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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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    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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  • 3
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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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  • 4
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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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  • 5
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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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  • 6
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    Planet Hunters IX. KIC 8462852 - where's the flux? (2016)
    Oxford University Press
    Details
    Publication Date: 2016-03-02
    Description: Over the duration of the Kepler mission, KIC 8462852 was observed to undergo irregularly shaped, aperiodic dips in flux of up to ~20 per cent. The dipping activity can last for between 5 and 80 d. We characterize the object with high-resolution spectroscopy, spectral energy distribution fitting, radial velocity measurements, high-resolution imaging, and Fourier analyses of the Kepler light curve. We determine that KIC 8462852 is a typical main-sequence F3 V star that exhibits no significant IR excess, and has no very close interacting companions. In this paper, we describe various scenarios to explain the dipping events observed in the Kepler light curve. We confirm that the dipping signals in the data are not caused by any instrumental or data processing artefact, and thus are astrophysical in origin. We construct scenario-independent constraints on the size and location of a body in the system that are needed to reproduce the observations. We deliberate over several assorted stellar and circumstellar astrophysical scenarios, most of which have problems explaining the data in hand. By considering the observational constraints on dust clumps in orbit around a normal main-sequence star, we conclude that the scenario most consistent with the data in hand is the passage of a family of exocomet or planetesimal fragments, all of which are associated with a single previous break-up event, possibly caused by tidal disruption or thermal processing. The minimum total mass associated with these fragments likely exceeds 10 –6 M , corresponding to an original rocky body of 〉100 km in diameter. We discuss the necessity of future observations to help interpret the system.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 7
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    Functional interplay between SA1 and TRF1 in telomeric DNA binding and DNA-DNA pairing (2016)
    Oxford University Press
    Details
    Publication Date: 2016-07-28
    Description: Proper chromosome alignment and segregation during mitosis depend on cohesion between sister chromatids. Cohesion is thought to occur through the entrapment of DNA within the tripartite ring (Smc1, Smc3 and Rad21) with enforcement from a fourth subunit (SA1/SA2). Surprisingly, cohesin rings do not play a major role in sister telomere cohesion. Instead, this role is replaced by SA1 and telomere binding proteins (TRF1 and TIN2). Neither the DNA binding property of SA1 nor this unique telomere cohesion mechanism is understood. Here, using single-molecule fluorescence imaging, we discover that SA1 displays two-state binding on DNA: searching by one-dimensional (1D) free diffusion versus recognition through subdiffusive sliding at telomeric regions. The AT-hook motif in SA1 plays dual roles in modulating non-specific DNA binding and subdiffusive dynamics over telomeric regions. TRF1 tethers SA1 within telomeric regions that SA1 transiently interacts with. SA1 and TRF1 together form longer DNA–DNA pairing tracts than with TRF1 alone, as revealed by atomic force microscopy imaging. These results suggest that at telomeres cohesion relies on the molecular interplay between TRF1 and SA1 to promote DNA–DNA pairing, while along chromosomal arms the core cohesin assembly might also depend on SA1 1D diffusion on DNA and sequence-specific DNA binding.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 8
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    Mutations of charged amino acids at the cytoplasmic end of transmembrane helix 2 affect transport activity of the budding yeast multidrug resistance protein Pdr5p (2016)
    Oxford University Press
    Details
    Publication Date: 2016-05-11
    Description: Pdr5p is a major ATP-binding cassette (ABC) transporter in Saccharomyces cerevisiae. It displays a sequence and functional homology to the pathogenic Candida albicans multidrug resistance protein Cdr1p. The transmembrane helices of Pdr5p act in substrate recognition, binding, translocation and eventual removal of toxic substances out of the plasma membrane via the formation of a binding pocket. In this study, we identify two novel Pdr5 mutants (E574K and E580K), which exhibit impaired substrate efflux functions. Both mutants remained hypersensitive to all tested Pdr5p substrates without affecting their protein expression levels, localization or ATPase activities. As E574 and E580 are both located adjacent to the predicted cytoplasmic end of transmembrane helix 2, this implies that such charged residues are functionally essential for Pdr5p. Molecular docking studies suggest the possibility that oppositely charged substitution at residue E574 may disturb the interaction between the substrates and Pdr5p, resulting in impaired transport activity. Our results present new evidence, suggesting that transmembrane helix 2 plays an important role for the efflux function of Pdr5p.
    Print ISSN: 1567-1356
    Electronic ISSN: 1567-1364
    Topics: Biology
    Published by Oxford University Press
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  • 9
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    DriverDBv2: a database for human cancer driver gene research (2016)
    Oxford University Press
    Details
    Publication Date: 2016-01-07
    Description: We previously presented DriverDB, a database that incorporates ~6000 cases of exome-seq data, in addition to annotation databases and published bioinformatics algorithms dedicated to driver gene/mutation identification. The database provides two points of view, ‘Cancer’ and ‘Gene’, to help researchers visualize the relationships between cancers and driver genes/mutations. In the updated DriverDBv2 database ( http://ngs.ym.edu.tw/driverdb ) presented herein, we incorporated 〉9500 cancer-related RNA-seq datasets and 〉7000 more exome-seq datasets from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and published papers. Seven additional computational algorithms (meaning that the updated database contains 15 in total), which were developed for driver gene identification, are incorporated into our analysis pipeline, and the results are provided in the ‘Cancer’ section. Furthermore, there are two main new features, ‘Expression’ and ‘Hotspot’, in the ‘Gene’ section. ‘Expression’ displays two expression profiles of a gene in terms of sample types and mutation types, respectively. ‘Hotspot’ indicates the hotspot mutation regions of a gene according to the results provided by four bioinformatics tools. A new function, ‘Gene Set’, allows users to investigate the relationships among mutations, expression levels and clinical data for a set of genes, a specific dataset and clinical features.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 10
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    Inference on gravitational waves from coalescences of stellar-mass compact objects and intermediate-mass black holes (2016)
    Oxford University Press
    Details
    Publication Date: 2016-03-08
    Description: Gravitational waves from coalescences of neutron stars or stellar-mass black holes into intermediate-mass black holes (IMBHs) of 100 solar masses represent one of the exciting possible sources for advanced gravitational-wave detectors. These sources can provide definitive evidence for the existence of IMBHs, probe globular-cluster dynamics, and potentially serve as tests of general relativity. We analyse the accuracy with which we can measure the masses and spins of the IMBH and its companion in intermediate-mass-ratio coalescences. We find that we can identify an IMBH with a mass above 100 M with 95 per cent confidence provided the massive body exceeds 130 M . For source masses above ~200 M , the best measured parameter is the frequency of the quasi-normal ringdown. Consequently, the total mass is measured better than the chirp mass for massive binaries, but the total mass is still partly degenerate with spin, which cannot be accurately measured. Low-frequency detector sensitivity is particularly important for massive sources, since sensitivity to the inspiral phase is critical for measuring the mass of the stellar-mass companion. We show that we can accurately infer source parameters for cosmologically redshifted signals by applying appropriate corrections. We investigate the impact of uncertainty in the model gravitational waveforms and conclude that our main results are likely robust to systematics.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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