CytoSVM: an advanced server for identification of cytokine-receptor interactions

The interactions between cytokines and their complementary receptors are the gateways to properly understand a large variety of cytokine-specific cellular activities such as immunological responses and cell differentiation. To discover novel cytokine-receptor interactions, an advanced support vector machines (SVMs) model, CytoSVM, was constructed in this study. This model was iteratively trained using 449 mammal (except rat) cytokine-receptor interactions and about 1 million virtually generated positive and negative vectors in an enriched way. Final independent evaluation by rat's data received sensitivity of 97.4%, specificity of 99.2% and the Matthews correlation coefficient (MCC) of 0.89. This performance is better than normal SVM-based models. Upon this well-optimized model, a web-based server was created to accept primary protein sequence and present its probabilities to interact with one or several cytokines. Moreover, this model was applied to identify putative cytokine-receptor pairs in the whole genomes of human and mouse. Excluding currently known cytokine-receptor interactions, total 1609 novel cytokine-receptor pairs were discovered from human genome with probability ∼80% after further transmembrane analysis. These cover 220 novel receptors (excluding their isoforms) for 126 human cytokines. The screening results have been deposited in a database. Both the server and the database can be freely accessed at http://bioinf.xmu.edu.cn/software/cytosvm/cytosvm.php

GEPS: the Gene Expression Pattern Scanner

Gene Expression Pattern Scanner (GEPS) is a web-based server to provide interactive pattern analysis of user-submitted microarray data for facilitating their further interpretation. Putative gene expression patterns such as correlated expression, similar expression and specific expression are determined globally and systematically using geometric comparison and correlation analysis methods. These patterns can be visualized via linear plot with quantitative measures. User-defined threshold value is allowed to customize the format of the pattern search results. For better understanding of gene expression, patterns derived from 329 205 non-redundant gene expression records from the GNF SymAltas and the Gene Expression Omnibus are also provided. These profiles cover 24 277 human genes in 79 tissues, 32 905 mouse genes in 61 tissues and 4201 rat genes in 44 tissues. GEPS is available at

The Genomes of Oryza sativa: A History of Duplications

We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000–40,000. Only 2%–3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)