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  • Oxford University Press  (419)
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  • 1
    Publication Date: 2014-01-28
    Description: Rhodococcus opacus strain PD630 ( R. opacus PD630), is an oleaginous bacterium, and also is one of few prokaryotic organisms that contain lipid droplets (LDs). LD is an important organelle for lipid storage but also intercellular communication regarding energy metabolism, and yet is a poorly understood cellular organelle. To understand the dynamics of LD using a simple model organism, we conducted a series of comprehensive omics studies of R. opacus PD630 including complete genome, transcriptome and proteome analysis. The genome of R. opacus PD630 encodes 8947 genes that are significantly enriched in the lipid transport, synthesis and metabolic, indicating a super ability of carbon source biosynthesis and catabolism. The comparative transcriptome analysis from three culture conditions revealed the landscape of gene-altered expressions responsible for lipid accumulation. The LD proteomes further identified the proteins that mediate lipid synthesis, storage and other biological functions. Integrating these three omics uncovered 177 proteins that may be involved in lipid metabolism and LD dynamics. A LD structure-like protein LPD06283 was further verified to affect the LD morphology. Our omics studies provide not only a first integrated omics study of prokaryotic LD organelle, but also a systematic platform for facilitating further prokaryotic LD research and biofuel development.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 2
    Publication Date: 2015-04-21
    Description: PIWI-interacting RNA (piRNA) silences the transposons in germlines or induces epigenetic modifications in the invertebrates. However, its function in the mammalian somatic cells remains unknown. Here we demonstrate that a piRNA derived from Growth Arrest Specific 5, a tumor-suppressive long non-coding RNA, potently upregulates the transcription of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a proapoptotic protein, by inducing H3K4 methylation/H3K27 demethylation. Interestingly, the PIWIL1/4 proteins, which bind with this piRNA, directly interact with WDR5, resulting in a site-specific recruitment of the hCOMPASS-like complexes containing at least MLL3 and UTX (KDM6A). We have indicated a novel pathway for piRNAs to specially activate gene expression. Given that MLL3 or UTX are frequently mutated in various tumors, the piRNA/MLL3/UTX complex mediates the induction of TRAIL, and consequently leads to the inhibition of tumor growth.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 3
    Publication Date: 2016-04-22
    Description: Skin lightening among Eurasians is thought to have been a convergence occurring independently in Europe and East Asia as an adaptation to high latitude environments. Among Europeans, several genes responsible for such lightening have been found, but the information available for East Asians is much more limited. Here, a genome-wide comparison between dark-skinned Africans and Austro-Asiatic speaking aborigines and light-skinned northern Han Chinese identified the pigmentation gene OCA2 , showing unusually deep allelic divergence between these groups. An amino acid substitution (His615Arg) of OCA2 prevalent in most East Asian populations—but absent in Africans and Europeans—was significantly associated with skin lightening among northern Han Chinese. Further transgenic and targeted gene modification analyses of zebrafish and mouse both exhibited the phenotypic effect of the OCA2 variant manifesting decreased melanin production. These results indicate that OCA2 plays an important role in the convergent skin lightening of East Asians during recent human evolution.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
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  • 4
    Publication Date: 2016-07-16
    Description: Identification of drug–target interactions is an important process in drug discovery. Although high-throughput screening and other biological assays are becoming available, experimental methods for drug–target interaction identification remain to be extremely costly, time-consuming and challenging even nowadays. Therefore, various computational models have been developed to predict potential drug–target associations on a large scale. In this review, databases and web servers involved in drug–target identification and drug discovery are summarized. In addition, we mainly introduced some state-of-the-art computational models for drug–target interactions prediction, including network-based method, machine learning-based method and so on. Specially, for the machine learning-based method, much attention was paid to supervised and semi-supervised models, which have essential difference in the adoption of negative samples. Although significant improvements for drug–target interaction prediction have been obtained by many effective computational models, both network-based and machine learning-based methods have their disadvantages, respectively. Furthermore, we discuss the future directions of the network-based drug discovery and network approach for personalized drug discovery based on personalized medicine, genome sequencing, tumor clone-based network and cancer hallmark-based network. Finally, we discussed the new evaluation validation framework and the formulation of drug–target interactions prediction problem by more realistic regression formulation based on quantitative bioactivity data.
    Print ISSN: 1467-5463
    Electronic ISSN: 1477-4054
    Topics: Biology , Computer Science
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  • 5
    Publication Date: 2014-12-01
    Description: Hirsutella minnesotensis [Ophiocordycipitaceae (Hypocreales, Ascomycota)] is a dominant endoparasitic fungus by using conidia that adhere to and penetrate the secondary stage juveniles of soybean cyst nematode. Its genome was de novo sequenced and compared with five entomopathogenic fungi in the Hypocreales and three nematode-trapping fungi in the Orbiliales (Ascomycota). The genome of H. minnesotensis is 51.4 Mb and encodes 12,702 genes enriched with transposable elements up to 32%. Phylogenomic analysis revealed that H. minnesotensis was diverged from entomopathogenic fungi in Hypocreales. Genome of H. minnesotensis is similar to those of entomopathogenic fungi to have fewer genes encoding lectins for adhesion and glycoside hydrolases for cellulose degradation, but is different from those of nematode-trapping fungi to possess more genes for protein degradation, signal transduction, and secondary metabolism. Those results indicate that H. minnesotensis has evolved different mechanism for nematode endoparasitism compared with nematode-trapping fungi. Transcriptomics analyses for the time-scale parasitism revealed the upregulations of lectins, secreted proteases and the genes for biosynthesis of secondary metabolites that could be putatively involved in host surface adhesion, cuticle degradation, and host manipulation. Genome and transcriptome analyses provided comprehensive understanding of the evolution and lifestyle of nematode endoparasitism.
    Electronic ISSN: 1759-6653
    Topics: Biology
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  • 6
    Publication Date: 2015-09-11
    Description: Motivation: The development of high-throughput sequencing technology has made it possible for more and more researchers to use population sequencing data to mine genes associated with specific traits. However, the massive amounts of sequencing data have also brought new challenges to the researchers. The question of how to browse population genomic data in an easy and intuitive manner must be addressed. Web-based genome browsers allow user to conveniently view the results of genomic analyses, but heavy usage can reduce the response speed of the webpage, which limits its usefulness in the display of large-scale genome data. IndexedDB technology is a good solution to this problem; it supports web browsers and so creates local databases. In this way, data can be read from the local storage, achieving a smooth display of population genomic data. Results: PopGeV has the following characteristics. First, it uses a new encoding method for compression of population SNP and INDEL data. IndexedDB technology is used to download the results to local storage so that users can browse the results smoothly even when the network traffic is heavy. Second, PopGeV identify similar genomic regions between two individuals based on SNP data. Population diversity indexes are calculated when comparing two populations. Third, user defined annotation information can be integrated for user-friendly mining of gene functions. Simulation shows that PopGeV can smoothly display analysis results of population genome containing over 500 individuals with 2 millions SNP data. Availability and implementation: PopGeV is available at www.soyomics.com/popgev/ Contact: yuanxh@iga.ac.cn
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 7
    Publication Date: 2015-05-21
    Description: Aims The plasticity of ecosystem responses could buffer and postpone the effects of climates on ecosystem carbon fluxes, but this lagged effect is often ignored. In this study, we used carbon flux data collected from three typical grassland ecosystems in China, including a temperate semiarid steppe in Inner Mongolia (Neimeng site, NM), an alpine shrub-meadow in Qinghai (Haibei site, HB) and an alpine meadow steppe in Tibet (Dangxiong site, DX), to examine the time lagged effects of environmental factors on CO 2 exchange. Methods Eddy covariance data were collected from three typical Chinese grasslands. In linking carbon fluxes with climatic factors, we used their averages or cumulative values within each 12-month period and we called them ‘yearly’ statistics in this study. To investigate the lagged effects of the climatic factors on the carbon fluxes, the climatic ‘yearly’ statistics were kept still and the ‘yearly’ statistics of the carbon fluxes were shifted backward 1 month at a time. Important Findings Soil moisture and precipitation was the main factor driving the annual variations of carbon fluxes at the alpine HB and DX, respectively, while the NM site was under a synthetic impact of each climatic factor. The time lagged effect analysis showed that temperature had several months, even half a year lag effects on CO 2 exchange at the three studied sites, while moisture’s effects were mostly exhibited as an immediate manner, except at NM. In general, the lagged climatic effects were relatively weak for the alpine ecosystem. Our results implied that it might be months or even 1 year before the variations of ecosystem carbon fluxes are adjusted to the current climate, so such lag effects could be resistant to more frequent climate extremes and should be a critical component to be considered in evaluating ecosystem stability. An improved knowledge on the lag effects could advance our understanding on the driving mechanisms of climate change effects on ecosystem carbon fluxes.
    Print ISSN: 1752-993X
    Electronic ISSN: 1752-9921
    Topics: Biology
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  • 8
    Publication Date: 2012-04-08
    Description: Motivation: The compound identification in gas chromatography–mass spectrometry (GC–MS) is achieved by matching the experimental mass spectrum to the mass spectra in a spectral library. It is known that the intensities with higher m / z value in the GC–MS mass spectrum are the most diagnostic. Therefore, to increase the relative significance of peak intensities of higher m / z value, the intensities and m / z values are usually transformed with a set of weight factors. A poor quality of weight factors can significantly decrease the accuracy of compound identification. With the significant enrichment of the mass spectral database and the broad application of GC–MS, it is important to re-visit the methods of discovering the optimal weight factors for high confident compound identification. Results: We developed a novel approach to finding the optimal weight factors only through a reference library for high accuracy compound identification. The developed approach first calculates the ratio of skewness to kurtosis of the mass spectral similarity scores among spectra (compounds) in a reference library and then considers a weight factor with the maximum ratio as the optimal weight factor. We examined our approach by comparing the accuracy of compound identification using the mass spectral library maintained by the National Institute of Standards and Technology. The results demonstrate that the optimal weight factors for fragment ion peak intensity and m / z value found by the developed approach outperform the current weight factors for compound identification. Availability: The results and R package are available at http://stage.louisville.edu/faculty/x0zhan17/software/ software-development . Contact: s0kim023@louisville.edu ; xiang.zhang@louisville.edu 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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  • 9
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    Oxford University Press
    Publication Date: 2014-03-19
    Description: :  With the advances of RNA sequencing technologies, scientists need new tools to analyze transcriptome data. We introduce RNAseqViewer, a new visualization tool dedicated to RNA-Seq data. The program offers innovative ways to represent transcriptome data for single or multiple samples. It is a handy tool for scientists who use RNA-Seq data to compare multiple transcriptomes, for example, to compare gene expression and alternative splicing of cancer samples or of different development stages. Availability and implementation:  RNAseqViewer is freely available for academic use at http://bioinfo.au.tsinghua.edu.cn/software/RNAseqViewer/ Contact:   zhangxg@tsinghua.edu.cn 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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  • 10
    Publication Date: 2016-04-22
    Description: Although population genetics studies have significantly accelerated the evolutionary and functional interrogations of genes and regulations, limited polymorphism data are available for rhesus macaque, the model animal closely related to human. Here, we report the first genome-wide effort to identify and visualize the population genetics profile in rhesus macaque. On the basis of the whole-genome sequencing of 31 independent macaque animals, we profiled a comprehensive polymorphism map with 46,146,548 sites. The allele frequency for each polymorphism site, the haplotype structure, as well as multiple population genetics parameters were then calculated on a genome-wide scale. We further developed a specific interface, the RhesusBase PopGateway, to facilitate the visualization of these annotations, and highlighted the applications of this highly integrative platform in clarifying the selection signatures of genes and regulations in the context of the primate evolution. Overall, the updated RhesusBase provides a comprehensive monkey population genetics framework for in-depth evolutionary studies of human biology.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
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