Metabolomics as a Hypothesis-Generating Functional Genomics Tool for the Annotation of Arabidopsis thaliana Genes of “Unknown Function”

Metabolomics is the methodology that identifies and measures global pools of small molecules (of less than about 1,000 Da) of a biological sample, which are collectively called the metabolome. Metabolomics can therefore reveal the metabolic outcome of a genetic or environmental perturbation of a metabolic regulatory network, and thus provide insights into the structure and regulation of that network. Because of the chemical complexity of the metabolome and limitations associated with individual analytical platforms for determining the metabolome, it is currently difficult to capture the complete metabolome of an organism or tissue, which is in contrast to genomics and transcriptomics. This paper describes the analysis of Arabidopsis metabolomics data sets acquired by a consortium that includes five analytical laboratories, bioinformaticists, and biostatisticians, which aims to develop and validate metabolomics as a hypothesis-generating functional genomics tool. The consortium is determining the metabolomes of Arabidopsis T-DNA mutant stocks, grown in standardized controlled environment optimized to minimize environmental impacts on the metabolomes. Metabolomics data were generated with seven analytical platforms, and the combined data is being provided to the research community to formulate initial hypotheses about genes of unknown function (GUFs). A public database (www.PlantMetabolomics.org) has been developed to provide the scientific community with access to the data along with tools to allow for its interactive analysis. Exemplary datasets are discussed to validate the approach, which illustrate how initial hypotheses can be generated from the consortium-produced metabolomics data, integrated with prior knowledge to provide a testable hypothesis concerning the functionality of GUFs

Nationalists, Communists, and rural leaders: political dynamics in a Chinese county, 1927-1937

Thesis (Ph. D.)--University of Washington, 1983During the initial years of their rule, 1927 to 1937, did the Nationalists transform the politics of rural China? Through a study of Nationalist political organization and policy implementation in one particular area of China, Rugao County, Jiangsu Province, this dissertation attempts to answer the above question. It examines the establishment of the county's Nationalist Party and government organizations, the ways in which these organizations implemented policy, and the relationships that developed between the Nationalists and other political groups, especially the Communists and indigenous rural leaders. In 1927 the Rugao branch of the Nationalist Party briefly dominated county political affairs, but thereafter, because of the centrally-directed purge of Communists from Nationalist Party ranks, drastically decreased in importance. Between 1928 and 1930 the government tried to set up an enlarged, reformed political organization in Rugao, but because of the lack of higher-level support and local opposition was unsuccessful. After 1930 the indigenous local elite, as they had before 1927, once again exercised power and authority over Rugao political affairs. While the Nationalists never formally allied with local leaders, they often relied on them to carry out government policy. As a result, during the entire Decade the only Nationalist programs that were implemented were those in which local leaders took an interest. In the end, those most often were actions needed to alleviate a crisis, such as the rise of the Communists, or a natural disaster such as flooding, drought, or the appearance of locusts. Other long-term programs, such as water conservancy projects or agricultural improvement efforts, received little attention. Consequently, Nationalist rule in Rugao during the so-called Nanjing Decade can best be characterized as punctuated crisis government, and it can be seen that because the Nationalists in Rugao did not replace the pre-existing power structure, did not set up a sizeable political organization of their own, and did not implement most of their policies, that they failed to penetrate the Rugao countryside or to change the life of Rugao's residents

PlantMetabolomics.org: A Web Portal for Plant Metabolomics Experiments1[C][W][OA]

PlantMetabolomics.org (PM) is a web portal and database for exploring, visualizing, and downloading plant metabolomics data. Widespread public access to well-annotated metabolomics datasets is essential for establishing metabolomics as a functional genomics tool. PM integrates metabolomics data generated from different analytical platforms from multiple laboratories along with the key visualization tools such as ratio and error plots. Visualization tools can quickly show how one condition compares to another and which analytical platforms show the largest changes. The database tries to capture a complete annotation of the experiment metadata along with the metabolite abundance databased on the evolving Metabolomics Standards Initiative. PM can be used as a platform for deriving hypotheses by enabling metabolomic comparisons between genetically unique Arabidopsis (Arabidopsis thaliana) populations subjected to different environmental conditions. Each metabolite is linked to relevant experimental data and information from various annotation databases. The portal also provides detailed protocols and tutorials on conducting plant metabolomics experiments to promote metabolomics in the community. PM currently houses Arabidopsis metabolomics data generated by a consortium of laboratories utilizing metabolomics to help elucidate the functions of uncharacterized genes. PM is publicly available at http://www.plantmetabolomics.org

Large-scale association analyses identify host factors influencing human gut microbiome composition

To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 x 10(-8)) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 x 10(-20)), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 x 10(-10) < P < 5 x 10(-8)) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis