Identifying significant associations of orthologous simple sequence repeats with gene ontologies.

Simple Sequence Repeats (SSRs), also known as microsatellites, regulate gene functions. SSR mutations in a disease gene may cause various genetic disorders. To identify putative functional SSRs, a web-based system, Gene Ontology SSR Hierarchy (GOSH), was developed to facilitate discovery of significant associations between SSRs and Gene Ontology (GO) terms. Using the GO hierarchy term structure, GOSH assists users with selecting functional or biological gene subsets. Significant SSR patterns are retrieved and identified via comprehensive overrepresentation analysis within a target gene subset and by comparing results with orthologous genes. Pattern relationships between different biological subsets or supersets can be observed by using the GO hierarchy structure directly. GOSH also supports GO searching through identified significant SSR patterns and all GO terms possessing such patterns are listed for consultation. GOSH is the first comprehensive and efficient online mining tool for discovering significant orthologous SSR patterns in GO terms and is available at http://gosh.cs.ntou.edu.tw/.

Serum HCV RNA level is not associated with insulin resistance and metabolic syndrome in chronic hepatitis C patients with genotype 1 or 2 infection.

BACKGROUND: Previous reports have indicated that insulin resistance (IR) is associated with chronic hepatits C virus (HCV) infection. However, the correlations between IR, metabolic syndrome (MS), and serum HCV RNA levels are still controversial. The aim of this study was to determine the relationships between IR, MS, and HCV RNA in patients with chronic genotype 1 or 2 HCV infection. METHODS: One hundred and twenty subjects with chronic genotype 1 or 2 HCV infection with complete clinical data were prospectively enrolled. Baseline and laboratory data were collected and analyzed. IR was defined as a homeostatic model assessment- IR (HOMA-IR) score > 2.5. RESULTS: Of the 120 patients, 47 (39.2%) had a HOMA-IR > 2.5, and 42 (35%) met the criteria for MS. IR was significantly associated with a high body mass index (p < 0.0001), high waist circumference (p < 0.0001) and high triglyceride level (p = 0.025). IR was an independent predictor of MS. However, in multivariate linear regression analysis, the serum HCV RNA level was not significantly different in chronic hepatitis C patients with or without IR (p = 0.761), and with or without MS (p = 0.292). CONCLUSIONS: IR and MS are not uncommon in patients with chronic hepatitis C. The serum HCV RNA level is not associated with the presence of IR or MS in chronic hepatitis C patients with genotype 1 or 2 infection. The impact of hepatitis C virus on IR is not dose responsive.

Functional pathway mapping analysis for hypoxia-inducible factors.

BACKGROUND: Hypoxia-inducible factors (HIFs) are transcription factors that play a crucial role in response to hypoxic stress in living organisms. The HIF pathway is activated by changes in cellular oxygen levels and has significant impacts on the regulation of gene expression patterns in cancer cells. Identifying functional conservation across species and discovering conserved regulatory motifs can facilitate the selection of reference species for empirical tests. This paper describes a cross-species functional pathway mapping strategy based on evidence of homologous relationships that employs matrix-based searching techniques for identifying transcription factor-binding sites on all retrieved HIF target genes. RESULTS: HIF-related orthologous and paralogous genes were mapped onto the conserved pathways to indicate functional conservation across species. Quantitatively measured HIF pathways are depicted in order to illustrate the extent of functional conservation. The results show that in spite of the evolutionary process of speciation, distantly related species may exhibit functional conservation owing to conservative pathways. The novel terms OrthRate and ParaRate are proposed to quantitatively indicate the flexibility of a homologous pathway and reveal the alternative regulation of functional genes. CONCLUSION: The developed functional pathway mapping strategy provides a bioinformatics approach for constructing biological pathways by highlighting the homologous relationships between various model species. The mapped HIF pathways were quantitatively illustrated and evaluated by statistically analyzing their conserved transcription factor-binding elements. KEYWORDS: hypoxia-inducible factor (HIF), hypoxia-response element (HRE), transcription factor (TF), transcription factor binding site (TFBS), KEGG (Kyoto Encyclopedia of Genes and Genomes), cross-species comparison, orthology, paralogy, functional pathway.

FibroQ: an easy and useful noninvasive test for predicting liver fibrosis in patients with chronic viral hepatitis.

BACKGROUND: Liver biopsy-the gold standard in assessing liver histology-is recommended before all antiviral treatment. However, this procedure may cause complications, is costly, and is limited by sampling errors. Hence, noninvasive tests have been proposed to assess the severity of hepatic fibrosis. We propose a novel noninvasive index for predicting liver fibrosis, named fibro-quotient (FibroQ), and compared the diagnostic accuracies of FibroQ, aspartate aminotransferase (AST)-to-platelet ratio index (APRI), and AST/alanine aminotransferase (ALT) ratio (AAR). METHODS: This retrospective cohort study included 140 consecutive patients with chronic viral hepatitis who had undergone percutaneous liver biopsy before treatment at the Chang Gung Memorial Hospital, Chiayi from May 2005 through December 2007. The clinical data including sex, age, AST, ALT, platelet count, prothrombin time (PT) international normalized ratio (INR), and the Metavir fibrosis score (F0 to F4) of liver histology were recorded. APRI, AAR, and FibroQ were calculated. Receiver operating characteristic (ROC) curves were constructed to compare the accuracies of these three noninvasive tests in predicting significant fibrosis in patients with chronic viral hepatitis. RESULTS: FibroQ performed better than APRI, but was equal to AAR, in the prediction of significant fibrosis [area under the receiver operating characteristic curve (AUC): 0.783 vs 0.631 (p = 0.02) and 0.783 vs 0.733 (p = 0.26), respectively] and cirrhosis (AUC: 0.791 vs 0.634 (p = 0.03), and 0.791 vs 0.782 (p= 0.47), respectively). Using FibroQ below the lower cutoff value (0.6) and above the higher cutoff value (1.6), 108 of 140 (77.1%) patients could be identified correctly to have or not have significant fibrosis. CONCLUSION: FibroQ, a novel noninvasive test, is an useful and easy tool to evaluate liver fibrosis in patients with chronic viral hepatitis and has better accuracy than APRI and is equal to AAR. Further prospective studies are warranted to validate its efficacy.

Clinical features and outcome of chronic viral hepatitis with acute exacerbation in patients with concurrent infections of hepatitis B and C virus.

BACKGROUND/AIMS: Studies have shown that concurrent infection of hepatitis B virus and hepatitis C virus may be associated with severe forms of chronic liver disease or with rapid progression. However, very little is known about the role and course of concurrent HBV and HCV infection in patients with acute viral hepatitis. METHODS: This study retrospectively compared the clinical features of 83 patients diagnosed with HBV- or HCV-related chronic hepatitis with acute exacerbation (12 with concurrent HBV and HCV infection, 46 with HBV infection alone, and 25 with HCV infection alone) encountered at Chia-Yi Chang Gung Memorial Hospital, Taiwan, between January 2003 and December 2005. RESULTS: The clinical course of chronic hepatitis with acute exacerbation in patients with concurrent HBV and HCV infection is similar to patients with single HBV infection, and more severe than patients with single HCV infection, evidenced by increased hepatic decompensation (P = 0.05), failure (P = 0.036), and mortality (P = 0.036). Elevated serum HCVRNA-negative percentage in HBVDNA-positive patients and low serum HBVDNA concentrations in HCVRNA-positive patients imply reciprocal interference of HBV and HCV in patients with concurrent HBV and HCV infections during acute-phase hepatitis. In patients with concurrent HBV and HCV infection, the mortality rate for detectable HBVDNA patients seemed higher than that for undetectable HBVDNA patients, although it did not reach statistical significance (P = 0.066). CONCLUSIONS: Virus interference existed in chronic hepatitis with acute exacerbation patients with concurrent HBV and HCV infections. Clinical outcome for patients positive for serum HBVDNA was much worse than those negative for serum HBVDNA. When chronic hepatitis with acute exacerbation occurs in patients with concurrent HBV and HCV infection, aggressive management should be investigated and antiviral therapy targeting of HBV infection should be administered early.