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  • 1
    Publication Date: 2015-06-02
    Description: Community detection in social networks is one of the most active problems with lots of applications. Most of the existing works on the problem have focused on detecting the community considering only the closeness between community members. In the real world, however, it is also important to consider bad relationships between members. In this paper, we propose a new variant of the community detection problem, called friendly community search . In the proposed problem, for a given graph, we aim to not only find a densely connected subgraph that contains a given set of query nodes but also minimizes the number of nodes involved in bad relationships in the subgraph. We prove that is Non-deterministic Polynomial-time hard (NP-hard), and develop two novel algorithms, called G reedy and S teiner S wap that return the near optimal solutions. Experimental results show that two proposed algorithms outperform the algorithm adapted from an existing algorithm for the optimal quasi-clique problem.
    Print ISSN: 0010-4620
    Electronic ISSN: 1460-2067
    Topics: Computer Science
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  • 2
    Publication Date: 2012-06-24
    Description: : The method for genome-wide association study (GWAS) based on copy number variation (CNV) is not as well established as that for single nucleotide polymorphism (SNP)–GWAS. Although there are several tools for CNV association studies, most of them do not provide appropriate definitions of CNV regions (CNVRs), which are essential for CNV-association studies. Here we present a user-friendly program called CNVRuler for CNV-association studies. Outputs from the 10 most common CNV defining algorithms can be directly used as input files for determining the three different definitions of CNVRs. Once CNVRs are defined, CNVRuler supports four kinds of statistical association tests and options for population stratification. CNVRuler is based on the open-source programs R and Java from Sun Microsystems. Availability: CNVRuler software is available with an online manual at the website, www.ircgp.com/CNVRuler/index.html Contact: yejun@catholic.ac.kr . Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 3
    Publication Date: 2014-01-11
    Description: DNA methylation and hydroxymethylation have been implicated in normal development and differentiation, but our knowledge is limited about the genome-wide distribution of 5-methylcytosine (5 mC) and 5-hydroxymethylcytosine (5 hmC) during cellular differentiation. Using an in vitro model system of gradual differentiation of human embryonic stem (hES) cells into ventral midbrain-type neural precursor cells and terminally into dopamine neurons, we observed dramatic genome-wide changes in 5 mC and 5 hmC patterns during lineage commitment. The 5 hmC pattern was dynamic in promoters, exons and enhancers. DNA hydroxymethylation within the gene body was associated with gene activation. The neurogenesis-related genes NOTCH1 , RGMA and AKT1 acquired 5 hmC in the gene body and were up-regulated during differentiation. DNA methylation in the promoter was associated with gene repression. The pluripotency-related genes POU5F1 , ZFP42 and HMGA1 acquired 5 mC in their promoters and were down-regulated during differentiation. Promoter methylation also acted as a locking mechanism to maintain gene silencing. The mesoderm development-related genes NKX2-8 , TNFSF11 and NFATC1 acquired promoter methylation during neural differentiation even though they were already silenced in hES cells. Our findings will help elucidate the molecular mechanisms underlying lineage-specific differentiation of pluripotent stem cells during human embryonic development.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 4
    Publication Date: 2014-02-28
    Description: The nucleotide excision repair pathway removes ultraviolet (UV) photoproducts from the human genome in the form of short oligonucleotides ~30 nt in length. Because there are limitations to many of the currently available methods for investigating UV photoproduct repair in vivo , we developed a convenient non-radioisotopic method to directly detect DNA excision repair events in human cells. The approach involves extraction of oligonucleotides from UV-irradiated cells, DNA end-labeling with biotin and streptavidin-mediated chemiluminescent detection of the excised UV photoproduct-containing oligonucleotides that are released from the genome during excision repair. Our novel approach is robust, with essentially no signal in the absence of UV or a functional excision repair system. Furthermore, our non-radioisotopic methodology allows for the sensitive detection of excision products within minutes following UV irradiation and does not require additional enrichment steps such as immunoprecipitation. Finally, this technique allows for quantitative measurements of excision repair in human cells. We suggest that the new techniques presented here will be a useful and powerful approach for studying the mechanism of human nucleotide excision repair in vivo .
    Keywords: Repair
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 5
    Publication Date: 2014-11-07
    Description: : Because cancer has heterogeneous clinical behaviors due to the progressive accumulation of multiple genetic and epigenetic alterations, the identification of robust molecular signatures for predicting cancer outcome is profoundly important. Here, we introduce the APPEX Web-based analysis platform as a versatile tool for identifying prognostic molecular signatures that predict cancer diversity. We incorporated most of statistical methods for survival analysis and implemented seven survival analysis workflows, including CoxSingle , CoxMulti , IntransSingle , IntransMulti , SuperPC , TimeRoc and multivariate . A total of 236 publicly available datasets were collected, processed and stored to support easy independent validation of prognostic signatures. Two case studies including disease recurrence and bladder cancer progression were described using different combinations of the seven workflows. Availability and implementation: APPEX is freely available at http://www.appex.kr . Contact: kimsy@kribb.re.kr Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 6
    Publication Date: 2015-04-02
    Description: Next-generation sequencing has been widely used for the genome-wide profiling of histone modifications, transcription factor binding and gene expression through chromatin immunoprecipitated DNA sequencing (ChIP-seq) and cDNA sequencing (RNA-seq). Here, we describe a versatile library construction method that can be applied to both ChIP-seq and RNA-seq on the widely used Illumina platforms. Standard methods for ChIP-seq library construction require nanograms of starting DNA, substantially limiting its application to rare cell types or limited clinical samples. By minimizing the DNA purification steps that cause major sample loss, our method achieved a high sensitivity in ChIP-seq library preparation. Using this method, we achieved the following: (i) generated high-quality epigenomic and transcription factor-binding maps using ChIP-seq for murine adipocytes; (ii) successfully prepared a ChIP-seq library from as little as 25 pg of starting DNA; (iii) achieved paired-end sequencing of the ChIP-seq libraries; (iv) systematically profiled gene expression dynamics during murine adipogenesis using RNA-seq and (v) preserved the strand specificity of the transcripts in RNA-seq. Given its sensitivity and versatility in both double-stranded and single-stranded DNA library construction, this method has wide applications in genomic, epigenomic, transcriptomic and interactomic studies.
    Keywords: Massively Parallel (Deep) Sequencing
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 7
    Publication Date: 2012-10-30
    Description: The effect of phospholipids on the kinetic parameters of three substrates, 7-ethoxy-4 -(trifluoromethyl)coumarin (7-EFC), 7-ethoxycoumarin (7-EC) and 17β-estradiol (E 2 ), of human CYP1B1 was studied. In general, anionic phospholipids, phosphatidic acid and cardiolipin increased catalytic efficiency by increasing k cat values or decreasing K m values. The advantages of using the 7-EFC as a substrate over 7-EC and E 2 include high k cat , low K m and high catalytic efficiency. Spectral binding titrations indicated that the binding affinity of 7-EFC to CYP1B1 in the presence or absence of phospholipids is higher than that of 7-EC or E 2 . Furthermore, phosphatidylcholine increased the binding affinity of the substrates to the CYP1B1. High non-competitive intermolecular kinetic deuterium isotope effects (values 5.4–12) were observed for O -deethylation of 7-EFC and 7-EC with deuterium substitution at the ethoxy group, indicating that the C–H bond-breaking step makes a major contribution to the rate of these CYP1B1-catalyzed reactions. However, the intermolecular kinetic deuterium isotope effect is ~2 for the E 2 4-hydroxylation reaction, indicating that the C–H bond-breaking step contributes only partially to the rate of this CYP1B1-catalyzed reaction. These results indicate that the reaction mechanism of CYP1B1-catalyzed reactions is distinct for each substrate.
    Print ISSN: 0021-924X
    Electronic ISSN: 1756-2651
    Topics: Biology , Chemistry and Pharmacology
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  • 8
    Publication Date: 2014-02-15
    Description: People and governments tend to have shorter time horizons when faced with economic uncertainty. Scientific discoveries and technological innovations requiring long-term commitment and investment are thus likely to suffer from higher rates of future discounting in times of economic insecurity. At the same time, governments are pressed for counter-cyclical measures in economic downturns, since recessions create large demands for compensatory spending for people and sectors at risk. This study explores how government investment in science and technology responds to economic downturns with a panel analysis of the data from 21 OECD nations for the period 1981–2011. Drawing on the varieties of capitalism (VoC) theory, the study explores how institutional complementarities underlying different regimes of political economy influence the downturn behavior of government-funded R&D. The empirical evidence presented here is largely supportive of the VoC conjecture, showing that government R&D funding is distinctly counter-cyclical in coordinated market economies.
    Print ISSN: 0302-3427
    Electronic ISSN: 1471-5430
    Topics: Nature of Science, Research, Systems of Higher Education, Museum Science
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  • 9
    Publication Date: 2015-01-07
    Description: Peptide: N -glycanase (PNGase) A is used preferentially to cleave the glycans from plant and insect glycopeptides. Although many putative PNGase A homologous genes have been found in the plant and fungus kingdoms through sequence similarity analyses, only several PNGases from plants and one from a filamentous fungus have been characterized. In this study, we identified and characterized a PNGase A-like enzyme, PNGase Yl, in the dimorphic yeast Yarrowia lipolytica . The corresponding gene was cloned and recombinantly expressed in Pichia pastoris . The purified enzyme cleaved glycans from glycopeptides with the maximum activity at pH 5. No metal ions were required for full activity, and rather it was repressed by three metal ions (Fe 3+ , Cu 2+ and Zn 2+ ). Using glycopeptide substrates, PNGase Yl was shown to release various types of N -glycans including high-mannose and complex-type glycans as well as glycans containing core-linked α(1,3)-fucose that are frequently found in plants and insects. Moreover, in comparison with PNGase A, PNGase Yl was able to cleave with higher efficiency the glycans from some denatured glycoproteins. Taken together, our results suggest that PNGase Yl, the first biochemically characterized yeast PNGase A homologue, can be developed through protein engineering as a useful deglycosylation tool for N -glycosylation study.
    Print ISSN: 0021-924X
    Electronic ISSN: 1756-2651
    Topics: Biology , Chemistry and Pharmacology
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  • 10
    Publication Date: 2013-02-02
    Description: MicroRNAs (miRNAs) are small regulatory RNAs that have important regulatory roles in numerous developmental and metabolic processes in most eukaryotes. In Arabidopsis , DICER-LIKE1 (DCL1), HYPONASTIC LEAVES 1, SERRATE, HUA ENHANCER1 and HASTY are involved in processing of primary miRNAs (pri-miRNAs) to yield precursor miRNAs (pre-miRNAs) and eventually miRNAs. In addition to these components, mRNA cap-binding proteins, CBP80 / ABA HYPERSENSITIVE1 and CBP20 , also participate in miRNA biogenesis. Here, we show that STABILIZED1 ( STA1 ), an Arabidopsis pre-mRNA processing factor 6 homolog, is also involved in the biogenesis of miRNAs. Similar to other miRNA biogenesis-defective mutants, sta1-1 accumulated significantly lower levels of mature miRNAs and concurrently higher levels of pri-miRNAs than wild type. The dramatic reductions of mature miRNAs were associated with the accumulation of their target gene transcripts and developmental defects. Furthermore, sta1-1 impaired splicing of intron containing pri-miRNAs and decreased transcript levels of DCL1 . These results suggest that STA1 is involved in miRNA biogenesis directly by functioning in pri-miRNA splicing and indirectly by modulating the DCL1 transcript level.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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