Genome comparison using Gene Ontology (GO) with statistical testing

BACKGROUND: Automated comparison of complete sets of genes encoded in two genomes can provide insight on the genetic basis of differences in biological traits between species. Gene ontology (GO) is used as a common vocabulary to annotate genes for comparison. Current approaches calculate the fold of unweighted or weighted differences between two species at the high-level GO functional categories. However, to ensure the reliability of the differences detected, it is important to evaluate their statistical significance. It is also useful to search for differences at all levels of GO. RESULTS: We propose a statistical approach to find reliable differences between the complete sets of genes encoded in two genomes at all levels of GO. The genes are first assigned GO terms from BLAST searches against genes with known GO assignments, and for each GO term the abundance of genes in the two genomes is compared using a chi-squared test followed by false discovery rate (FDR) correction. We applied this method to find statistically significant differences between two cyanobacteria, Synechocystis sp. PCC6803 and Anabaena sp. PCC7120. We then studied how the set of identified differences vary when different BLAST cutoffs are used. We also studied how the results vary when only subsets of the genes were used in the comparison of human vs. mouse and that of Saccharomyces cerevisiae vs. Schizosaccharomyces pombe. CONCLUSION: There is a surprising lack of statistical approaches for comparing complete genomes at all levels of GO. With the rapid increase of the number of sequenced genomes, we hope that the approach we proposed and tested can make valuable contribution to comparative genomics

Genes and (Common) Pathways Underlying Drug Addiction

Drug addiction is a serious worldwide problem with strong genetic and environmental influences. Different technologies have revealed a variety of genes and pathways underlying addiction; however, each individual technology can be biased and incomplete. We integrated 2,343 items of evidence from peer-reviewed publications between 1976 and 2006 linking genes and chromosome regions to addiction by single-gene strategies, microrray, proteomics, or genetic studies. We identified 1,500 human addiction-related genes and developed KARG (http://karg.cbi.pku.edu.cn), the first molecular database for addiction-related genes with extensive annotations and a friendly Web interface. We then performed a meta-analysis of 396 genes that were supported by two or more independent items of evidence to identify 18 molecular pathways that were statistically significantly enriched, covering both upstream signaling events and downstream effects. Five molecular pathways significantly enriched for all four different types of addictive drugs were identified as common pathways which may underlie shared rewarding and addictive actions, including two new ones, GnRH signaling pathway and gap junction. We connected the common pathways into a hypothetical common molecular network for addiction. We observed that fast and slow positive feedback loops were interlinked through CAMKII, which may provide clues to explain some of the irreversible features of addiction

KOBAS server: a web-based platform for automated annotation and pathway identification

There is an increasing need to automatically annotate a set of genes or proteins (from genome sequencing, DNA microarray analysis or protein 2D gel experiments) using controlled vocabularies and identify the pathways involved, especially the statistically enriched pathways. We have previously demonstrated the KEGG Orthology (KO) as an effective alternative controlled vocabulary and developed a standalone KO-Based Annotation System (KOBAS). Here we report a KOBAS server with a friendly web-based user interface and enhanced functionalities. The server can support input by nucleotide or amino acid sequences or by sequence identifiers in popular databases and can annotate the input with KO terms and KEGG pathways by BLAST sequence similarity or directly ID mapping to genes with known annotations. The server can then identify both frequent and statistically enriched pathways, offering the choices of four statistical tests and the option of multiple testing correction. The server also has a ‘User Space’ in which frequent users may store and manage their data and results online. We demonstrate the usability of the server by finding statistically enriched pathways in a set of upregulated genes in Alzheimer's Disease (AD) hippocampal cornu ammonis 1 (CA1). KOBAS server can be accessed at

Cyclin-dependent kinase 4 is a novel target in micoRNA-195-mediated cell cycle arrest in bladder cancer cells

AbstractmiRNAs are a class of small-noncoding RNAs capable of negatively regulating gene expression. Here, we found that miR-195 is down-regulated in human bladder cancer tissue versus normal adjacent tissue. To better characterize the role of miR-195 in bladder cancer, we conducted gain of function analysis by transfecting bladder cancer cell line T24 with chemically synthesized miR-195 mimic. We identified CDK4, an early G1 cell cycle regulator, as a novel target of miR-195. Selective over-expression of miR-195 could induce G1-phase arrest in T24 cells, and subsequently inhibit T24 cell growth. These findings indicate that miR-195 could be a potential tumor suppressor in bladder cancer

Preparation of hydrophobic fabrics and effect of fluorine monomers on surface properties

Preparation of hydrophobic cotton fabric based on the self-assembly method was proposed. The cotton fabric was modified with 3-(methacryloyloxy)propyltrimethoxysilane and grafted with trifluoroethyl methacrylate and dodecafluoroheptyl methacrylate through free radical polymerization reaction. The objective of this research work was to investigate the effect of fluorine monomer with different chemical structure deposited on cotton fabric on the hydrophobic property. The chemical structure, surface topography, and surface wettability of the fabrics were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and water contact angle experiments, respectively. The results showed that the as-prepared fabrics exhibited water contact angle of above 140°. It was noticed that the fluorocarbon chain length of a modifier and its chemical structure could strongly affect the hydrophobic property of the modified fabrics, and the increase in fluorine atoms caused an increase in the water contact angle valuesPostprint (published version

Comparative study on body index, nutrient composition, and digestive enzyme activity of Misgurnus anguillicaudatus, Paramisgurnus dabryanus, and Paramisgurnus dabryanus ssp

The current research work was undertaken to compare and analyze the body index, nutrient composition, and digestive enzyme activity of Pond loach (Misgurnus anguillicaudatus), large-scale loach (Paramisgurnus dabryanus), and Taiwan loach (Paramisgurnus dabryanus ssp). Viscerosomatic ratio (VR), condition factor, (CF), W/L and H/L were highest in Taiwan loach (P < 0.05). Muscle protein content was highest, whereas lipid content was lowest in pond loach (P < 0.05). The content of total amino acids (TAA), total essential amino acids (EAA), and delicious amino acids (DAA) in the muscle of pond loach was highest (P < 0.05). The content of polyunsaturated fatty acids (PUFA), monounsaturated fatty acids (MUFA) and linoleic acid was highest in pond loach, Taiwan loach and large-scale loach, respectively (P < 0.05). The trypsin activities and amylase activities of the pond loach were significantly higher than those of the large-scale loach and Taiwan loach in the intestine and liver (P < 0.05). These results indicate that the three kinds of loaches are of high nutritional value and have breeding prospects, among which pond loach has higher nutritional value

In vitro assessment of anti-diabetic potential of 4 kinds of dark tea (Camellia sinensis L.) protein hydrolysates

The contributions of four kinds of dark tea (Camellia sinensis L.) proteins and their hydrolysates to hypoglycemic activity were investigated in vitro. Four kinds of water-extracted dark tea proteins were hydrolyzed with trypsin and Alcalase, respectively. The complete proteins had α-amylase inhibitory activity with half maximal inhibitory concentration (IC50) values ranging from 1.27 to 2.78 mg/mL. Most of the dark tea proteins and hydrolysates significantly inhibited α-glucosidase and dipeptidyl peptidase (DPP-IV), with IC50 values in the range of 0.0103-1.3114 mg/mL and 0.1000-1.3364 mg/mL, respectively. In general, Heimaojian (HMJ) and Qianliang (QL) hydrolysates displayed high α-glucosidase inhibitory activity, while HMJ, Fuzhuan (FZ), and Heizhuan (HZ) hydrolysates exhibited a strong ability to inhibit DPP-IV. This study demonstrates the potential of dark tea proteins and their hydrolysates as a source of functional food and medicine for the control of type 2 diabetes

Long Noncoding RNA-H19 Contributes to Atherosclerosis and Induces Ischemic Stroke via the Upregulation of Acid Phosphatase 5

Objective: Atherosclerosis is closely associated with ischemic stroke, and long noncoding RNA-H19 (lncRNA-H19) might be a potential target for treating atherosclerosis. The present study aimed to investigate the function of lncRNA-H19 in atherosclerosis and to explore a novel therapeutic strategy for ischemic stroke.Methods: Differentially expressed genes (DEGs) in atherosclerosis were screened by searching public database. In combination with the lncRNA-H19-knockout database, potential lncRNA-H19-mediated gene was retrieved and their relationship was identified. In order to assess the detailed regulatory mechanism of lncRNA-H19, we used a lentivirus packaging system to upregulate Acp5 (Acid phosphatase 5) expression in vascular smooth muscle cells (VSMC) and human umbilical vein endothelial cells (HUVECs). The expression of ACP5 was determined by Western Blot, and evaluations of cell proliferation and apoptosis were detected. An ischemic stroke mouse model was established. Atherosclerosis was measured by using plaque area size. The effects H19 on the expression of ACP5 were explored by the overexpression or silence of H19.Results: H19 and ACP5 were associated with Acute Stroke Treatment (TOAST) subtypes of atherosclerotic patients. The target prediction program and dual-luciferase reporter confirmed ACP5 as a direct target of H19. Lentivirus-mediated H19-forced expression upregulated ACP5 protein levels, promoted cell proliferation and suppressed the apoptosis. The plaque area size was larger in ischemic models than controls. The overexpression or silence of H19 increased or reduced the plaque size. The overexpression or silence of H19 resulted in the expression or inhibition of ACP5.Conclusion: IncRNA-H19 promoting ACP5 protein expression contributed to atherosclerosis and increased the risk of ischemic stroke