Improving gene-set enrichment analysis of RNA-Seq data with small replicates

Deregulated pathways identified from transcriptome data of two sample groups have played a key role in many genomic studies. Gene-set enrichment analysis (GSEA) has been commonly used for pathway or functional analysis of microarray data, and it is also being applied to RNA-seq data. However, most RNA-seq data so far have only small replicates. This enforces to apply the gene-permuting GSEA method (or preranked GSEA) which results in a great number of false positives due to the inter-gene correlation in each gene-set. We demonstrate that incorporating the absolute gene statistic in one-tailed GSEA considerably improves the false-positive control and the overall discriminatory ability of the gene-permuting GSEA methods for RNA-seq data. To test the performance, a simulation method to generate correlated read counts within a gene-set was newly developed, and a dozen of currently available RNA-seq enrichment analysis methods were compared, where the proposed methods outperformed others that do not account for the inter-gene correlation. Analysis of real RNA-seq data also supported the proposed methods in terms of false positive control, ranks of true positives and biological relevance. An efficient R package (AbsFilterG- SEA) coded with C++ (Rcpp) is available from CRAN.open

The bornavirus-derived human protein EBLN1 promotes efficient cell cycle transit, microtubule organisation and genome stability.

It was recently discovered that vertebrate genomes contain multiple endogenised nucleotide sequences derived from the non-retroviral RNA bornavirus. Strikingly, some of these elements have been evolutionary maintained as open reading frames in host genomes for over 40 million years, suggesting that some endogenised bornavirus-derived elements (EBL) might encode functional proteins. EBLN1 is one such element established through endogenisation of the bornavirus N gene (BDV N). Here, we functionally characterise human EBLN1 as a novel regulator of genome stability. Cells depleted of human EBLN1 accumulate DNA damage both under non-stressed conditions and following exogenously induced DNA damage. EBLN1-depleted cells also exhibit cell cycle abnormalities and defects in microtubule organisation as well as premature centrosome splitting, which we attribute in part, to improper localisation of the nuclear envelope protein TPR. Our data therefore reveal that human EBLN1 possesses important cellular functions within human cells, and suggest that other EBLs present within vertebrate genomes may also possess important cellular functions

Back reaction, covariant anomaly and effective action

In the presence of back reaction, we first produce the one-loop corrections for the event horizon and Hawking temperature of the Reissner-Nordstr\"om black hole. Then, based on the covariant anomaly cancelation method and the effective action technique, the modified expressions for the fluxes of gauge current and energy momentum tensor, due to the effect of back reaction, are obtained. The results are consistent with the Hawking fluxes of a (1+1)-dimensional blackbody at the temperature with quantum corrections, thus confirming the robustness of the covariant anomaly cancelation method and the effective action technique for black holes with back reaction.Comment: 17 page

Soil mobility of surface applied polyaromatic hydrocarbons in response to simulated rainfall

Polyaromatic hydrocarbons (PAHs) are emitted from a variety of sources and can accumulate on and within surface soil layers. To investigate the level of potential risk posed by surface contaminated soils, vertical soil column experiments were conducted to assess the mobility, when leached with simulated rainwater, of six selected PAHs (naphthalene, phenanthrene, fluoranthene, pyrene, benzo(e)pyrene and benzo(ghi)perylene) with contrasting hydrophobic characteristics and molecular weights/sizes. The only PAH found in the leachate within the experimental period of 26 days was naphthalene. The lack of migration of the other applied PAHs were consistent with their low mobilities within the soil columns which generally parallelled their log Koc values. Thus only 2.3% of fluoranthene, 1.8% of pyrene, 0.2% of benzo(e)pyrene and 0.4% of benzo(ghi)perylene were translocated below the surface layer. The PAH distributions in the soil columns followed decreasing power relationships with 90% reductions in the starting levels being shown to occur within a maximum average depth of 0.94 cm compared to an average starting depth of 0.5 cm. A simple predictive model identifies the extensive time periods, in excess of 10 years, required to mobilise 50% of the benzo(e)pyrene and benzo(ghi)perylene from the surface soil layer. Although this reduces to between 2 and 7 years for fluoranthene and pyrene, it is concluded that the possibility of surface applied PAHs reaching and contaminating a groundwater aquifer is unlikely

Intravenous leiomyomatosis of the uterus with extension to the right heart

A 42-year-old woman admitted with debilitation and engorgement both lower extremities. Transthoracic two-dimensional echocardiography, abdominal ultrasound and computerized tomography revealed a lobulated pelvic mass, a mass within right internal iliac vein, both common iliac vein, as well as the inferior vena cava, extending into the right atrium. In addition, echocardiography and abdominal ultrasound showed the tumor of right atrium and inferior vena cave has no stalk and has well-demarcated borders with the wall of right atrium and inferior vena cave. Hence, the presumptive diagnosis of IVL was made by echocardiography and abdominal ultrasound and the presumptive diagnosis of sarcoma with invasion in right internal iliac vein, both common iliac vein, the inferior vena cava, as well as the right atrium was made by multi-detector-row computerized tomography. The patient underwent a one-stage combined multidisciplinary thoraco-abdominal operation under general anaesthetic. Subsequently the pathologic report confirmed IVL

Causes of death and demographic characteristics of victims of meteorological disasters in Korea from 1990 to 2008

<p>Abstract</p> <p>Background</p> <p>Meteorological disasters are an important component when considering climate change issues that impact morbidity and mortality rates. However, there are few epidemiological studies assessing the causes and characteristics of deaths from meteorological disasters. The present study aimed to analyze the causes of death associated with meteorological disasters in Korea, as well as demographic and geographic vulnerabilities and their changing trends, to establish effective measures for the adaptation to meteorological disasters.</p> <p>Methods</p> <p>Deaths associated with meteorological disasters were examined from 2,045 cases in Victim Survey Reports prepared by 16 local governments from 1990 to 2008. Specific causes of death were categorized as drowning, structural collapse, electrocution, lightning, fall, collision, landslide, avalanche, deterioration of disease by disaster, and others. Death rates were analyzed according to the meteorological type, specific causes of death, and demographic and geographic characteristics.</p> <p>Results</p> <p>Drowning (60.3%) caused the greatest number of deaths in total, followed by landslide (19.7%) and structural collapse (10.1%). However, the causes of deaths differed between disaster types. The meteorological disaster associated with the greatest number of deaths has changed from flood to typhoon. Factors that raised vulnerability included living in coastal provinces (11.3 times higher than inland metropolitan), male gender (1.9 times higher than female), and older age.</p> <p>Conclusions</p> <p>Epidemiological analyses of the causes of death and vulnerability associated with meteorological disasters can provide the necessary information for establishing future adaptation measures against climate change. A more comprehensive system for assessing disaster epidemiology needs to be established.</p

Dynamics of Endoreplication during Drosophila Posterior Scutellar Macrochaete Development

Endoreplication is a variant type of DNA replication, consisting only of alternating G1 and S phases. Many types of Drosophila tissues undergo endoreplication. However, the timing and the extent to which a single endocycling macrochaete undergoes temporally programmed endoreplication during development are unclear. Here, we focused on the dynamics of endoreplication during posterior scutellar (pSC) macrochaete development. Quantitative analyses of C values in shaft cells and socket cells revealed a gradual rise from 8C and 4C at 8 hours after pupal formation (APF) to 72C and 24C at 29 hours APF, respectively. The validity of the values was further confirmed by the measurement of DNA content with a confocal laser microscope. BrdU incorporation assays demonstrated that shaft cells undergo four rounds of endoreplication from 18 to 29.5 hours APF. In contrast, socket cells undergo two rounds of endoreplication during the same period. Statistical analyses showed that the theoretical C values, based on BrdU assays, nearly coincide with the actually measured C values in socket cells, but not in shaft cells after 22 hours APF. These analyses suggest that socket cells undergo two rounds of endoreplication. However, the mechanism of endoreplication in the shaft cells may change from 22 hours APF, suggesting the possibility that shaft cells undergo two or four rounds of endoreplication during the periods. We also found that the timing of endoreplication differs, depending on the type of macrochaete. Moreover, endocycling in shaft cells of both the left and right sides of pSC bristle lineages occurs in the same pattern, indicating that the process is synchronized for specific types of macrochaete. Our findings suggest that endocycling in macrochaete cell lineages can be a model for understanding mechanisms of endoreplication at the single-cell level

Infant growth disparity in the Khanh Hoa province in Vietnam: a follow-up study

<p>Abstract</p> <p>Background</p> <p>Surveys in Vietnam have indicated that wasting and stunting have been prevalent among children, but the country is undergoing rapid socio-economic changes and little has been known about the relative situation in the different areas of the country. In 2006, the WHO introduced new growth standards applicable to all infant and child populations, which facilitates for improved assessments of the prevalence of growth impairment, independent of time, place and ethnicity. The aim of our study was to assess the growth of singleton infants delivered at term in three main birth clinics in the Khanh Hoa province in Vietnam by using the new WHO standards as reference, and the association between growth and some maternal, birth and health factors.</p> <p>Methods</p> <p>A cohort of 237 singleton infants born in the period May-July 2005 in three main delivery clinics in the Khanh Hoa province were observed prospectively. Their anthropometrical measures a year later were compared to the WHO sex-specific growth standards for weight-for-age, length-for-age, weight-for-length, and BMI-for-age. These measures were analysed as dependent outcomes using multiple linear regression models including the following independent factors: urban vs. rural birth, 1-minute Apgar score, weight and length at birth, duration of lactation, ever had diarrhoea, dengue fever, pneumonia or dysentery, and maternal age, height, gestational duration and parity.</p> <p>Results</p> <p>Compared to the standard distributions, 79% were below the median for weight-for-length; 18.0% were within the 5^thpercentile for length-for-age, 9.6% for weight-for-age, 20.3% for weight-for-length, and 19.8% for BMI. A lower length- and weight-for-age were statistically associated with being born rurally.</p> <p>Conclusions</p> <p>In this delivery-clinic based sample of children in the Khanh Hoa province in Vietnam, the proportions within the WHO-standard 5^thpercentiles for length-for-age, weight-for-length and BMI in late infancy were 3-4 times higher than expected, which indicate that deficient growth is prevalent. The infants born in a rural area had a lower weight- and length-for-age than their urban counterparts, independent of diarrhoea.</p

Gene dispersion is the key determinant of the read count bias in differential expression analysis of RNA-seq data

Background: In differential expression analysis of RNA-sequencing (RNA-seq) read count data for two sample groups, it is known that highly expressed genes (or longer genes) are more likely to be differentially expressed which is called read count bias (or gene length bias). This bias had great effect on the downstream Gene Ontology over-representation analysis. However, such a bias has not been systematically analyzed for different replicate types of RNA-seq data. Results: We show that the dispersion coefficient of a gene in the negative binomial modeling of read counts is the critical determinant of the read count bias (and gene length bias) by mathematical inference and tests for a number of simulated and real RNA-seq datasets. We demonstrate that the read count bias is mostly confined to data with small gene dispersions (e.g., technical replicates and some of genetically identical replicates such as cell lines or inbred animals), and many biological replicate data from unrelated samples do not suffer from such a bias except for genes with some small counts. It is also shown that the sample-permuting GSEA method yields a considerable number of false positives caused by the read count bias, while the preranked method does not. Conclusion: We showed the small gene variance (similarly, dispersion) is the main cause of read count bias (and gene length bias) for the first time and analyzed the read count bias for different replicate types of RNA-seq data and its effect on gene-set enrichment analysis

Wound contraction effects and antibacterial properties of Tualang honey on full-thickness burn wounds in rats in comparison to hydrofibre

<p>Abstract</p> <p>Background</p> <p>Full-thickness burn wounds require excision and skin grafting. Multiple surgical procedures are inevitable in managing moderate to severe full-thickness burns. Wound bed preparations prior to surgery are necessary in order to prevent wound infection and promote wound healing. Honey can be used to treat burn wounds. However, not all the honey is the same. This study aims to evaluate the wound contraction and antibacterial properties of locally-produced <it>Tualang </it>honey on managing full-thickness burn wounds <it>in vivo</it>.</p> <p>Methods</p> <p>Thirty-six female <it>Sprague Dawley </it>rats were randomly divided into three groups. Under anaesthesia, three full-thickness burn wounds were created on the dorsum of the rats. The full-thickness burn wounds were inoculated with a specific organism (10⁴), namely <it>Pseudomonas aeruginosa </it>(n = 12), <it>Klebsiella pneumoniae </it>(n = 12), or <it>Acinetobacter baumannii </it>(n = 12). The three burn wounds were dressed with <it>Tualang </it>honey, hydrofibre and hydrofibre silver respectively. Swab samples were obtained every 3 days (day 3, 6, 9, 12, 15, 18 and 21) for quantitative and semi-quantitative microbiological analyses. Clinical assessments, including observations concerning the appearance and wound size, were measured at the same time.</p> <p>Results</p> <p>There was a rapid 32.26% reduction in wound size by day 6 (<it>p </it>= 0.008) in the <it>Tualang </it>honey-treated wounds, and 49.27% by day 15 (<it>p </it>= 0.005). The wounds remained smaller by day 18 (<it>p </it>< 0.032). <it>Tualang </it>honey-treated rats demonstrated a reduction in bacterial growth in <it>Pseudomonas aeruginosa </it>inoculated wounds (<it>p </it>= 0.005). However, hydrofibre silver and hydrofibre-treated wounds are superior to honey-treated wounds with <it>Acinetobacter baumannii </it>(<it>p </it>= 0.035). There was no statistical significant of antibacterial property in <it>Klebsiella pneumonia </it>inoculated wounds.</p> <p>Conclusions</p> <p><it>Tualang </it>honey has better results with regards to its control of <it>Pseudomonas aeruginosa </it>and its wound contraction effects on full-thickness burn wound <it>in vivo</it>.</p