Biological networks and epistasis in genome-wide association studies

Over the last few years, technological improvements have made possible the genotyping of hundreds of thousands of SNPs, enabling whole-genome association studies. The first genome-wide association studies have recently been completed to detect causal variant for complex traits. Although increasing evidence suggests that interaction between loci, such as epistasis between two loci, should be considered, most of these studies proceed by considering each SNP independently. One reason for this choice is that looking at all pairs of SNPs increases dramatically the number of tests (approximatively 50 billions of tests for a 300,000 SNPs data set) that faces with computational limitation and strong multiple testing correction.
We proposed to reduce the number of tests by focusing on pairs of SNPs that belong to genes known to interact in some metabolic network. Although some interactions might be missed, these pairs of genes are good candidates for epistasis. Furthermore the use of protein interaction databases (such as the STRING database) may reduce the number of tests by a factor of 5,000.
Results using this approach will be presented on simulated data sets and on public data sets.
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Spectral characterisation of red pigment in Italian-type dry-cured ham. Increasing lipophilicity druing processing and maturation

Spectroscopic studies of Parma ham during processing revealed a gradual transformation of muscle myoglobin, initiated by salting and continuing during ageing. Electron spin resonance spectra did, however, conclusively show that the pigment in dry-cured Parma ham at no stage is a nitrosyl complex of ferrous myoglobin as found in brine-cured ham and Spanish Serrano hams. Both near-infra red reflectance spectra of sliced ham and UV/visible absorption spectra of extract of hams, obtained with aqueous buffer or acetone, showed the presence of different red pigments at varying processing stages for both solvents. Especially, the pigment extracted with aqueous buffer exhibited unique spectral features different from those of well-known myoglobin derivatives. At the end of processing, the pigment(s) becomes less water extractable, while the fraction of red pigment(s) extractable with acetone/water (75%/25%) increases throughout the processing time up to full maturation at 18 months. The chemical identity of the 6th ligand of myoglobin could not be conclusively established, but possible candidates are discussed. The partition of the pigment(s) between pentane and acetone/water showed a strong preference for pentane, suggesting that only the heme moiety is present in the acetone/water extract, and that Parma ham pigment is gradually transformed from a myoglobin derivative into a non-protein heme complex, which was found to be thermally stable in acetone/water solutio

Thermal and photochemical degradation of myoglobin pigments in relation to colour stability of sliced dry-cured Parma ham and sliced dry-cured ham produced with nitrite salt

Lipophilic and hydrophilic extracts of the red pigments from Parma ham and nitrosylated pigment of dry-cured ham produced with nitrite salt were prepared with acetone/water (75/25 v/v %) solution and aqueous phosphate buffer, respectively. The spectral characteristics differed for both the lipophilic and the hydrophilic Parma ham pigment compared with the dry-cured ham produced with nitrite salt. The red lipophilic pigment(s) extractable from Parma ham was(were) found to be very stable towards thermal degradation in acetone/water (75/25 v/v %) solution for temperatures up to 70 °C in contrast to the lipophilic pigment(s) extractable from dry-cured ham produced with nitrite salt, which was(were) found to have an energy of activation of 99 kJ/mol for thermal degradation. In contrast, quantum yields for photodegradation of the lipophilic ham pigments exposed to 366 nm (420 nm) monochromatic light were larger for Parma ham than for nitrite-cured ham [1.6×10–5 (6.9×10–6) versus 1.6×10–6 (2×10–6) mol einstein–1] as determined for acetone/water (75/25 v/v %) solution. In agreement with these findings for the extracted lipophilic pigments, sliced Parma ham showed better colour stability than sliced dry-cured ham produced with nitrite salt, when stored in the dark at low oxygen concentration, in contrast to a faster initial discolouration for Parma ham when exposed to light, as shown for chilled storage for 35 days under retail conditions for the two products each packed at two oxygen levels (0.4 and 21%)

Studies on the antioxidative activity of red pigments in Italian-type dry-cured ham

Aqueous phosphate buffer extracts and acetone/water extracts of pigments from Parma ham were assessed as antioxidants by (1) electron spin resonance spectroscopy using a spin probing technique to evaluate their efficiencies as scavengers of free radicals, and (2) by electrochemical measurement of oxygen depletion rate in an aqueous methyl linoleate emulsion to evaluate their efficiencies as chain-breaking antioxidant, and using both methods, compared with the effect of apomyoglobin and nitrosylmyoglobin. Aqueous phosphate extracts and acetone/water extracts of Parma ham pigment both scavenged a semi-stable nitroxide radical (Fremy's salt), and both extracts reduced the rate of oxygen consumption for lipid peroxidation (initiated by metmyoglobin) very efficiently. For apomyoglobin no antioxidative capacity was observed, and the heme moiety of the pigment(s) of Parma ham were concluded to have antioxidative properties. The more lipophilic pigment, as extracted by acetone/water, had the most significant effect, and its ability to inhibit lipid oxidation was further tested in a model food system based on cooked pork. The lipid oxidation was increasingly inhibited by increasing additions from 0.12 ppm to 0.24 ppm Parma ham pigment, and the pigment protected a-tocopherol against degradation in a concentration dependent manner

Cyclostationary shot noise in mesoscopic measurements

We discuss theoretically a setup where a time-dependent current consisting of a DC bias and two sinusoidal harmonics is driven through a sample. If the sample exhibits current-dependent shot noise, the down-converted noise power spectrum varies depending on the local-oscillator phase of the mixer. The theory of this phase-dependent noise is applied to discuss the measurement of the radio-frequency single-electron transistor. We also show that this effect can be used to measure the shot noise accurately even in nonlinear high-impedance samples.Comment: 3 pages, 2 figure

Hyperspectral Image Processing Using Locally Linear Embedding

We describe a method of processing hyperspectral images of natural scenes that uses a combination of k-means clustering and locally linear embedding (LLE). The primary goal is to assist anomaly detection by preserving spectral uniqueness among the pixels. In order to reduce redundancy among the pixels, adjacent pixels which are spectrally similar are grouped using the k-means clustering algorithm. Representative pixels from each cluster are chosen and passed to the LLE algorithm, where the high dimensional spectral vectors are encoded by a low dimensional mapping. Finally, monochromatic and tri-chromatic images are constructed from the k-means cluster assignments and LLE vector mappings. The method generates images where differences in the original spectra are reflected in differences in the output vector assignments. An additional benefit of mapping to a lower dimensional space is reduced data size. When spectral irregularities are added to a patch of the hyperspectral images, again the method successfully generated color assignments that detected the changes in the spectra