Copy number variation analysis based on AluScan sequences

BACKGROUND: AluScan combines inter-Alu PCR using multiple Alu-based primers with opposite orientations and next-generation sequencing to capture a huge number of Alu-proximal genomic sequences for investigation. Its requirement of only sub-microgram quantities of DNA facilitates the examination of large numbers of samples. However, the special features of AluScan data rendered difficult the calling of copy number variation (CNV) directly using the calling algorithms designed for whole genome sequencing (WGS) or exome sequencing. RESULTS: In this study, an AluScanCNV package has been assembled for efficient CNV calling from AluScan sequencing data employing a Geary-Hinkley transformation (GHT) of read-depth ratios between either paired test-control samples, or between test samples and a reference template constructed from reference samples, to call the localized CNVs, followed by use of a GISTIC-like algorithm to identify recurrent CNVs and circular binary segmentation (CBS) to reveal large extended CNVs. To evaluate the utility of CNVs called from AluScan data, the AluScans from 23 non-cancer and 38 cancer genomes were analyzed in this study. The glioma samples analyzed yielded the familiar extended copy-number losses on chromosomes 1p and 9. Also, the recurrent somatic CNVs identified from liver cancer samples were similar to those reported for liver cancer WGS with respect to a striking enrichment of copy-number gains in chromosomes 1q and 8q. When localized or recurrent CNV-features capable of distinguishing between liver and non-liver cancer samples were selected by correlation-based machine learning, a highly accurate separation of the liver and non-liver cancer classes was attained. CONCLUSIONS: The results obtained from non-cancer and cancerous tissues indicated that the AluScanCNV package can be employed to call localized, recurrent and extended CNVs from AluScan sequences. Moreover, both the localized and recurrent CNVs identified by this method could be subjected to machine-learning selection to yield distinguishing CNV-features that were capable of separating between liver cancers and other types of cancers. Since the method is applicable to any human DNA sample with or without the availability of a paired control, it can also be employed to analyze the constitutional CNVs of individuals.published_or_final_versio

A Herschel study of NGC 650

As part of the Herschel guaranteed time key project Mass loss of Evolved StarS (MESS) we have imaged a sample of planetary nebulae. In this paper we present the Photodetector Array Camera and Spectrometer (PACS) and Spectral and Photometric Imaging Receiver (SPIRE) images of the classical bipolar planetary nebula NGC 650. We used these images to derive a temperature map of the dust. We also constructed a photoionization and dust radiative transfer model using the spectral synthesis code Cloudy. To constrain this model, we used the PACS and SPIRE fluxes and combined them with hitherto unpublished International Ultraviolet Explorer (IUE) and Spitzer InfraRed Spectrograph (IRS) spectra as well as various other data from the literature. A temperature map combined with a photoionization model were used to study various aspects of the central star, the nebula, and in particular the dust grains in the nebula. The central star parameters are determined to be Teff = 208 kK and L = 261 L⊙ assuming a distance of 1200 pc. The stellar temperature is much higher than previously published values. We confirm that the nebula is carbon-rich with a C/O ratio of 2.1. The nebular abundances are typical for a type IIa planetary nebula. With the photoionization model we determined that the grains in the ionized nebula are large (assuming single-sized grains, they would have a radius of 0.15 μm). Most likely these large grains were inherited from the asymptotic giant branch phase. The PACS 70/160 μm temperature map shows evidence of two radiation components heating the grains. The first component is direct emission from the central star, while the second component is diffuse emission from the ionized gas (mainly Lyα). We show that previous suggestions of a photo-dissociation region surrounding the ionized region are incorrect. The neutral material resides in dense clumps inside the ionized region. These may also harbor stochastically heated very small grains in addition to the large grains

Genetic Code Mutations: The Breaking of a Three Billion Year Invariance

The genetic code has been unchanging for some three billion years in its canonical ensemble of encoded amino acids, as indicated by the universal adoption of this ensemble by all known organisms. Code mutations beginning with the encoding of 4-fluoro-Trp by Bacillus subtilis, initially replacing and eventually displacing Trp from the ensemble, first revealed the intrinsic mutability of the code. This has since been confirmed by a spectrum of other experimental code alterations in both prokaryotes and eukaryotes. To shed light on the experimental conversion of a rigidly invariant code to a mutating code, the present study examined code mutations determining the propagation of Bacillus subtilis on Trp and 4-, 5- and 6-fluoro-tryptophans. The results obtained with the mutants with respect to cross-inhibitions between the different indole amino acids, and the growth effects of individual nutrient withdrawals rendering essential their biosynthetic pathways, suggested that oligogenic barriers comprising sensitive proteins which malfunction with amino acid analogues provide effective mechanisms for preserving the invariance of the code through immemorial time, and mutations of these barriers open up the code to continuous change

Herschel imaging of the dust in the Helix nebula (NGC 7293)

Aims. In our series of papers presenting the Herschel imaging of evolved planetary nebulae, we present images of the dust distribution in the Helix nebula (NGC 7293). / Methods. Images at 70, 160, 250, 350, and 500 μm were obtained with the PACS and SPIRE instruments on board the Herschel satellite. / Results. The broadband maps show the dust distribution over the main Helix nebula to be clumpy and predominantly present in the barrel wall. We determined the spectral energy distribution of the main nebula in a consistent way using Herschel, IRAS, and Planck flux values. The emissivity index of β = 0.99 ± 0.09, in combination with the carbon rich molecular chemistry of the nebula, indicates that the dust consists mainly of amorphous carbon. The dust excess emission from the central star disk is detected at 70 μm and the flux measurement agrees with previous measurement. We present the temperature and dust column density maps. The total dust mass across the Helix nebula (without its halo) is determined to be 3.5 × 10-3 M⊙ at a distance of 216 pc. The temperature map shows dust temperatures between 22 K and 42 K, which is similar to the kinetic temperature of the molecular gas, confirming that the dust and gas co-exist in high density clumps. Archived images are used to compare the location of the dust emission in the far infrared (Herschel) with the ionized (GALEX and Hβ) and molecular (H2) component. The different emission components are consistent with the Helix consisting of a thick walled barrel-like structure inclined to the line of sight. The radiation field decreases rapidly through the barrel wall

Herschel images of NGC 6720: H-2 formation on dust grains

Herschel PACS and SPIRE images have been obtained of NGC 6720 (the Ring nebula). This is an evolved planetary nebula with a central star that is currently on the cooling track, due to which the outer parts of the nebula are recombining. From the PACS and SPIRE images we conclude that there is a striking resemblance between the dust distribution and the H2 emission, which appears to be observational evidence that H2 forms on grain surfaces. We have developed a photoionization model of the nebula with the Cloudy code which we used to determine the physical conditions of the dust and investigate possible formation scenarios for the H2. We conclude that the most plausible scenario is that the H2 resides in high density knots which were formed after the recombination of the gas started when the central star entered the cooling track. Hydrodynamical instabilities due to the unusually low temperature of the recombining gas are proposed as a mechanism for forming the knots. H2 formation in the knots is expected to be substantial after the central star underwent a strong drop in luminosity about one to two thousand years ago, and may still be ongoing at this moment, depending on the density of the knots and the properties of the grains in the knots

Detection of anhydrous hydrochloric acid, HCl, in IRC+10216 with the Herschel SPIRE and PACS spectrometers Detection of HCI in IRC+10216

We report on the detection of anhydrous hydrochloric acid (hydrogen chlorine, HCl) in the carbon-rich star IRC +10216 using the spectroscopic facilities onboard the Herschel satellite. Lines from J = 1–0 up to J = 7–6 have been detected. From the observed intensities, we conclude that HCl is produced in the innermost layers of the circumstellar envelope with an abundance relative to H2 of 5 × 10-8 and extends until the molecules reach its photodissociation zone. Upper limits to the column densities of AlH, MgH, CaH, CuH, KH, NaH, FeH, and other diatomic hydrides have also been obtained

Silicon in the dust formation zone of IRC +10216 as observed with PACS and SPIRE on board Herschel

The interstellar medium is enriched primarily by matter ejected from evolved low and intermediate mass stars. The outflows from these stars create a circumstellar envelope in which a rich gas-phase and dust-nucleation chemistry takes place. We observed the nearest carbon-rich evolved star, IRC+10216, using the PACS (55-210 {\mu}m) and SPIRE (194-672 {\mu}m) spectrometers on board Herschel. We find several tens of lines from SiS and SiO, including lines from the v=1 vibrational level. For SiS these transitions range up to J=124-123, corresponding to energies around 6700K, while the highest detectable transition is J=90-89 for SiO, which corresponds to an energy around 8400K. Both species trace the dust formation zone of IRC+10216, and the broad energy ranges involved in their detected transitions permit us to derive the physical properties of the gas and the particular zone in which each species has been formed. This allows us to check the accuracy of chemical thermodynamical equilibrium models and the suggested depletion of SiS and SiO due to accretion onto dust grains

Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs

Delivering in‐school interventions to improve dietary behaviours amongst 11‐ to 16‐year‐olds: A systematic review

Childhood obesity is a global health concern, which has both short‐and long‐term health consequences for the individual, and is a potential burden on health care services and the wider economy. The school environment is a setting where changes can be applied to dietary behaviours, as schools have direct and intensive contact with children. This systematic review evaluated school‐based interventions designed to improve dietary behaviours among adolescents (11‐to 16‐year‐olds). The aims were to review types of interventions delivered, dietary behaviours targeted, and interventions' effectiveness in improving dietary behaviour and associated intervention components. Twenty‐nine school‐based interventional studies with this population were identified for review. The data were synthesized by identifying and comparing individual studies' results, intervention components, and characteristics.Interventions appeared more effective when they involved peers, used educational media to deliver health messages, increased availability of healthy foods in school,and incorporated computer‐based individualized feedback with normative information on eating behaviours. A limitation of the review was the lack of description in cer-tain reviewed studies and the nonfeasibility of conducting a meta‐analysis owing to study heterogeneity. Future interventions with this population could consider including the aforementioned components, gender‐specific feedback, and both short‐and long‐term follow‐ups as change may not be apparent immediately and to determine if changes are sustained