PT values that reflect the proportions of a ‘4T’‐specific band. Analysis of the biological (area under the pathogen progress curve) and molecular (PT) data suggested a positive linear relation between these variables. Moreover, sequence analysis of the nucleotide region 1482–2023 highlighted the presence of a nucleotide polymorphism (C/A1835) which can be considered as a candidate for virus–host interactions linked to the monitored virulence. According to these parameters, PT values associated with ‘4E’‐ and ‘4T’‐derived populations show that: (i) long‐term infection of a BYDV‐PAV isolate on the ‘TC14’ resistant host leads to the fixation of virulent individuals in viral populations; and (ii) the introduction of susceptible hosts in successive ‘TC14’ infections results in the maintenance of low virulence of the populations. Thus, the presented study demonstrates that SSCP is a useful tool for monitoring viral populations during the host adaptation process. The described impact of host alternation provides new opportunities for the use of the ‘TC14’ resistance source in BYDV‐resistant breeding programmes. This study is part of the global effort made by the scientific community to propose sustainable alternatives to the chemical control of this viral disease.