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  • Institute of Physics  (1,176)
  • Oxford University Press  (664)
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  • 1
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    Extending gene ontology with gene association networks (2016)
    Oxford University Press
    Details
    Publication Date: 2016-04-08
    Description: Motivation: Gene ontology (GO) is a widely used resource to describe the attributes for gene products. However, automatic GO maintenance remains to be difficult because of the complex logical reasoning and the need of biological knowledge that are not explicitly represented in the GO. The existing studies either construct whole GO based on network data or only infer the relations between existing GO terms. None is purposed to add new terms automatically to the existing GO. Results: We proposed a new algorithm ‘GOExtender’ to efficiently identify all the connected gene pairs labeled by the same parent GO terms. GOExtender is used to predict new GO terms with biological network data, and connect them to the existing GO. Evaluation tests on biological process and cellular component categories of different GO releases showed that GOExtender can extend new GO terms automatically based on the biological network. Furthermore, we applied GOExtender to the recent release of GO and discovered new GO terms with strong support from literature. Availability and implementation: Software and supplementary document are available at www.msu.edu/%7Ejinchen/GOExtender Contact: jinchen@msu.edu or ydwang@hit.edu.cn Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 2
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    CR Cistrome: a ChIP-Seq database for chromatin regulators and histone modification linkages in human and mouse (2013)
    Oxford University Press
    Details
    Publication Date: 2013-12-29
    Description: Diversified histone modifications (HMs) are essential epigenetic features. They play important roles in fundamental biological processes including transcription, DNA repair and DNA replication. Chromatin regulators (CRs), which are indispensable in epigenetics, can mediate HMs to adjust chromatin structures and functions. With the development of ChIP-Seq technology, there is an opportunity to study CR and HM profiles at the whole-genome scale. However, no specific resource for the integration of CR ChIP-Seq data or CR-HM ChIP-Seq linkage pairs is currently available. Therefore, we constructed the CR Cistrome database, available online at http://compbio.tongji.edu.cn/cr and http://cistrome.org/cr/ , to further elucidate CR functions and CR-HM linkages. Within this database, we collected all publicly available ChIP-Seq data on CRs in human and mouse and categorized the data into four cohorts: the reader, writer, eraser and remodeler cohorts, together with curated introductions and ChIP-Seq data analysis results. For the HM readers, writers and erasers, we provided further ChIP-Seq analysis data for the targeted HMs and schematized the relationships between them. We believe CR Cistrome is a valuable resource for the epigenetics community.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 3
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    Epidemic Clones, Oceanic Gene Pools, and Eco-LD in the Free Living Marine Pathogen Vibrio parahaemolyticus (2015)
    Oxford University Press
    Details
    Publication Date: 2015-05-30
    Description: We investigated global patterns of variation in 157 whole-genome sequences of Vibrio parahaemolyticus , a free-living and seafood associated marine bacterium. Pandemic clones, responsible for recent outbreaks of gastroenteritis in humans, have spread globally. However, there are oceanic gene pools, one located in the oceans surrounding Asia and another in the Mexican Gulf. Frequent recombination means that most isolates have acquired the genetic profile of their current location. We investigated the genetic structure in the Asian gene pool by calculating the effective population size in two different ways. Under standard neutral models, the two estimates should give similar answers but we found a 27-fold difference. We propose that this discrepancy is caused by the subdivision of the species into a hundred or more ecotypes which are maintained stably in the population. To investigate the genetic factors involved, we used 51 unrelated isolates to conduct a genome-wide scan for epistatically interacting loci. We found a single example of strong epistasis between distant genome regions. A majority of strains had a type VI secretion system associated with bacterial killing. The remaining strains had genes associated with biofilm formation and regulated by cyclic dimeric GMP signaling. All strains had one or other of the two systems and none of isolate had complete complements of both systems, although several strains had remnants. Further "top down" analysis of patterns of linkage disequilibrium within frequently recombining species will allow a detailed understanding of how selection acts to structure the pattern of variation within natural bacterial populations.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
    Published by Oxford University Press
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  • 4
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    Sprites: detection of deletions from sequencing data by re-aligning split reads (2016)
    Oxford University Press
    Details
    Publication Date: 2016-06-16
    Description: Motivation : Advances of next generation sequencing technologies and availability of short read data enable the detection of structural variations (SVs). Deletions, an important type of SVs, have been suggested in association with genetic diseases. There are three types of deletions: blunt deletions, deletions with microhomologies and deletions with microsinsertions. The last two types are very common in the human genome, but they pose difficulty for the detection. Furthermore, finding deletions from sequencing data remains challenging. It is highly appealing to develop sensitive and accurate methods to detect deletions from sequencing data, especially deletions with microhomology and deletions with microinsertion. Results : We present a novel method called Sprites (SPlit Read re-alIgnment To dEtect Structural variants) which finds deletions from sequencing data. It aligns a whole soft-clipping read rather than its clipped part to the target sequence, a segment of the reference which is determined by spanning reads, in order to find the longest prefix or suffix of the read that has a match in the target sequence. This alignment aims to solve the problem of deletions with microhomologies and deletions with microinsertions. Using both simulated and real data we show that Sprites performs better on detecting deletions compared with other current methods in terms of F-score. Availability and implementation : Sprites is open source software and freely available at https://github.com/zhangzhen/sprites . Contact: jxwang@mail.csu.edu.cn Supplementary data: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 5
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    Meta-analysis of genome-wide association studies in five cohorts reveals common variants in RBFOX1, a regulator of tissue-specific splicing, associated with refractive error (2013)
    Stambolian, D., Wojciechowski, R., Oexle, K., Pirastu, M., Li, X., Raffel, L. J., Cotch, M. F., Chew, E. Y., Klein, B., Klein, R., Wong, T. Y., Simpson, C. L., Klaver, C. C. W., van Duijn, C. M., Verhoeven, V. J. M., Baird, P. N., Vitart, V., Paterson, A. D., Mitchell, P., Saw, S. M., Fossarello, M., Kazmierkiewicz, K., Murgia, F., Portas, L., Schache, M., Richardson, A., Xie, J., Wang, J. J., Rochtchina, E., DCCT/EDIC Research Group, Viswanathan, A. C., Hayward, C., Wright, A. F., Polasek, O., Campbell, H., Rudan, I., Oostra, B. A., Uitterlinden, A. G., Hofman, A., Rivadeneira, F., Amin, N., Karssen, L. C., Vingerling, J. R., Hosseini, S. M., Doring, A., Bettecken, T., Vatavuk, Z., Gieger, C., Wichmann, H.- E., Wilson, J. F., Fleck, B., Foster, P. J., Topouzis, F., McGuffin, P., Sim, X., Inouye, M., Holliday, E. G., Attia, J., Scott, R. J., Rotter, J. I., Meitinger, T., Bailey-Wilson, J. E.
    Oxford University Press
    Details
    Publication Date: 2013-06-07
    Description: Visual refractive errors (REs) are complex genetic traits with a largely unknown etiology. To date, genome-wide association studies (GWASs) of moderate size have identified several novel risk markers for RE, measured here as mean spherical equivalent (MSE). We performed a GWAS using a total of 7280 samples from five cohorts: the Age-Related Eye Disease Study (AREDS); the KORA study (‘Cooperative Health Research in the Region of Augsburg’); the Framingham Eye Study (FES); the Ogliastra Genetic Park-Talana (OGP-Talana) Study and the Multiethnic Study of Atherosclerosis (MESA). Genotyping was performed on Illumina and Affymetrix platforms with additional markers imputed to the HapMap II reference panel. We identified a new genome-wide significant locus on chromosome 16 (rs10500355, P = 3.9 x 10 –9 ) in a combined discovery and replication set (26 953 samples). This single nucleotide polymorphism (SNP) is located within the RBFOX1 gene which is a neuron-specific splicing factor regulating a wide range of alternative splicing events implicated in neuronal development and maturation, including transcription factors, other splicing factors and synaptic proteins.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 6
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    A Trust Routing for Multimedia Social Networks (2015)
    Oxford University Press
    Details
    Publication Date: 2015-03-27
    Description: Due to the disconnected and store-and-forward architecture in multimedia social networks (MSNs), routing becomes a great challenge with the frequent path disruptions. Moreover, some nodes in MSNs tend to be selfish or malicious, e.g. they sometimes will not forward packets for other nodes or will launch passive and active attacks in order to save their limited resources such as bandwidth, battery or storage. In order to address this issue, we propose a fuzzy-based trust management technique for context-based routing in MSNs. We incorporate social trust metrics and quality of service metrics into our trust model. By adopting fuzzy sets, every node can evaluate the credibility of other nodes based on the direct and indirect relationship. By ranking all its neighbors according to the trust values, each node can purge untrustworthy nodes. Since only trusted nodes’ packets will be forwarded, the selfish or malicious nodes have the incentive to behave well again in order to be able to send packets. Additionally, we perform extensive security and performance evaluation with the opportunistic network environment simulator. The simulation results show that our trust model can dynamically update the trust value in real time, effectively measure the trust relationship and correctly identify malicious or selfish nodes. Furthermore, the proposed trust routing is a lightweight protocol balancing the message overhead and delivery ratio.
    Print ISSN: 0010-4620
    Electronic ISSN: 1460-2067
    Topics: Computer Science
    Published by Oxford University Press
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  • 7
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    Lnc2Cancer: a manually curated database of experimentally supported lncRNAs associated with various human cancers (2016)
    Oxford University Press
    Details
    Publication Date: 2016-01-07
    Description: Lnc2Cancer ( http://www.bio-bigdata.net/lnc2cancer ) is a manually curated database of cancer-associated long non-coding RNAs (lncRNAs) with experimental support that aims to provide a high-quality and integrated resource for exploring lncRNA deregulation in various human cancers. LncRNAs represent a large category of functional RNA molecules that play a significant role in human cancers. A curated collection and summary of deregulated lncRNAs in cancer is essential to thoroughly understand the mechanisms and functions of lncRNAs. Here, we developed the Lnc2Cancer database, which contains 1057 manually curated associations between 531 lncRNAs and 86 human cancers. Each association includes lncRNA and cancer name, the lncRNA expression pattern, experimental techniques, a brief functional description, the original reference and additional annotation information. Lnc2Cancer provides a user-friendly interface to conveniently browse, retrieve and download data. Lnc2Cancer also offers a submission page for researchers to submit newly validated lncRNA-cancer associations. With the rapidly increasing interest in lncRNAs, Lnc2Cancer will significantly improve our understanding of lncRNA deregulation in cancer and has the potential to be a timely and valuable resource.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 8
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    Structural basis for the Smad5 MH1 domain to recognize different DNA sequences (2015)
    Oxford University Press
    Details
    Publication Date: 2015-10-15
    Description: Smad proteins are important intracellular mediators of TGF-β signalling, which transmit signals directly from cell surface receptors to the nucleus. The MH1 domain of Smad plays a key role in DNA recognition. Two types of DNA sequence were identified as Smad binding motifs: the Smad binding element (SBE) and the GC-rich sequence. Here we report the first crystal structure of the Smad5 MH1 domain in complex with the GC-rich sequence. Compared with the Smad5-MH1/SBE complex structure, the Smad5 MH1 domain contacts the GC-rich site with the same β-hairpin, but the detailed interaction modes are different. Conserved β-hairpin residues make base specific contacts with the minimal GC-rich site, 5'-GGC-3'. The assembly of Smad5-MH1 on the GC-rich DNA also results in distinct DNA conformational changes. Moreover, the crystal structure of Smad5-MH1 in complex with a composite DNA sequence demonstrates that the MH1 domain is targeted to each binding site (GC-rich or SBE) with modular binding modes, and the length of the DNA spacer affects the MH1 assembly. In conclusion, our work provides the structural basis for the recognition and binding specificity of the Smad MH1 domain with the DNA targets.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 9
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    The deepest X-ray view of high-redshift galaxies: constraints on low-rate black hole accretion (2016)
    Oxford University Press
    Details
    Publication Date: 2016-09-10
    Description: We exploit the 7 Ms Chandra observations in the Chandra  Deep Field-South (CDF-S), the deepest X-ray survey to date, coupled with CANDELS/GOODS-S data, to measure the total X-ray emission arising from 2076 galaxies at 3.5 ≤ z 〈 6.5. This aim is achieved by stacking the Chandra data at the positions of optically selected galaxies, reaching effective exposure times of ≥10 9 s. We detect significant (〉3.7) X-ray emission from massive galaxies at z 4. We also report the detection of massive galaxies at z 5 at a 99.7 per cent confidence level (2.7), the highest significance ever obtained for X-ray emission from galaxies at such high redshifts. No significant signal is detected from galaxies at even higher redshifts. The stacking results place constraints on the BHAD associated with the known high-redshift galaxy samples, as well as on the SFRD at high redshift, assuming a range of prescriptions for X-ray emission due to X- ray binaries. We find that the X-ray emission from our sample is likely dominated by processes related to star formation. Our results show that low-rate mass accretion on to SMBHs in individually X-ray-undetected galaxies is negligible, compared with the BHAD measured for samples of X-ray detected AGN, for cosmic SMBH mass assembly at high redshift. We also place, for the first time, constraints on the faint-end of the AGN X-ray luminosity function (logL X ~ 42) at z 〉 4, with evidence for fairly flat slopes. The implications of all of these findings are discussed in the context of the evolution of the AGN population at high redshift.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 10
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    Predicting regulatory variants with composite statistic (2016)
    Oxford University Press
    Details
    Publication Date: 2016-09-12
    Description: Motivation: Prediction and prioritization of human non-coding regulatory variants is critical for understanding the regulatory mechanisms of disease pathogenesis and promoting personalized medicine. Existing tools utilize functional genomics data and evolutionary information to evaluate the pathogenicity or regulatory functions of non-coding variants. However, different algorithms lead to inconsistent and even conflicting predictions. Combining multiple methods may increase accuracy in regulatory variant prediction. Results: Here, we compiled an integrative resource for predictions from eight different tools on functional annotation of non-coding variants. We further developed a composite strategy to integrate multiple predictions and computed the composite likelihood of a given variant being regulatory variant. Benchmarked by multiple independent causal variants datasets, we demonstrated that our composite model significantly improves the prediction performance. Availability and Implementation: We implemented our model and scoring procedure as a tool, named PRVCS, which is freely available to academic and non-profit usage at http://jjwanglab.org/PRVCS . Contact: wang.junwen@mayo.edu , jliu@stat.harvard.edu , or limx54@gmail.com Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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