bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reaction graph kernels predict EC numbers of unknown enzymatic reactions in plant secondary metabolism
Authors: Saigo Hiroto , Hattori Masahiro , Kashima Hisashi , Tsuda Koji 
Published: January 2010

AbstractBackgroundUnderstanding of secondary metabolic pathway in plant is essential for finding druggable candidate enzymes. However, there are many enzymes whose functions are not yet discovered in organism-specific metabolic pathways. Towards identifying the functions of those enzymes, assignment of EC numbers to the enzymatic reactions they catalyze plays a key role, since EC numbers represent the categorization of enzymes on one hand, and the categorization of enzymatic reactions on the other hand.ResultsWe propose reaction graph kernels for automatically assigning EC numbers to unknown enzymatic reactions in a metabolic network. Reaction graph kernels compute similarity between two chemical reactions considering the similarity of chemical compounds in reaction and their relationships. In computational experiments based on the KEGG/REACTION database, our method successfully predicted the first three digits of the EC number with 83% accuracy. We also exhaustively predicted missing EC numbers in plant's secondary metabolism pathway. The prediction results of reaction graph kernels on 36 unknown enzymatic reactions are compared with an expert's knowledge. Using the same data for evaluation, we compared our method with E-zyme, and showed its ability to assign more number of accurate EC numbers.ConclusionReaction graph kernels are a new metric for comparing enzymatic reactions.
Efficient genome-scale phylogenetic analysis under the duplication-loss and deep coalescence cost models
Authors: Bansal Mukul S , Burleigh J Gordon , Eulenstein Oliver 
Published: January 2010

Abstract

Background
Genomic data provide a wealth of new information for phylogenetic analysis. Yet making use of this data requires phylogenetic methods that can efficiently analyze extremely large data sets and account for processes of gene evolution, such as gene duplication and loss, incomplete lineage sorting (deep coalescence), or horizontal gene transfer, that cause incongruence among gene trees. One such approach is gene tree parsimony, which, given a set of gene trees, seeks a species tree that requires the smallest number of evolutionary events to explain the incongruence of the gene trees. However, the only existing algorithms for gene tree parsimony under the duplication-loss or deep coalescence reconciliation cost are prohibitively slow for large datasets.

Results
We describe novel algorithms for SPR and TBR based local search heuristics under the duplication-loss cost, and we show how they can be adapted for the deep coalescence cost. These algorithms improve upon the best existing algorithms for these problems by a factor of n, where n is the number of species in the collection of gene trees. We implemented our new SPR based local search algorithm for the duplication-loss cost and demonstrate the tremendous improvement in runtime and scalability it provides compared to existing implementations. We also evaluate the performance of our algorithm on three large-scale genomic data sets.

Conclusion
Our new algorithms enable, for the first time, gene tree parsimony analyses of thousands of genes from hundreds of taxa using the duplication-loss and deep coalescence reconciliation costs. Thus, this work expands both the size of data sets and the range of evolutionary models that can be incorporated into genome-scale phylogenetic analyses.
A novel approach for haplotype-based association analysis using family data
Authors: Chen Yixuan , Li Xin , Li Jing 
Published: January 2010

Abstract

Background
Haplotype-based approaches have been extensively studied for case-control association mapping in recent years. It has been shown that haplotype methods can provide more consistent results comparing to single-locus based approaches, especially in cases where causal variants are not typed. Improved power has been observed by clustering similar or rare haplotypes into groups to reduce the degrees of freedom of association tests. For family-based association studies, one commonly used strategy is Transmission Disequilibrium Tests (TDT), which examine the imbalanced transmission of alleles/haplotypes to affected and normal children. Many extensions have been developed to deal with general pedigrees and continuous traits.

Results
In this paper, we propose a new haplotype-based association method for family data that is different from the TDT framework. Our approach (termed F_HapMiner) is based on our previous successful experiences on haplotype inference from pedigree data and haplotype-based association mapping. It first infers diplotype pairs of each individual in each pedigree assuming no recombination within a family. A phenotype score is then defined for each founder haplotype. Finally, F_HapMiner applies a clustering algorithm on those founder haplotypes based on their similarities and identifies haplotype clusters that show significant associations with diseases/traits. We have performed extensive simulations based on realistic assumptions to evaluate the effectiveness of the proposed approach by considering different factors such as allele frequency, linkage disequilibrium (LD) structure, disease model and sample size. Comparisons with single-locus and haplotype-based TDT methods demonstrate that our approach consistently outperforms the TDT-based approaches regardless of disease models, local LD structures or allele/haplotype frequencies.

Conclusion
We present a novel haplotype-based association approach using family data. Experiment results demonstrate that it achieves significantly higher power than TDT-based approaches.
An automated framework for understanding structural variations in the binding grooves of MHC class II molecules
Authors: Yeturu Kalidas , Utriainen Tapani , Kemp Graham JL , Chandra Nagasuma 
Published: January 2010

Abstract

Background
MHC/HLA class II molecules are important components of the immune system and play a critical role in processes such as phagocytosis. Understanding peptide recognition properties of the hundreds of MHC class II alleles is essential to appreciate determinants of antigenicity and ultimately to predict epitopes. While there are several methods for epitope prediction, each differing in their success rates, there are no reports so far in the literature to systematically characterize the binding sites at the structural level and infer recognition profiles from them.

Results
Here we report a new approach to compare the binding sites of MHC class II molecules using their three dimensional structures. We use a specifically tuned version of our recent algorithm, PocketMatch. We show that our methodology is useful for classification of MHC class II molecules based on similarities or differences among their binding sites. A new module has been used to define binding sites in MHC molecules. Comparison of binding sites of 103 MHC molecules, both at the whole groove and individual sub-pocket levels has been carried out, and their clustering patterns analyzed. While clusters largely agree with serotypic classification, deviations from it and several new insights are obtained from our study. We also present how differences in sub-pockets of molecules associated with a pair of autoimmune diseases, narcolepsy and rheumatoid arthritis, were captured by PocketMatch
13.

Conclusion
The systematic framework for understanding structural variations in MHC class II molecules enables large scale comparison of binding grooves and sub-pockets, which is likely to have direct implications towards predicting epitopes and understanding peptide binding preferences.
Genome-wide sequence-based prediction of peripheral proteins using a novel semi-supervised learning technique
Authors: Bhardwaj Nitin , Gerstein Mark , Lu Hui 
Published: January 2010

Abstract

Background
In supervised learning, traditional approaches to building a classifier use two sets of examples with pre-defined classes along with a learning algorithm. The main limitation of this approach is that examples from both classes are required which might be infeasible in certain cases, especially those dealing with biological data. Such is the case for membrane-binding peripheral domains that play important roles in many biological processes, including cell signaling and membrane trafficking by reversibly binding to membranes. For these domains, a well-defined positive set is available with domains known to bind membrane along with a large unlabeled set of domains whose membrane binding affinities have not been measured. The aforementioned limitation can be addressed by a special class of semi-supervised machine learning called positive-unlabeled (PU) learning that uses a positive set with a large unlabeled set.

Methods
In this study, we implement the first application of PU-learning to a protein function prediction problem: identification of peripheral domains. PU-learning starts by identifying reliable negative (RN) examples iteratively from the unlabeled set until convergence and builds a classifier using the positive and the final RN set. A data set of 232 positive cases and ~3750 unlabeled ones were used to construct and validate the protocol.

Results
Holdout evaluation of the protocol on a left-out positive set showed that the accuracy of prediction reached up to 95% during two independent implementations.

Conclusion
These results suggest that our protocol can be used for predicting membrane-binding properties of a wide variety of modular domains. Protocols like the one presented here become particularly useful in the case of availability of information from one class only.
1,25 dihydroxyvitamin D-mediated orchestration of anticancer, transcript-level effects in the immortalized, non-transformed prostate epithelial cell line, RWPE1
Authors: Kovalenko Pavlo L , Zhang Zhentao , Cui Min , Clinton Steve K , Fleet James C 
Published: January 2010

AbstractBackgroundProstate cancer is the second leading cause of cancer mortality among US men. Epidemiological evidence suggests that high vitamin D status protects men from prostate cancer and the active form of vitamin D, 1α,25 dihydroxyvitamin D3(1,25(OH)2D) has anti-cancer effects in cultured prostate cells. Still, the molecular mechanisms and the gene targets for vitamin D-mediated prostate cancer prevention are unknown.ResultsWe examined the effect of 1,25(OH)2D (+/- 100 nM, 6, 24, 48 h) on the transcript profile of proliferating RWPE1 cells, an immortalized, non-tumorigenic prostate epithelial cell line that is growth arrested by 1,25(OH)2D (Affymetrix U133 Plus 2.0, n = 4/treatment per time and dose). Our analysis revealed many transcript level changes at a 5% false detection rate: 6 h, 1571 (61% up), 24 h, 1816 (60% up), 48 h, 3566 (38% up). 288 transcripts were regulated similarly at all time points (182 up, 80 down) and many of the promoters for these transcripts contained putative vitamin D response elements. Functional analysis by pathway or Gene Set Analysis revealed early suppression of WNT, Notch, NF-kB, and IGF1 signaling. Transcripts related to inflammation were suppressed at 6 h (e.g. IL-1 pathway) and suppression of proinflammatory pathways continued at later time points (e.g. IL-17 and IL-6 pathways). There was also evidence for induction of anti-angiogenic pathways and induction of transcripts for protection from oxidative stress or maintenance of cell redox homeostasis at 6 h.ConclusionsOur data reveal of large number of potential new, direct vitamin D target genes relevant to prostate cancer prevention. In addition, our data suggests that rather than having a single strong regulatory effect, vitamin D orchestrates a pattern of changes within prostate epithelial cells that limit or slow carcinogenesis.
Adaptation of NS cells growth and differentiation to high-throughput screening-compatible plates
Authors: Garavaglia Alessia , Moiana Alessia , Camnasio Stefano , Bolognini Daniele , Papait Roberto , Rigamonti Dorotea , Cattaneo Elena 
Published: January 2010

Abstract

Background
There is an urgent need of neuronal cell models to be applied to high-throughput screening settings while recapitulating physiological and/or pathological events occurring in the Central Nervous System (CNS). Stem cells offer a great opportunity in this direction since their self renewal capacity allows for large scale expansion. Protocols for directed differentiation also promise to generate populations of biochemically homogenous neuronal progenies. NS (Neural Stem) cells are a novel population of stem cells that undergo symmetric cell division in monolayer and chemically defined media, while remaining highly neurogenic.

Results
We report the full adaptation of the NS cell systems for their growth and neuronal differentiation to 96- and 384-well microplates. This optimized system has also been exploited in homogeneous and high-content assays.

Conclusions
Our results show that these mouse NS cells may be suitable for a series of applications in high-throughput format.
Chronic non-transmural infarction has a delayed recovery of function following revascularization
Authors: Ugander Martin , Cain Peter A , Johnsson Per , Palmer John , Arheden Håkan 
Published: January 2010

Abstract

Background
The time course of regional functional recovery following revascularization with regards to the presence or absence of infarction is poorly known. We studied the effect of the presence of chronic non-transmural infarction on the time course of recovery of myocardial perfusion and function after elective revascularization.

Methods
Eighteen patients (mean age 69, range 52-84, 17 men) prospectively underwent cine magnetic resonance imaging (MRI), delayed contrast enhanced MRI and rest/stress 99m-Tc-tetrofosmin single photon emission computed tomography (SPECT) before, one and six months after elective coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI).

Results
Dysfunctional myocardial segments (n = 337/864, 39%) were classified according to the presence (n = 164) or absence (n = 173) of infarction. Infarct transmurality in dysfunctional segments was largely non-transmural (transmurality = 31 ± 22%). Quantitative stress perfusion and wall thickening increased at one month in dysfunctional segments without infarction (p < 0.001), with no further improvement at six months. Despite improvements in stress perfusion at one month (p < 0.001), non-transmural infarction displayed a slower and lesser improvement in wall thickening at one (p < 0.05) and six months (p < 0.001).

Conclusions
Dysfunctional segments without infarction represent repetitively stunned or hibernating myocardium, and these segments improved both perfusion and function within one month after revascularization with no improvement thereafter. Although dysfunctional segments with non-transmural infarction improved in perfusion at one month, functional recovery was mostly seen between one and six months, possibly reflecting a more severe ischemic burden. These findings may be of value in the clinical assessment of regional functional recovery in the time period after revascularization.
Partner notification for sexually transmitted infections in developing countries: a systematic review
Authors: Alam Nazmul , Chamot Eric , Vermund Sten H , Streatfield Kim , Kristensen Sibylle 
Published: January 2010

Abstract

Background
The feasibility and acceptability of partner notification (PN) for sexually transmitted infections (STIs) in developing countries was assessed through a comprehensive literature review, to help identify future intervention needs.

Methods
The Medline, Embase, and Google Scholar databases were searched to identify studies published between January 1995 and December 2007 on STI PN in developing countries. A systematic review of the research extracted information on: (1) willingness of index patients to notify partners; (2) the proportion of partners notified or referred; (3) client-reported barriers in notifying partners; (4) infrastructure barriers in notifying partners; and (5) PN approaches that were evaluated in developing countries.

Results
Out of 609 screened articles, 39 met our criteria. PN outcome varied widely and was implemented more often for spousal partners than for casual or commercial partners. Reported barriers included sociocultural factors such as stigma, fear of abuse for having an STI, and infrastructural factors related to the limited number of STD clinics, and trained providers and reliable diagnostic methods. Client-oriented counselling was found to be effective in improving partner referral outcomes.

Conclusions
STD clinics can improve PN with client-oriented counselling, which should help clients to overcome perceived barriers. The authors speculate that well-designed PN interventions to evaluate the impact on STI prevalence and incidence along with cost-effectiveness components will motivate policy makers in developing countries to allocate more resources towards STI management.
Expression and display of UreA of Helicobacter acinonychis on the surface of Bacillus subtilis spores
Authors: Hinc Krzysztof , Isticato Rachele , Dembek Marcin , Karczewska Joanna , Iwanicki Adam , Peszyńska-Sularz Grażyna , De Felice Maurilio , Obuchowski Michał , Ricca Ezio 
Published: January 2010

Abstract

Background
The bacterial endospore (spore) has recently been proposed as a new surface display system. Antigens and enzymes have been successfully exposed on the surface layers of the Bacillus subtilis spore, but only in a few cases the efficiency of expression and the effective surface display and have been determined. We used this heterologous expression system to produce the A subunit of the urease of the animal pathogen Helicobater acinonychis. Ureases are multi-subunit enzymes with a central role in the virulence of various bacterial pathogens and necessary for colonization of the gastric mucosa by the human pathogen H. pylori. The urease subunit UreA has been recognized as a major antigen, able to induce high levels of protection against challenge infections.

Results
We expressed UreA from H. acinonychis on the B. subtilis spore coat by using three different spore coat proteins as carriers and compared the efficiency of surface expression and surface display obtained with the three carriers. A combination of western-, dot-blot and immunofluorescence microscopy allowed us to conclude that, when fused to CotB, UreA is displayed on the spore surface (ca. 1 × 103 recombinant molecules per spore), whereas when fused to CotC, although most efficiently expressed (7-15 × 103 recombinant molecules per spore) and located in the coat layer, it is not displayed on the surface. Experiments with CotG gave results similar to those with CotC, but the CotG-UreA recombinant protein appeared to be partially processed.

Conclusion
UreA was efficiently expressed on the spore coat of B. subtilis when fused to CotB, CotC or CotG. Of these three coat proteins CotC allows the highest efficiency of expression, whereas CotB is the most appropriate for the display of heterologous proteins on the spore surface.
Molecular characterization of the virulent infectious hematopoietic necrosis virus (IHNV) strain 220-90
Authors: Ammayappan Arun , LaPatra Scott E , Vakharia Vikram N 
Published: January 2010

Abstract

Background
Infectious hematopoietic necrosis virus (IHNV) is the type species of the genus Novirhabdovirus, within the family Rhabdoviridae, infecting several species of wild and hatchery reared salmonids. Similar to other rhabdoviruses, IHNV has a linear single-stranded, negative-sense RNA genome of approximately 11,000 nucleotides. The IHNV genome encodes six genes; the nucleocapsid, phosphoprotein, matrix protein, glycoprotein, non-virion protein and polymerase protein genes, respectively. This study describes molecular characterization of the virulent IHNV strain 220-90, belonging to the M genogroup, and its phylogenetic relationships with available sequences of IHNV isolates worldwide.

Results
The complete genomic sequence of IHNV strain 220-90 was determined from the DNA of six overlapping clones obtained by RT-PCR amplification of genomic RNA. The complete genome sequence of 220-90 comprises 11,133 nucleotides (GenBank GQ413939) with the gene order of 3'-N-P-M-G-NV-L-5'. These genes are separated by conserved gene junctions, with di-nucleotide gene spacers. An additional uracil nucleotide was found at the end of the 5'-trailer region, which was not reported before in other IHNV strains. The first 15 of the 16 nucleotides at the 3'- and 5'-termini of the genome are complementary, and the first 4 nucleotides at 3'-ends of the IHNV are identical to other novirhadoviruses. Sequence homology and phylogenetic analysis of the glycoprotein genes show that 220-90 strain is 97% identical to most of the IHNV strains. Comparison of the virulent 220-90 genomic sequences with less virulent WRAC isolate shows more than 300 nucleotides changes in the genome, which doesn't allow one to speculate putative residues involved in the virulence of IHNV.

Conclusion
We have molecularly characterized one of the well studied IHNV isolates, 220-90 of genogroup M, which is virulent for rainbow trout, and compared phylogenetic relationship with North American and other strains. Determination of the complete nucleotide sequence is essential for future studies on pathogenesis of IHNV using a reverse genetics approach and developing efficient control strategies.