Normalization of Illumina Infinium whole-genome SNP data improves copy number estimates and allelic intensity ratios

Background  

Illumina Infinium whole genome genotyping (WGG) arrays are increasingly being applied in cancer genomics to study gene copy number alterations and allele-specific aberrations such as loss-of-heterozygosity (LOH). Methods developed for normalization of WGG arrays have mostly focused on diploid, normal samples. However, for cancer samples genomic aberrations may confound normalization and data interpretation. Therefore, we examined the effects of the conventionally used normalization method for Illumina Infinium arrays when applied to cancer samples.     

The role of weakly polar and H-bonding interactions in the stabilization of the conformers of FGG, WGG, and YGG: an aqueous phase computational study

The energetics of intramolecular interactions on the conformational potential energy surface of the terminally protected N-Ac-Phe-Gly-Gly-NHMe (FGG), N-Ac-Trp-Gly-Gly-NHMe (WGG), and N-Ac-Tyr-Gly-Gly-NHMe (YGG) tripeptides was investigated. To identify the representative conformations, simulated annealing molecular dynamics (MD) and density functional theory (DFT) methods were used. The interaction energies were calculated at the BHandHLYP/aug-cc-pVTZ level of theory. In the global minima, 10%, 31%, and 10% of the stabilization energy come from weakly polar interactions, respectively, in FGG, WGG, and YGG. In the prominent cases 46%, 62%, and 46% of the stabilization energy is from the weakly polar interactions, respectively, in FGG, WGG, and YGG. On average, weakly polar interactions account for 15%, 34%, and 9% of the stabilization energies of the FGG, WGG, and YGG conformers, respectively. Thus, weakly polar interactions can make an important energetic contribution to protein structure and function. (c) 2008 Wiley Periodicals, Inc. Biopolymers 89: 1002-1011, 2008.This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com.     

Site-specific endonuclease BstM6I from Bacillus stearothermophilus M6]

A site-specific endonuclease activity was found in extract of Bacillus stearothermophilus M6 isolated from molasses. The functionally pure enzyme designated as BstM6I was obtained by consecutive chromatographies on blue sepharose, hydroxyapatite, and heparin-sepharose. The endonuclease recognizes the nucleotide sequence CC decreases WGG in double-stranded DNA and cleaves it as indicated by the arrow to give one-nucleotide 5'-protruding ends. Consequently, the site-specific endonuclease BstM6I is an isoshizomer of BstNI.     

Whole-genome genotyping with the single-base extension assay

We describe an efficient, accurate and robust whole-genome genotyping (WGG) assay based on a two-color, single-base extension (SBE), single-nucleotide polymorphism (SNP)-scoring step. We report genotyping results for biallelic International HapMap quality control (QC) SNPs using a single probe per locus. We show scalability, throughput and accuracy of the system by resequencing homozygous loci from our 100k Human-1 Genotyping BeadChip.     

Optical Absorption of Thin Film Solar Cells with Hybrid Arranged Bottom Grating

Crystalline silicon thin film solar cells with hybrid arranged bottom grating are proposed. Optical absorption efficiency and photocurrent density are calculated to get optimized bottom grating parameters. Compared with mono arranged Ag grating or Al-doped zinc-oxide grating, hybrid arranged bottom grating could couple more near-infrared region lights into the active absorber layer. Optical absorption enhancement profiles are plotted for monolayer grating solar cells with four different bottom grating arrangements, which agree with dispersion characteristics well. The absorption enhancement profiles illustrate the mechanism of the more coupling of near-infrared lights. Electrical modeling is considered in the end and it is found that hybrid arranged bottom grating’s thin film solar cell outperforms the thin film solar cells with mono arranged bottom gratings evidently.     

Excitation and Optimization Modeling of Surface Plasmon Polaritons in a Concentric Circular Metallic Grating Film

Interaction behavior between surface plasmon polaritons (SPPs) and Hankel-distributed diffracted waves (DWs) on a silver concentric circular grating film is studied using a rigorous coupled-wave technique for circular structure. It is shown that the numerical technique reveals the excitation characteristics of SPPs in the circular metal grating as well as provides an accurate calculation of SPP intensities for further optimization designs. Results show that the SPPs can be excited by various DWs through the control of wavelength and angle of the incident light. The most efficient excitation of SPPs from this circular metal grating structure can be obtained from the +1^st-order DW under a normal incidence with wavelength close to the grating period, and the optimal thickness and duty cycle of the grating are found to be 370 and 0.5 nm, respectively. It is shown that the optimized intensity of SPPs excited from circular metal grating can be higher than that from strip metal grating by over one order of magnitude.     

Plasmonic Band Gap: Role of the Slit Width in 1D Metallic Grating on Higher Refractive Index Substrate

This paper reports the excitation of surface plasmon polaritons (SPPs) and associated plasmonic band gap (PBG) while using TM plane wave interacting with 1D metallic grating on higher refractive index GaP substrate. A simple method is introduced to estimate the PBG which is crucial for many plasmonic devices. The PBG is estimated by measuring the transmission spectra obtained through the plasmonic grating structures when slit width is varied while periodicity and the thickness of the gold (Au) film remained fixed. The PBG is observed for the grating devices whose slit width is less than one third of the periodicity which is caused by the presence of a higher plasmonic mode. The PBG is absent for the grating device whose slit width is slightly less than half and greater than one third of the periodicity. Such grating devices support only a fundamental plasmonic mode because the profile/shape of the slit in the grating device is more like a sinusoidal nature. Furthermore, such grating offers intermediate scattering to the incident light and the SPP as well which in turn couple more incident energy to the SPPs. Far-field modelling results also support the results obtained through experiment.

     

Synchronous Tuning of Twined Resonance Modes with Controllable Spectral Separation in Plasmonic Gratings

We investigated angle-resolved tuning performance of the double resonance modes of waveguide metallic grating structures, where the incident angle was changed in the plane formed by the extending direction of the grating lines and the wave vector with the grating plane tilted with respect to the vertical axis. Double resonance modes were observed due to tilting of the grating, which were tuned simultaneously to the blue with increasing the angle of incidence. The spectral separation between the resonance modes can be adjusted simply by changing the tilting angle of the grating. Such a double resonance device is important for exploring multichannel optical filters, optical switching device, or sensors.     

Characterization of Grating Coupled Surface Plasmon Polaritons Using Diffracted Rays Transmittance

A method to sense the excitation of surface plasmon polariton (SPP) on metallic grating device using the transmitted signal will be presented. The grating transmittance signal will be fully characterized varying the light incident angle and azimuthal grating orientation by means of the SPP vector model and rigorous coupled-wave analysis simulation. Simulation results will be compared with experimental measurements obtained with a 635 nm wavelength laser in the transverse magnetic polarization mode. The laser will light grating devices in contact with either air or water through a customized microfluidic chamber. A characterization of the diffracted rays will show the relationship between the grating coupling configuration and the Kretschmann one. In fact, the diffracted ray affected by SPP resonance is transmitted with an output angle which is the same incident angle that should be used to excite SPP in Kretschmann configuration. Lastly, the grating parameters (amplitude and metal thickness) impact on transmittance signal will be analyzed with respect to the order zero reflectance signal.     

Directional performances with moving plaids: component-related and plaid-related processing modes coexist.

A moving grating oriented +/- 45 degrees to the vertical can be perceived at choice as drifting along a left-right or up-down directional axis. When the drifting stimulus is presented alone, direction discrimination thresholds are independent of the specified response-axis. However, they strongly depend on it when the moving stimulus is superimposed on a vertical or horizontal stationary grating. Facilitation is always obtained when the drift direction of the intersections of the two gratings ('blobs') is collinear with the response-axis (i.e. when the orientations of the stationary grating and of the response-axis coincide), while inhibition is observed in the 'noncollinear' cases (i.e. when the orientations of the stationary grating and of the response-axis are orthogonal). These results are generalized in a series of reaction time (RT) experiments where the stimulus configuration described above was set at suprathreshold contrasts and where the orientation/direction of the drifting grating was variable. RT increased when the angle between the response-axis and the direction of the drifting grating increased (uncertainty effect), whether the test stimulus was presented alone, or superimposed on the stationary grating. The uncertainty effect was, however, significantly decreased under 'collinearity' conditions. The attenuation of the uncertainty effect was proportional with the velocity of the blobs and about equal in amount to the RT decrease obtained through the manipulation of the velocity of the drifting grating when presented alone (velocity effect). This observation strongly suggests that both component- and blob/plaid-related information contribute to the directional perception of a compound stimulus and that they sum algebraically.     

High-Performance Tunable Plasmonic Absorber Based on the Metal-Insulator-Metal Grating Nanostructure

Plasmonics - A new high-performance plasmonic absorber based on the metal-insulator-metal grating nanostructure is proposed and numerically studied. The effect of geometric parameters of grating...     

Assessment of spatial acuity at the fingertip with grating (JVP) domes: validity for use in an elderly population

JVP domes are of a set of small grating surfaces recently introduced for cutaneous spatial resolution measurement. The gratings are placed on the skin and subjects are required to identify the orientation of grooves and bars. The finest grating whose orientations are discriminated reliably (75% correct) provides an estimate of the spatial resolution limit in the tested area. In the present study, we sought to determine the capacity of elderly subjects to resolve such grating stimuli in order to obtain normative data for this population. Thirty-two elderly individuals in good health (range: 60-88 years) were assessed for their ability to perceive grating orientation at the tip of the dominant index finger. Testing proceeded from the widest grating dome (3 mm) to the next (e.g., 2 mm), until the performance level dropped below 75% correct discrimination. The grating orientation task proved to be very difficult for most subjects and only a minority (14/32) was able to provide reliable reports of grating orientation even with presentation of the widest dome available (3 mm). Accordingly, individual grating resolution thresholds were often considerably higher (>2.5 mm, n = 26) than values previously reported in young adults for the fingertip region (approximately 1 mm). These results suggest that the current set of grating domes may not be adequate for spatial acuity measurement at the fingertip of older adults. New larger grating dimensions should be added to the set presently available to improve their sensitivity for an older population.     

Monomeric restriction endonuclease BcnI in the apo form and in an asymmetric complex with target DNA

Restriction endonuclease BcnI cleaves duplex DNA containing the sequence CC/SGG (S stands for C or G, / designates a cleavage position) to generate staggered products with single nucleotide 5'-overhangs. Here, we show that BcnI functions as a monomer that interacts with its target DNA in 1:1 molar ratio and report crystal structures of BcnI in the absence and in the presence of DNA. In the complex with DNA, BcnI makes specific contacts with all five bases of the target sequence and not just with a half-site, as the protomer of a typical dimeric restriction endonuclease. Our data are inconsistent with BcnI dimerization and suggest that the enzyme introduces double-strand breaks by sequentially nicking individual DNA strands, although this remains to be confirmed by kinetic experiments. BcnI is remotely similar to the DNA repair protein MutH and shares approximately 20% sequence identity with the restriction endonuclease MvaI, which is specific for the related sequence CC/WGG (W stands for A or T). As expected, BcnI is structurally similar to MvaI and recognizes conserved bases in the target sequence similarly but not identically. BcnI has a unique machinery for the recognition of the central base-pair.     

Assessment of spatial acuity at the fingertip with grating (JVP) domes: validity for use in an elderly population

JVP domes are of a set of small grating surfaces recently introduced for cutaneous spatial resolution measurement. The gratings are placed on the skin and subjects are required to identify the orientation of grooves and bars. The finest grating whose orientations are discriminated reliably (75% correct) provides an estimate of the spatial resolution limit in the tested area. In the present study, we sought to determine the capacity of elderly subjects to resolve such grating stimuli in order to obtain normative data for this population. Thirty-two elderly individuals in good health (range: 60-88 years) were assessed for their ability to perceive grating orientation at the tip of the dominant index finger. Testing proceeded from the widest grating dome (3 mm) to the next (e.g., 2 mm), until the performance level dropped below 75% correct discrimination. The grating orientation task proved to be very difficult for most subjects and only a minority (14/32) was able to provide reliable reports of grating orientation even with presentation of the widest dome available (3 mm). Accordingly, individual grating resolution thresholds were often considerably higher (> 2.5 mm, n = 26) than values previously reported in young adults for the fingertip region (approximately 1 mm). These results suggest that the current set of grating domes may not be adequate for spatial acuity measurement at the fingertip of older adults. New larger grating dimensions should be added to the set presently available to improve their sensitivity for an older population.     

Brightness induction: rate enhancement and neuronal synchronization as complementary codes

In cat visual cortex, we investigated with parallel recordings from multiple units the neuronal correlates of perceived brightness. The perceived brightness of a center grating was changed by varying the orientation or the relative spatial phase of a surrounding grating. Brightness enhancement by orientation contrast is associated with an increase of discharge rates of responses to the center grating but not with changes in spike synchronization. In contrast, if brightness enhancement is induced by phase offset, discharge rates are unchanged but synchronization increases between neurons responding to the center grating. The changes in synchronization correlate well with changes in perceived brightness that were assessed in parallel in human subjects using the same stimuli. These results indicate that in cerebral cortex the modulation of synchronicity of responses is used as a mechanism complementary to rate changes to enhance the saliency of neuronal responses.     

Cooperative activity of DNA methyltransferases for maintenance of symmetrical and non-symmetrical cytosine methylation in Arabidopsis thaliana

Maintenance of cytosine methylation in plants is controlled by three DNA methyltransferases. MET1 maintains CG methylation, and DRM1/2 and CMT3 act redundantly to enforce non-CG methylation. RPS, a repetitive hypermethylated DNA fragment from Petunia hybrida, attracts DNA methylation when transferred into Petunia or other species. In Arabidopsis thaliana, which does not contain any RPS homologues, RPS transgenes are efficiently methylated in all sequence contexts. To test which DNA methylation pathways regulate RPS methylation, we examined maintenance of RPS methylation in various mutant backgrounds. Surprisingly, CG methylation was lost in a drm1/2/cmt3 mutant, and non-CG methylation was almost completely eliminated in a met1 mutant. An unusual cooperative activity of all three DNA methyltransferases is therefore required for maintenance of both CG and non-CG methylation in RPS. Other unusual features of RPS methylation are the independence of its non-CG methylation from the RNA-directed DNA methylation (RdDM) pathway and the exceptional maintenance of methylation at a CC(m)TGG site in some epigenetic mutants. This is indicative of activity of a methylation system in plants that may have evolved from the DCM methylation system that controls CC(m)WGG methylation in bacteria. Our data suggest that strict separation of CG and non-CG methylation pathways does not apply to all target regions, and that caution is required in generalizing methylation data obtained for individual genomic regions.     

Detection of sinusoidal gratings by pattern-specific detectors: further evidence for the correlation principle in human vision

 The detection of compound sinusoidal gratings of various spatial frequency separations and four different grating sizes has been studied using the summation-to-threshold paradigm. Contrast interrelation functions have been measured and spatial frequency tuning estimates, based on the slope of the contrast interrelation function at two definite points, were derived using the “negative gradient technique” proposed by Logvinenko [Logvinenko (1995) Biol Cybern 73: 547–552]. It is shown that compound grating detection can be modelled by assuming pattern-specific sensory mechanisms for each of the spatial frequency components, which adapt to the periodicity and the size of the stimulus but not to its envelope function. Further, it is shown that relative sensitivity for a given spatial frequency separation can be predicted with good accuracy by the correlation of the grating components used for superposition. It is suggested that the most plausible implementation of the pattern correlation principle in human grating detection is the “grating cell” model. Received: 10 March 2000 / Accepted in revised form: 4 December 2000