Discovering the hidden sub-network component in a ranked list of genes or proteins derived from genomic experiments

Genomic experiments (e.g. differential gene expression, single-nucleotide polymorphism association) typically produce ranked list of genes. We present a simple but powerful approach which uses protein–protein interaction data to detect sub-networks within such ranked lists of genes or proteins. We performed an exhaustive study of network parameters that allowed us concluding that the average number of components and the average number of nodes per component are the parameters that best discriminate between real and random networks. A novel aspect that increases the efficiency of this strategy in finding sub-networks is that, in addition to direct connections, also connections mediated by intermediate nodes are considered to build up the sub-networks. The possibility of using of such intermediate nodes makes this approach more robust to noise. It also overcomes some limitations intrinsic to experimental designs based on differential expression, in which some nodes are invariant across conditions. The proposed approach can also be used for candidate disease-gene prioritization. Here, we demonstrate the usefulness of the approach by means of several case examples that include a differential expression analysis in Fanconi Anemia, a genome-wide association study of bipolar disorder and a genome-scale study of essentiality in cancer genes. An efficient and easy-to-use web interface (available at http://www.babelomics.org) based on HTML5 technologies is also provided to run the algorithm and represent the network.     

Environmental factors affecting the densities of owls in Polish farmland during 1980–2005

During the last decades, farmland habitats in central European countries have changed significantly, seriously affecting populations of many farmland bird species. We compiled available published data on densities of three owl species, Athene noctua, Asio otus and Strix aluco collected in the Polish farmland. All results of censuses based on the playback method conducted between 1980–2005 were included in the analysis. The proportions of grassland, fields, built-up land and forest at each studied plot were estimated and used as predictors in additive models. Proportions of main land use types, extracted with the principal component analysis, explained much of the variation found in owl densities, although some of the relationships were nonlinear. In general, owl densities were found to be affected positively by a high percentage of grasslands and built-up land, and negatively by the amount of fields and forests. Little owl densities showed a significant negative trend over the study period. It seems that high prey availability is an important factor accounting for the positive relationship between grassland proportion and owl density. The significant decrease in grassland areas and increase in forest coverage that were recently recorded in Poland may thus negatively affect populations of the three owl species studied here.     

Monensin A acid complexes as a model of electrogenic transport of sodium cation

New Monensin A acid complexes with water molecule, sodium chloride and sodium perchlorate were obtained and studied by X-ray and (1)H, (13)C NMR and FT-IR methods as well as ab initio calculations. The crystal structure of the complexes indicates the complexation of the water molecule and Na(+) cation in the pseudo-cycle conformation of the Monensin acid molecule stabilised by intramolecular hydrogen bonds. Important for stabilisation of this structure is also the intermolecular hydrogen bonds with water molecule or the coordination bonds with Na(+) cation. It is demonstrated that the counterions forming intermolecular hydrogen bonds with OH groups influence the strength of the intramolecular hydrogen bonds, but they have no influence on the formation of pseudo-cyclic structure. Spectroscopic studies of the complexes in dichloromethane solution have shown that the pseudo-cyclic structure of the compounds is conserved. As follows from the ab initio calculations, the interactions between the Na(+) cation and the electronegative oxygen atoms of Monensin acid totally change the molecular electrostatic potential around the supramolecular Monensin acid-Na(+) cationic complex relative to that of the neutral Monensin acid molecule.     

Effect of age and sex on digestive tract morphometry of guinea fowl (Numida meleagris L.)

As guinea fowl age, their body weights and length of the esophagus and crop increased significantly, and relative length (cm x 100 g b.w(-1)) of the small intestine, caeca and total intestine decreased significantly (P < or = 0.05) in males and females. In addition, 52-week-old males had a significantly higher percentage length of rectum and heart weight, and females a significantly higher gizzard weight compared to 13-week-old birds. Compared to females, adult males differed significantly (P < or = 0.05) in the length of caeca and also in the proportion of the gizzard, proventriculus, heart and liver in total weight.     

Contribution of STAT4 gene single-nucleotide polymorphism to systemic lupus erythematosus in the Polish population

The STAT4 has been found to be a susceptible gene in the development of systemic lupus erythematosus (SLE) in various populations. There are evident population differences in the context of clinical manifestations of SLE, therefore we investigated the prevalence of the STAT4 G > C (rs7582694) polymorphism in patients with SLE (n = 253) and controls (n = 521) in a sample of the Polish population. We found that patients with the STAT4 C/G and CC genotypes exhibited a 1.583-fold increased risk of SLE incidence (95 % CI = 1.168-2.145, p = 0.003), with OR for the C/C versus C/G and G/G genotypes was 1.967 (95 % CI = 1.152-3.358, p = 0.0119). The OR for the STAT4 C allele frequency showed a 1.539-fold increased risk of SLE (95 % CI = 1.209-1.959, p = 0.0004). We also observed an increased frequency of STAT4 C/C and C/G genotypes in SLE patients with renal symptoms OR = 2.259 (1.365-3.738, p = 0.0014), (p (corr) = 0.0238) and in SLE patients with neurologic manifestations OR = 2.867 (1.467-5.604, p = 0.0016), (p (corr) = 0.0272). Moreover, we found a contribution of STAT4 C/C and C/G genotypes to the presence of the anti-snRNP Ab OR = 3.237 (1.667-6.288, p = 0.0003), (p (corr) = 0.0051) and the presence of the anti-Scl-70 Ab OR = 2.665 (1.380-5.147, p = 0.0028), (p (corr) = 0.0476). Our studies confirmed an association of the STAT4 C (rs7582694) variant with the development of SLE and occurrence of some clinical manifestations of the disease.     

Genetic polymorphism of the iron-regulatory protein-1 and -2 genes in age-related macular degeneration

Iron can be involved in the pathogenesis of AMD through the oxidative stress because it may catalyze the Haber–Weiss and Fenton reactions converting hydrogen peroxide to free radicals, which can induce cellular damage. We hypothesized that genetic polymorphism in genes related to iron metabolism may predispose individuals to the development of AMD and therefore we checked for an association between the g.32373708 G>A polymorphism (rs867469) of the IRP1 gene and the g.49520870 G>A (rs17483548) polymorphism of the IRP2 gene and AMD risk as well as the modulation of this association by some environmental and life-style factors. Genotypes were determined in DNA from blood of 269 AMD patients and 116 controls by the allele-specific oligonucleotide-restriction fragment length polymorphism and the polymerase chain reaction-restriction fragment length polymorphism. An association between AMD, dry and wet forms of AMD and the G/G genotype of the g.32373708 G>A-IRP1 polymorphism was found (OR 3.40, 4.15, and 2.75). On the other hand, the G/A genotype reduced the risk of AMD as well as its dry or wet form (OR 0.23, 0.21, 0.26). Moreover, the G allele of the g.49520870 G>A-IRP2 polymorphism increased the risk of the dry form of the disease (OR 1.51) and the A/A genotype and the A allele decreased such risk (OR 0.43 and 0.66). Our data suggest that the g.32373708 G>A-IRP1 and g.49520870 G>A-IRP2 polymorphisms may be associated with increased risk for AMD.     

Influence of Incubation Conditions on Hydrolysis Efficiency and Iodine Enrichment in Baker’s Yeast

The influence of incubation conditions, enzyme type, hydrolysis time, and potassium iodide concentration on hydrolysis and iodine enrichment were studied in supernatant and pellets of Saccharomyces cervisiae hydrolysates. The type of enzyme used and incubation time significantly influence hydrolysis efficiency and protein concentration in supernatant and pellet. The highest protein hydrolysis efficiency was obtained by 24-h incubation with papain. Significantly lower values were observed for pepsin and autolysis. The potassium iodide concentration influences the iodine content of supernatant and pellet, but not hydrolysis. Iodide enrichment of supernatant and pellet depends on the concentration of iodide using during incubation. High concentration of iodide and long incubation times were the conditions for optimal iodide enrichment and high-protein hydrolysates. The optimal hydrolysis efficiency and iodine enrichment were obtained during 24-h incubation with papain in a 4.5-mM potassium iodide medium. The efficiency reached 98.22% with iodine concentrations of 2,664.91 and 9,200.67 μg/g iodine in pellet and supernatant, respectively.