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  • 1
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    Long non-coding RNA identification over mouse brain development by integrative modeling of chromatin and genomic features (2013)
    Oxford University Press
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    Publication Date: 2013-12-07
    Description: In silico prediction of genomic long non-coding RNAs (lncRNAs) is prerequisite to the construction and elucidation of non-coding regulatory network. Chromatin modifications marked by chromatin regulators are important epigenetic features, which can be captured by prevailing high-throughput approaches such as ChIP sequencing. We demonstrate that the accuracy of lncRNA predictions can be greatly improved when incorporating high-throughput chromatin modifications over mouse embryonic stem differentiation toward adult Cerebellum by logistic regression with LASSO regularization. The discriminating features include H3K9me3, H3K27ac, H3K4me1, open reading frames and several repeat elements. Importantly, chromatin information is suggested to be complementary to genomic sequence information, highlighting the importance of an integrated model. Applying integrated model, we obtain a list of putative lncRNAs based on uncharacterized fragments from transcriptome assembly. We demonstrate that the putative lncRNAs have regulatory roles in vicinity of known gene loci by expression and Gene Ontology enrichment analysis. We also show that the lncRNA expression specificity can be efficiently modeled by the chromatin data with same developmental stage. The study not only supports the biological hypothesis that chromatin can regulate expression of tissue-specific or developmental stage-specific lncRNAs but also reveals the discriminating features between lncRNA and coding genes, which would guide further lncRNA identifications and characterizations.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Improved magnetogram calibration of Solar Magnetic Field Telescope and its comparison with the Helioseismic and Magnetic Imager (2014)
    Oxford University Press
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    Publication Date: 2014-09-24
    Description: In this paper, we try to improve the magnetogram calibration method of the Solar Magnetic Field Telescope (SMFT). The improved calibration process fits the observed full Stokes information, using six points on the profile of Fe i 5324.18 Å line, and the analytical Stokes profiles under the Milne–Eddington atmosphere model, adopting the Levenberg–Marquardt least-squares fitting algorithm. In comparison with the linear calibration methods, which employs one point, there is a large difference in the strength of longitudinal field B l and transverse field B t , caused by the non-linear relationship, but the discrepancy is little in the case of inclination and azimuth. We conclude that it is better to deal with the non-linear effects in the calibration of B l and B t using six points. Moreover, in comparison with Solar Dynamics Observatory/Helioseismic and Magnetic Imager (HMI), SMFT has larger stray light and acquires less magnetic field strength. For vector magnetic fields in two sunspot regions, the magnetic field strength, inclination and azimuth angles between SMFT and HMI are roughly in agreement, with the linear fitted slopes of 0.73/0.7, 0.95/1.04 and 0.99/1.1. In the case of pores and quiet regions ( B l  〈 600 G), the fitted slopes of the longitudinal magnetic field strength are 0.78 and 0.87, respectively.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 3
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    Detrital zircon geochronology of pre-Cretaceous strata: tectonic implications for the Jiangnan Orogen, South China (2014)
    Cambridge University Press
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    Publication Date: 2014-12-04
    Description: Fifteen sandstone samples taken from pre-Cretaceous strata of the Yangtze Block are analysed to constrain the evolution of the South China Block, especially the assembly between the Yangtze and Cathaysia blocks. The results show that the maximum depositional age of the Neoproterozoic Lengjiaxi Group adjacent to the Cathaysia Block is c . 830 Ma, differing from that of the Kunyang and Dahongshan groups (〉 960 Ma) on the southwestern margin of the Yangtze Block. The detrital zircons from Palaeozoic samples from the Yangtze Block have similar age populations to those in the Cathaysia Block, and they may originate from the Cathaysia Block according to palaeogeographic, palaeocurrent and former research data. The detrital zircons of Middle–Upper Jurassic sandstones in the southwestern and central Yangtze Block yield dominant age populations at 2.0–1.7 Ga and subordinate groups of 2.6–2.4 Ga, 0.8–0.7 Ga and 0.6–0.4 Ga. The Upper Triassic strata may be derived from the southern Yangtze and North China blocks due to the collisions between the Indosina, South China and North China blocks, whereas the Jurassic sediments may be partly derived from uplift and erosion of the Jiangnan Orogen due to an intracontinental orogeny induced by Pacific subduction towards the Eurasia Plate. The detrital age spectra and provenance data for basement in the South China Block are analysed and compared with each other. The South China Block has affinity with Australia not only in the Columbia supercontinent but also in the Rodinia supercontinent. We infer the existence of an ancient orogen under the western Jiangnan Orogen, which may have occurred during the Columbia age, earlier than the Sibao orogeny. This is supported by seismic profile proof from the SinoProbe.
    Print ISSN: 0016-7568
    Electronic ISSN: 1469-5081
    Topics: Geosciences
    Published by Cambridge University Press
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  • 4
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    Revealing the architecture of genetic and epigenetic regulation: a maximum likelihood model (2014)
    Oxford University Press
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    Publication Date: 2014-11-20
    Description: Gene expression is modulated by multiple mechanisms, including genetic and/or epigenetic regulation, and associated with the processes of cellular differentiation and morphogenesis. Single nucleotide polymorphisms (SNPs) and DNA methylation play important roles in regulating gene expression. In this study, we focused on revealing the relationship between SNPs, DNA methylation and gene expression in two human populations genome-wide through proposing four regulation patterns and developed maximum likelihood estimate models. Using simulated data with different correlation coefficients between any two traits, the power of our approach showed a favourable performance and relative stability. In all, 6733 SNP–CpG-gene pairs including 957 genes were obtained in Northern European ancestry (CEU) population. As the results showed, SNPs and DNA methylation had approximately the same effect on expression regulation of 49% genes, which was termed cooperative/antagonistic regulation pattern. Less than 30% of genes are controlled only by one of the factors (SNP/DNA methylation). The others showed SNPs that affect methylation have no consequent effects or crosstalk regulation on gene expression. Similar result was shown in Yourba (YRI) population. Specific genes were inferred using the different mechanisms of gene regulation involved in complex diseases by combining literature. This approach provides a method to comprehensively assess regulation patterns of gene expression in the whole genome.
    Print ISSN: 1467-5463
    Electronic ISSN: 1477-4054
    Topics: Biology , Computer Science
    Published by Oxford University Press
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  • 5
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    TCF7L2 is a master regulator of insulin production and processing (2014)
    Oxford University Press
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    Publication Date: 2014-11-21
    Description: Genome-wide association studies have revealed 〉60 loci associated with type 2 diabetes (T2D), but the underlying causal variants and functional mechanisms remain largely elusive. Although variants in TCF7L2 confer the strongest risk of T2D among common variants by presumed effects on islet function, the molecular mechanisms are not yet well understood. Using RNA-sequencing, we have identified a TCF7L2-regulated transcriptional network responsible for its effect on insulin secretion in rodent and human pancreatic islets. ISL1 is a primary target of TCF7L2 and regulates proinsulin production and processing via MAFA , PDX1 , NKX6.1 , PCSK1 , PCSK2 and SLC30A8 , thereby providing evidence for a coordinated regulation of insulin production and processing. The risk T-allele of rs7903146 was associated with increased TCF7L2 expression, and decreased insulin content and secretion. Using gene expression profiles of 66 human pancreatic islets donors’, we also show that the identified TCF7L2-ISL1 transcriptional network is regulated in a genotype-dependent manner. Taken together, these results demonstrate that not only synthesis of proinsulin is regulated by TCF7L2 but also processing and possibly clearance of proinsulin and insulin. These multiple targets in key pathways may explain why TCF7L2 has emerged as the gene showing one of the strongest associations with T2D.
    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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    Reduction of AUF1-mediated follistatin mRNA decay during glucose starvation protects cells from apoptosis (2014)
    Oxford University Press
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    Publication Date: 2014-09-17
    Description: Follistatin (FST) performs several vital functions in the cells, including protection from apoptosis during stress. The expression of FST is up-regulated in response to glucose deprivation by an unknown mechanism. We herein showed that the induction of FST by glucose deprivation was due to an increase in the half-life of its mRNA. We further identified an AU-rich element (ARE) in the 3'UTR of FST mRNA that mediated its decay. The expression of FST was elevated after knocking down AUF1 and reduced when AUF1 was further expressed. In vitro binding assays and RNA pull-down assays revealed that AUF1 interacted with FST mRNA directly via its ARE. During glucose deprivation, a majority of AUF1 shuttled from cytoplasm to nucleus, resulting in dissociation of AUF1 from FST mRNA and thus stabilization of FST mRNA. Finally, knockdown of AUF1 decreased whereas overexpression of AUF1 increased glucose deprivation-induced apoptosis. The apoptosis promoting effect of AUF1 was eliminated in FST expressing cells. Collectively, this study provided evidence that AUF1 is a negative regulator of FST expression and participates in the regulation of cell survival under glucose deprivation.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 7
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    Characterization of p38 MAPK isoforms for drug resistance study using systems biology approach (2014)
    Oxford University Press
    Details
    Publication Date: 2014-06-27
    Description: Motivation: p38 mitogen-activated protein kinase activation plays an important role in resistance to chemotherapeutic cytotoxic drugs in treating multiple myeloma (MM). However, how the p38 mitogen-activated protein kinase signaling pathway is involved in drug resistance, in particular the roles that the various p38 isoforms play, remains largely unknown. Method: To explore the underlying mechanisms, we developed a novel systems biology approach by integrating liquid chromatography–mass spectrometry and reverse phase protein array data from human MM cell lines with computational pathway models in which the unknown parameters were inferred using a proposed novel algorithm called modularized factor graph. Results: New mechanisms predicted by our models suggest that combined activation of various p38 isoforms may result in drug resistance in MM via regulating the related pathways including extracellular signal-regulated kinase (ERK) pathway and NFB pathway. ERK pathway regulating cell growth is synergistically regulated by p38 isoform, whereas nuclear factor kappa B (NFB) pathway regulating cell apoptosis is synergistically regulated by p38α isoform. This finding that p38 isoform promotes the phosphorylation of ERK1/2 in MM cells treated with bortezomib was validated by western blotting. Based on the predicted mechanisms, we further screened drug combinations in silico and found that a promising drug combination targeting ERK1/2 and NFB might reduce the effects of drug resistance in MM cells. This study provides a framework of a systems biology approach to studying drug resistance and drug combination selection. Availability and implementation: RPPA experimental Data and Matlab source codes of modularized factor graph for parameter estimation are freely available online at http://ctsb.is.wfubmc.edu/publications/modularized-factor-graph.php Contact: xizhou@wakehealth.edu or zhanglcq@swu.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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  • 8
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    Asteroseismology of the ZZ Ceti star KUV 11370+4222 (2013)
    Oxford University Press
    Details
    Publication Date: 2013-12-23
    Description: KUV 11370+4222 is a ZZ Ceti star discovered in 1996, which has not been observed since then. We performed observations for KUV 11370+4222 in 2010 January. From the Fourier transform spectrum of the light curves, 10 independent modes are detected. We searched for the best-fitting model by using the observed periods to match the model periods and obtained it with the total mass of 0.625 M , the effective temperature of 10 950 K, and the helium mass fraction and hydrogen mass fraction of 10 –2.2 and 10 –4.0 , respectively. We have found a triplet of frequency split by rotation, which are l  = 1 modes. Using the frequency shifts, we estimate a rotation period of 5.56 ± 0.08 h. Besides it, another l  = 1 mode is identified. The other observed periods are identified as l  = 2 modes. At last we investigated the property of the mode trapping.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 9
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    Revealing the architecture of genetic and epigenetic regulation: a maximum likelihood model (2013)
    Oxford University Press
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    Publication Date: 2013-10-30
    Print ISSN: 1467-5463
    Electronic ISSN: 1477-4054
    Topics: Biology , Computer Science
    Published by Oxford University Press
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  • 10
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    DiseaseMeth: a human disease methylation database (2011)
    Oxford University Press
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    Publication Date: 2011-12-01
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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