PathwayBooster: a tool to support the curation of metabolic pathways

Background

Despite several recent advances in the automated generation of draft metabolic reconstructions, the manual curation of these networks to produce high quality genome-scale metabolic models remains a labour-intensive and challenging task.

Results

We present PathwayBooster, an open-source software tool to support the manual comparison and curation of metabolic models. It combines gene annotations from GenBank files and other sources with information retrieved from the metabolic databases BRENDA and KEGG to produce a set of pathway diagrams and reports summarising the evidence for the presence of a reaction in a given organism’s metabolic network. By comparing multiple sources of evidence within a common framework, PathwayBooster assists the curator in the identification of likely false positive (misannotated enzyme) and false negative (pathway hole) reactions. Reaction evidence may be taken from alternative annotations of the same genome and/or a set of closely related organisms.

Conclusions

By integrating and visualising evidence from multiple sources, PathwayBooster reduces the manual effort required in the curation of a metabolic model. The software is available online at http://www.theosysbio.bio.ic.ac.uk/resources/pathwaybooster/.

Electronic supplementary material

The online version of this article (doi:10.1186/s12859-014-0447-2) contains supplementary material, which is available to authorized users.     

A Recurrent Mutation in PARK2 Is Associated with Familial Lung Cancer

PARK2, a gene associated with Parkinson disease, is a tumor suppressor in human malignancies. Here, we show that c.823C>T (p.Arg275Trp), a germline mutation in PARK2, is present in a family with eight cases of lung cancer. The resulting amino acid change, p.Arg275Trp, is located in the highly conserved RING finger 1 domain of PARK2, which encodes an E3 ubiquitin ligase. Upon further analysis, the c.823C>T mutation was detected in three additional families affected by lung cancer. The effect size for PARK2 c.823C>T (odds ratio = 5.24) in white individuals was larger than those reported for variants from lung cancer genome-wide association studies. These data implicate this PARK2 germline mutation as a genetic susceptibility factor for lung cancer. Our results provide a rationale for further investigations of this specific mutation and gene for evaluation of the possibility of developing targeted therapies against lung cancer in individuals with PARK2 variants by compensating for the loss-of-function effect caused by the associated variation.     

Diabetogenic diet-induced insulin resistance associates with lipid droplet proteins and adipose tissue secretome,but not with sexual dimorphic adipose tissue fat accumulation in Wistar rats

The role of sexual dimorphic adipose tissue fat accumulation in the development of insulin resistance is well known. However, whether vitamin A status and/or its metabolic pathway display any sex- or depot (visceral/subcutaneous)-specific pattern and have a role in sexual dimorphic adipose tissue development and insulin resistance are not completely understood. Therefore, to assess this, 5 weeks old Wistar male and female rats of eight from each sex were provided either control or diabetogenic (high fat, high sucrose) diet for 26 weeks. At the end, consumption of diabetogenic diet increased the visceral fat depots (p < 0.001) in the males and subcutaneous depot (p < 0.05) in the female rats, compared to their sex-matched controls. On the other hand, it caused adipocyte hypertrophy (p < 0.05) of visceral depot (retroperitoneal) in the females and subcutaneous depot of the male rats. Although vitamin A levels displayed sex- and depot-specific increase due to the consumption of diabetogenic diet, the expression of most of its metabolic pathway genes in adipose depots remained unaltered. However, the mRNA levels of some of lipid droplet proteins (perilipins) and adipose tissue secretory proteins (interleukins, lipocalin-2) did display sexual dimorphism. Nonetheless, the long-term feeding of diabetogenic diet impaired the insulin sensitivity, thus affected glucose clearance rate and muscle glucose-uptake in both the sexes of rats. In conclusion, the chronic consumption of diabetogenic diet caused insulin resistance in the male and female rats, but did not corroborate with sexual dimorphic adipose tissue fat accumulation or its vitamin A status.     

Glucose lowering effect of transgenic human insulin-like growth factor-I from rice: <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis>studies

Background  

Human insulin-like growth factor-I (hIGF-I) is a growth factor which is highly resemble to insulin. It is essential for cell proliferation and has been proposed for treatment of various endocrine-associated diseases including growth hormone insensitivity syndrome and diabetes mellitus. In the present study, an efficient plant expression system was developed to produce biologically active recombinant hIGF-I (rhIGF-I) in transgenic rice grains.     

A comparative genomics study of genetic products potentially encoding ladderane lipid biosynthesis

Background  

The fatty acids of anaerobic ammonium oxidizing (anammox) bacteria contain linearly concatenated cyclobutane moieties, so far unique to biology. These moieties are under high ring strain and are synthesised by a presently unknown biosynthetic pathway.     

JNets: Exploring networks by integrating annotation

Background  

A common method for presenting and studying biological interaction networks is visualization. Software tools can enhance our ability to explore network visualizations and improve our understanding of biological systems, particularly when these tools offer analysis capabilities. However, most published network visualizations are static representations that do not support user interaction.