The TAO-Gen Algorithm for Identifying Gene Interaction Networks with Application to SOS Repair in E. coli

One major unresolved issue in the analysis of gene expression data is the identification and quantification of gene regulatory networks. Several methods have been proposed for identifying gene regulatory networks, but these methods predominantly focus on the use of multiple pairwise comparisons to identify the network structure. In this article, we describe a method for analyzing gene expression data to determine a regulatory structure consistent with an observed set of expression profiles. Unlike other methods this method goes beyond pairwise evaluations by using likelihood-based statistical methods to obtain the network that is most consistent with the complete data set. The proposed algorithm performs accurately for moderate-sized networks with most errors being minor additions of linkages. However, the analysis also indicates that sample sizes may need to be increased to uniquely identify even moderate-sized networks. The method is used to evaluate interactions between genes in the SOS signaling pathway in Escherichia coli using gene expression data where each gene in the network is over-expressed using plasmids inserts

Transcriptional responses underlying the hormetic and detrimental effects of the plant secondary metabolite gossypol on the generalist herbivore Helicoverpa armigera

<p>Abstract</p> <p>Background</p> <p>Hormesis is a biphasic biological response characterized by the stimulatory effect at relatively low amounts of chemical compounds which are otherwise detrimental at higher concentrations. A hormetic response in larval growth rates has been observed in cotton-feeding insects in response to increasing concentrations of gossypol, a toxic metabolite found in the pigment glands of some plants in the family Malvaceae. We investigated the developmental effect of gossypol in the cotton bollworm, <it>Helicoverpa armigera</it>, an important heliothine pest species, by exposing larvae to different doses of this metabolite in their diet. In addition, we sought to determine the underlying transcriptional responses to different gossypol doses.</p> <p>Results</p> <p>Larval weight gain, pupal weight and larval development time were measured in feeding experiments and a hormetic response was seen for the first two characters. On the basis of net larval weight gain responses to gossypol, three concentrations (0%, 0.016% and 0.16%) were selected for transcript profiling in the gut and the rest of the body in a two-color double reference design microarray experiment. Hormesis could be observed at the transcript level, since at the low gossypol dose, genes involved in energy acquisition such as β-fructofuranosidases were up-regulated in the gut, and genes involved in cell adhesion were down-regulated in the body. Genes with products predicted to be integral to the membrane or associated with the proteasome core complex were significantly affected by the detrimental dose treatment in the body. Oxidoreductase activity-related genes were observed to be significantly altered in both tissues at the highest gossypol dose.</p> <p>Conclusions</p> <p>This study represents the first transcriptional profiling approach investigating the effects of different concentrations of gossypol in a lepidopteran species. <it>H. armigera</it>'s transcriptional response to gossypol feeding is tissue- and dose-dependent and involves diverse detoxifying mechanisms not only to alleviate direct effects of gossypol but also indirect damage such as pH disturbance and oxygen radical formation. Genes discovered through this transcriptional approach may be additional candidates for understanding gossypol detoxification and coping with gossypol-induced stress. In a generalist herbivore that has evolved transcriptionally-regulated responses to a variety of different plant compounds, hormesis may be due to a lower induction threshold of growth-promoting, stress-coping responses and a higher induction threshold of detoxification pathways that are costly and cause collateral damage to the cell.</p

G1(M) no bekutoruba to kori A

制度:新 ; 文部省報告番号:乙1532号 ; 学位の種類:博士(理学) ; 授与年月日:2000-03-02 ; 早大学位記番号:新2995 ; 理工学図書館請求番号:2493早稲田大

Thesaurus for energy and rural development

With the assistance of: Ann Jacobs, Richard Morse, Thammanun Pongsrikul, Jamuna Ramakrishna, Michael T. Santerre, Charles C. Schlegel, Kirk R. Smith. For more about the East-West Center, see http://www.eastwestcenter.org/Revised and expanded edition. Joint publication of the Energy for Rural Development (ERD) Program and the Pacific Island Energy Studies (PIES) Program at the East-West Center. East-West Resource Systems Institute. Energy Program - East-West Center. Pacific Islands Development Progra

Gene regulatory network analysis defines transcriptome landscape with alternative splicing of human umbilical vein endothelial cells during replicative senescence

Background Endothelial cell senescence is the state of permanent cell cycle arrest and plays a critical role in the pathogenesis of age-related diseases. However, a comprehensive understanding of the gene regulatory network, including genome-wide alternative splicing machinery, involved in endothelial cell senescence is lacking. Results We thoroughly described the transcriptome landscape of replicative senescent human umbilical vein endothelial cells. Genes with high connectivity showing a monotonic expression increase or decrease with the culture period were defined as hub genes in the co-expression network. Computational network analysis of these genes led to the identification of canonical and non-canonical senescence pathways, such as E2F and SIRT2 signaling, which were down-regulated in lipid metabolism, and chromosome organization processes pathways. Additionally, we showed that endothelial cell senescence involves alternative splicing. Importantly, the first and last exon types of splicing, as observed in FLT1 and ACACA, were preferentially altered among the alternatively spliced genes during endothelial senescence. We further identified novel microexons in PRUNE2 and PSAP, each containing 9 nt, which were altered within the specific domain during endothelial senescence. Conclusions These findings unveil the comprehensive transcriptome pathway and novel signaling regulated by RNA processing, including gene expression and splicing, in replicative endothelial senescence.Medicine, Faculty ofNon UBCPathology and Laboratory Medicine, Department ofReviewedFacultyResearcherOthe