SNP@Evolution: a hierarchical database of positive selection on the human genome

<p>Abstract</p> <p>Background</p> <p>Positive selection is a driving force that has shaped the modern human. Recent developments in high throughput technologies and corresponding statistics tools have made it possible to conduct whole genome surveys at a population scale, and a variety of measurements, such as heterozygosity (HET), <it>F</it>_<it>ST</it>, and Tajima's D, have been applied to multiple datasets to identify signals of positive selection. However, great effort has been required to combine various types of data from individual sources, and incompatibility among datasets has been a common problem. SNP@Evolution, a new database which integrates multiple datasets, will greatly assist future work in this area.</p> <p>Description</p> <p>As part of our research scanning for evolutionary signals in HapMap Phase II and Phase III datasets, we built SNP@Evolution as a multi-aspect database focused on positive selection. Among its many features, SNP@Evolution provides computed <it>F</it>_{<it>ST </it>}and HET of all HapMap SNPs, 5+ HapMap SNPs per qualified gene, and all autosome regions detected from whole genome window scanning. In an attempt to capture multiple selection signals across the genome, selection-signal enrichment strength (E_S) values of HET, <it>F</it>_<it>ST</it>, and <it>P</it>-values of iHS of most annotated genes have been calculated and integrated within one frame for users to search for outliers. Genes with significant E_Sor <it>P</it>-values (with thresholds of 0.95 and 0.05, respectively) have been highlighted in color. Low diversity chromosome regions have been detected by sliding a 100 kb window in a 10 kb step. To allow this information to be easily disseminated, a graphical user interface (GBrowser) was constructed with the Generic Model Organism Database toolkit.</p> <p>Conclusion</p> <p>Available at <url>http://bighapmap.big.ac.cn</url>, SNP@Evolution is a hierarchical database focused on positive selection of the human genome. Based on HapMap Phase II and III data, SNP@Evolution includes 3,619,226/1,389,498 SNPs with their computed HET and <it>F</it>_<it>ST</it>, as well as qualified genes of 21,859/21,099 with E_Svalues of HET and <it>F</it>_<it>ST</it>. In at least one HapMap population group, window scanning for selection signals has resulted in 1,606/10,138 large low HET regions. Among Phase II and III geographical groups, 660 and 464 regions show strong differentiation.</p

RNA sequencing reveals CircRNA expression profiles in chicken embryo fibroblasts infected with velogenic Newcastle disease virus

IntroductionNewcastle disease virus (NDV) is an important avian pathogen prevalent worldwide; it has an extensive host range and seriously harms the poultry industry. Velogenic NDV strains exhibit high pathogenicity and mortality in chickens. Circular RNAs (circRNAs) are among the most abundant and conserved eukaryotic transcripts. They are part of the innate immunity and antiviral response. However, the relationship between circRNAs and NDV infection is unclear.MethodsIn this study, we used circRNA transcriptome sequencing to analyze the differences in circRNA expression profiles post velogenic NDV infection in chicken embryo fibroblasts (CEFs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to reveal significant enrichment of differentially expressed (DE) circRNAs. The circRNA- miRNA-mRNA interaction networks were further predicted. Moreover, circ-EZH2 was selected to determine its effect on NDV infection in CEFs.ResultsNDV infection altered circRNA expression profiles in CEFs, and 86 significantly DE circRNAs were identified. GO and KEGG enrichment analyses revealed significant enrichment of DE circRNAs for metabolism-related pathways, such as lysine degradation, glutaminergic synapse, and alanine, aspartic-acid, and glutamic-acid metabolism. The circRNA- miRNA-mRNA interaction networks further demonstrated that CEFs might combat NDV infection by regulating metabolism through circRNA-targeted mRNAs and miRNAs. Furthermore, we verified that circ-EZH2 overexpression and knockdown inhibited and promoted NDV replication, respectively, indicating that circRNAs are involved in NDV replication.ConclusionsThese results demonstrate that CEFs exert antiviral responses by forming circRNAs, offering new insights into the mechanisms underlying NDV-host interactions

Impact of biogenic SOA loading on the molecular composition of wintertime PM2.5 in urban Tianjin: an insight from Fourier transform ion cyclotron resonance mass spectrometry

Biomass burning is one of the key sources of urban aerosols in the North China Plain, especially in winter when the impact of secondary organic aerosols (SOA) formed from biogenic volatile organic compounds (BVOCs) is generally considered to be minor. However, little is known about the influence of biogenic SOA loading on the molecular composition of wintertime organic aerosols. Here, we investigated the water-soluble organic compounds in fine particles (PM2.5) from urban Tianjin by ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Our results show that most of the CHO and CHON compounds were derived from biomass burning; they contain O-poor and highly unsaturated compounds with aromatic rings, which are sensitive to photochemical reactions, and some of which probably contribute to light-absorbing chromophores. Under moderate to high SOA loading conditions, the nocturnal chemistry is more efficient than photooxidation to generate secondary CHO and CHON compounds with high oxygen content. Under low SOA-loading, secondary CHO and CHON compounds with low oxygen content are mainly formed by photochemistry. Secondary CHO compounds are mainly derived from oxidation of monoterpenes. But nocturnal chemistry may be more productive to sesquiterpene-derived CHON compounds. In contrast, the number- and intensity-weight of S-containing groups (CHOS and CHONS) increased significantly with the increase of biogenic SOA-loading, which agrees with the fact that a majority of the S-containing groups are identified as organosulfates and nitrooxy-organosulfates that are derived from the oxidation of BVOCs. Terpenes may be potential major contributors to the chemical diversity of organosulfates and nitrooxy-organosulfates under photo-oxidation. While the nocturnal chemistry is more beneficial to the formation of organosulfates and nitrooxy-organosulfates under low SOA-loading. The SOA-loading is an important factor associating with the oxidation degree, nitrate group content and chemodiversity of nitrooxy-organosulfates. Furthermore, our study suggests that the hydrolysis of nitrooxy-organosulfates is a possible pathway for the formation of organosulfates.</p

Proceedings of the I ndo‐ U.S. bilateral workshop on accelerating botanicals/biologics agent development research for cancer chemoprevention, treatment, and survival

With the evolving evidence of the promise of botanicals/biologics for cancer chemoprevention and treatment, an Indo‐U.S. collaborative Workshop focusing on “Accelerating Botanicals Agent Development Research for Cancer Chemoprevention and Treatment” was conducted at the Moffitt Cancer Center, 29–31 May 2012. Funded by the Indo‐U.S. Science and Technology Forum, a joint initiative of Governments of India and the United States of America and the Moffitt Cancer Center, the overall goals of this workshop were to enhance the knowledge (agents, molecular targets, biomarkers, approaches, target populations, regulatory standards, priorities, resources) of a multinational, multidisciplinary team of researcher's to systematically accelerate the design, to conduct a successful clinical trials to evaluate botanicals/biologics for cancer chemoprevention and treatment, and to achieve efficient translation of these discoveries into the standards for clinical practice that will ultimately impact cancer morbidity and mortality. Expert panelists were drawn from a diverse group of stakeholders, representing the leadership from the National Cancer Institute's Office of Cancer Complementary and Alternative Medicine (OCCAM), NCI Experimental Therapeutics (NExT), Food and Drug Administration, national scientific leadership from India, and a distinguished group of population, basic and clinical scientists from the two countries, including leaders in bioinformatics, social sciences, and biostatisticians. At the end of the workshop, we established four Indo‐U.S. working research collaborative teams focused on identifying and prioritizing agents targeting four cancers that are of priority to both countries. Presented are some of the key proceedings and future goals discussed in the proceedings of this workshop. With the evolving evidence of the promise of botanicals/biologics for cancer chemoprevention and treatment, the proceedings of the Indo‐U.S. collaborative Workshop represent one of the most contemporary issues in Cancer Medicine .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96353/1/cam442.pd

Proceedings of the I ndo‐ U.S. bilateral workshop on accelerating botanicals/biologics agent development research for cancer chemoprevention, treatment, and survival

With the evolving evidence of the promise of botanicals/biologics for cancer chemoprevention and treatment, an Indo‐U.S. collaborative Workshop focusing on “Accelerating Botanicals Agent Development Research for Cancer Chemoprevention and Treatment” was conducted at the Moffitt Cancer Center, 29–31 May 2012. Funded by the Indo‐U.S. Science and Technology Forum, a joint initiative of Governments of India and the United States of America and the Moffitt Cancer Center, the overall goals of this workshop were to enhance the knowledge (agents, molecular targets, biomarkers, approaches, target populations, regulatory standards, priorities, resources) of a multinational, multidisciplinary team of researcher's to systematically accelerate the design, to conduct a successful clinical trials to evaluate botanicals/biologics for cancer chemoprevention and treatment, and to achieve efficient translation of these discoveries into the standards for clinical practice that will ultimately impact cancer morbidity and mortality. Expert panelists were drawn from a diverse group of stakeholders, representing the leadership from the National Cancer Institute's Office of Cancer Complementary and Alternative Medicine (OCCAM), NCI Experimental Therapeutics (NExT), Food and Drug Administration, national scientific leadership from India, and a distinguished group of population, basic and clinical scientists from the two countries, including leaders in bioinformatics, social sciences, and biostatisticians. At the end of the workshop, we established four Indo‐U.S. working research collaborative teams focused on identifying and prioritizing agents targeting four cancers that are of priority to both countries. Presented are some of the key proceedings and future goals discussed in the proceedings of this workshop. With the evolving evidence of the promise of botanicals/biologics for cancer chemoprevention and treatment, the proceedings of the Indo‐U.S. collaborative Workshop represent one of the most contemporary issues in Cancer Medicine .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96353/1/cam442.pd

Frequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas

The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Here we present an integrated genomic and transcriptomic analysis of 335 primary lung adenocarcinomas and 35 corresponding lymph node metastases from Chinese patients. Altogether 13 significantly mutated genes are identified, including the most commonly mutated gene TP53 and novel mutation targets such as RHPN2, GLI3 and MRC2. TP53 mutations are furthermore significantly enriched in tumours from patients harbouring metastases. Genes regulating cytoskeleton remodelling processes are also frequently altered, especially in metastatic samples, of which the high expression level of IQGAP3 is identified as a marker for poor prognosis. Our study represents the first large-scale sequencing effort on lung adenocarcinoma in Asian patients and provides a comprehensive mutational landscape for both primary and metastatic tumours. This may thus form a basis for personalized medical care and shed light on the molecular pathogenesis of metastatic lung adenocarcinoma