CoNVEX: Copy number variation estimation in exome sequencing data using HMM

Background One of the main types of genetic variations in cancer is Copy Number Variations (CNV). Whole exome sequenicng (WES) is a popular alternative to whole genome sequencing (WGS) to study disease specific genomic variations. However, finding CNV in Cancer samples using WES data has not been fully explored. Results We present a new method, called CoNVEX, to estimate copy number variation in whole exome sequencing data. It uses ratio of tumour and matched normal average read depths at each exonic region, to predict the copy gain or loss. The useful signal produced by WES data will be hindered by the intrinsic noise present in the data itself. This limits its capacity to be used as a highly reliable CNV detection source. Here, we propose a method that consists of discrete wavelet transform (DWT) to reduce noise. The identification of copy number gains/losses of each targeted region is performed by a Hidden Markov Model (HMM). Conclusion HMM is frequently used to identify CNV in data produced by various technologies including Array Comparative Genomic Hybridization (aCGH) and WGS. Here, we propose an HMM to detect CNV in cancer exome data. We used modified data from 1000 Genomes project to evaluate the performance of the proposed method. Using these data we have shown that CoNVEX outperforms the existing methods significantly in terms of precision. Overall, CoNVEX achieved a sensitivity of more than 92% and a precision of more than 50%

Comparative Analysis of Deoxynivalenol Biosynthesis Related Gene Expression among Different Chemotypes of Fusarium graminearum in Spring Wheat

Fusarium mycotoxins, deoxynivalenol (DON) and nivalenol (NIV) act as virulence factors and are essential for symptom development after initial infection in wheat. To date, 16 genes have been identified in the deoxynivalenol biosynthesis pathway. However, a comparative gene expression analysis in different chemotypes of F. graminearum in response to fusarium head blight (FHB) infection remains to be explored. Therefore, in this study, nine genes that involved in trichothecene biosynthesis were analysed among 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON) and nivalenol (NIV) producing F. graminearum strains in a time course study. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) revealed that the expression of all examined TRI gene transcripts initiated at two days post-inoculation (dpi), peaked at three to four dpi and gradually decreased at seven dpi. The early induction of TRI genes indicates that presence of high levels of TRI gene transcripts at early stages, is important to initiate the biosynthetic pathway of DON and NIV. Comparison of gene expression among the three chemotypes showed that relative expression of TRI genes was higher in 3-ADON producing strains compared with 15-ADON and NIV strains. Comparatively higher levels of gene expression may contribute to the higher levels of DON produced by 3-ADON strains in infected grains

BLOOD RESPIRATORY PARAMETERS IN THREE SPECIES OF CULTIVATED FISH

The study was oarried out on three species of fish which are commerciallyimportant and presently cultivated in Sri Lanka. These are Oreochromismossambicus, Oreochromis niloticus and Chanos chanos. Blood parametersmeasured in the resting state for the three species were haematocrit, erythrocytecounts and haemoglobin concentrations. From these findings the followingwere calculated. The Hb content per single erythrocyte, the Hb concentration per single erythrocyte and volume of a single erythrocyte. It wasfound that all these values were higher in the Oreochromis species comparedto Chanos. Inverse relationships between erythrocyte count and volume ofa single erythrocyte and between cell count and Hb content per single erythrocyte were observed. O2 capacities and O2 dissociation curves were also determined. The effect of pH on 0. affinity was also studied. In vivo experimentswere conducted to measure rates of 02 consumption in the resting state of fish

Effects of low water PH on some heamatological and physiological parameters of oreochromis mossambicus

In this study tolerance to acid water pollution and the effects of acid waterpollution on some haematological and physiological parameters were investigatedin Oreochromis mossambicus, a species of fish which is well establishedand widely distributed in the inland waters of Sri Lanka. From the tolerancetests it was found that the maximum toleran.ce level, with 100% survivaloccurred at pH 4. Therefore in this study the fish were acclimated to pH(H2So4) 4.0 ± 0.1 for a period of two weeks before the changes in bloodparameters were determined. Water in the control tanks had a pH of 7.0-7.2.Acid exposure caused significant disturbances in haematological parameters.The haematocrit, red blood cell count and haemaglobin concentrationincreased while the three haematological indices; haemaglobin content ofa single erythrocyte, haemaglobin concentration of a single erythrocyte andcell volume of single erythrocyte decreased. The blood pH also decreased.But 02 capacity, 02 consumption, metabolic rate and plasma Na- concentrationremained unaltered.This study reveals that O. mossambicus can tolerate a water pH downto pH 4 with little or no difficulty for extended periods, and is able to regulateits physiolobical status to compensate the body's 02 demands. This is incontrast with reports for many other species whose survival is limited at thislevel of pH

Structure-function analysis of the curli accessory protein CsgE defines surfaces essential for coordinating amyloid fiber formation

Curli amyloid fibers are produced as part of the extracellular biofilm matrix and are composed primarily of the major structural subunit CsgA. The CsgE chaperone facilitates the secretion of CsgA through CsgG by forming a cap at the base of the nonameric CsgG outer membrane pore. We elucidated a series of finely tuned nonpolar and charge-charge interactions that facilitate the oligomerization of CsgE and its ability to transport unfolded CsgA to CsgG for translocation. CsgE oligomerization in vitro is temperature dependent and is disrupted by mutations in the W48 and F79 residues. Using nuclear magnetic resonance (NMR), we identified two regions of CsgE involved in the CsgE-CsgA interaction: a head comprising a positively charged patch centered around R47 and a stem comprising a negatively charged patch containing E31 and E85. Negatively charged residues in the intrinsically disordered N- and C-terminal “tails” were not implicated in this interaction. Head and stem residues were mutated and interrogated using in vivo measurements of curli production and in vitro amyloid polymerization assays. The R47 head residue of CsgE is required for stabilization of CsgA- and CsgE-mediated curli fiber formation. Mutation of the E31 and E85 stem residues to positively charged side chains decreased CsgE-mediated curli fiber formation but increased CsgE-mediated stabilization of CsgA. No single-amino-acid substitutions in the head, stem, or tail regions affected the ability of CsgE to cap the CsgG pore as determined by a bile salt sensitivity assay. These mechanistic insights into the directed assembly of functional amyloids in extracellular biofilms elucidate possible targets for biofilm-associated bacterial infections.Curli represent a class of functional amyloid fibers produced by Escherichia coli and other Gram-negative bacteria that serve as protein scaffolds in the extracellular biofilm matrix. Despite the lack of sequence conservation among different amyloidogenic proteins, the structural and biophysical properties of functional amyloids such as curli closely resemble those of amyloids associated with several common neurodegenerative diseases. These parallels are underscored by the observation that certain proteins and chemicals can prevent amyloid formation by the major curli subunit CsgA and by alpha-synuclein, the amyloid-forming protein found in Lewy bodies during Parkinson’s disease. CsgA subunits are targeted to the CsgG outer membrane pore by CsgE prior to secretion and assembly into fibers. Here, we use biophysical, biochemical, and genetic approaches to elucidate a mechanistic understanding of CsgE function in curli biogenesis

Halide: a language and compiler for optimizing parallelism, locality, and recomputation in image processing pipelines

Image processing pipelines combine the challenges of stencil computations and stream programs. They are composed of large graphs of different stencil stages, as well as complex reductions, and stages with global or data-dependent access patterns. Because of their complex structure, the performance difference between a naive implementation of a pipeline and an optimized one is often an order of magnitude. Efficient implementations require optimization of both parallelism and locality, but due to the nature of stencils, there is a fundamental tension between parallelism, locality, and introducing redundant recomputation of shared values. We present a systematic model of the tradeoff space fundamental to stencil pipelines, a schedule representation which describes concrete points in this space for each stage in an image processing pipeline, and an optimizing compiler for the Halide image processing language that synthesizes high performance implementations from a Halide algorithm and a schedule. Combining this compiler with stochastic search over the space of schedules enables terse, composable programs to achieve state-of-the-art performance on a wide range of real image processing pipelines, and across different hardware architectures, including multicores with SIMD, and heterogeneous CPU+GPU execution. From simple Halide programs written in a few hours, we demonstrate performance up to 5x faster than hand-tuned C, intrinsics, and CUDA implementations optimized by experts over weeks or months, for image processing applications beyond the reach of past automatic compilers.United States. Dept. of Energy (Award DE-SC0005288)National Science Foundation (U.S.) (Grant 0964004)Intel CorporationCognex CorporationAdobe System

Ocean-scale footprint of a highly mobile fishing fleet: Social-ecological drivers of fleet behaviour and evidence of illegal fishing.

Managing the footprint of highly mobile fishing fleets is increasingly important due to continuing declines in fish populations. However, social-ecological drivers for fisher behaviour remain poorly understood for many fleets globally. Using the Sri Lankan fleet as a case study, we explored the role of social, environmental and policy drivers of effort distribution and illegal fishing. We used semi-structured interviews and participatory mapping with 95 fishers, combined with explanatory modelling (GLM) and multivariate statistics, including principal component analysis (PCA). Our findings highlighted the broad footprint (~3,800,000 km2) of this fleet, with fishing effort expended in high seas (53.9%), domestic (40.9%) and, illegally, in foreign waters (5.2%). Twenty-six per cent of fishers directly admitted to fishing illegally in foreign waters during interviews, whereas 62% of fishers indicated doing so during participatory mapping. GLMs explained underlying decisions of where to fish (36% of the total deviance in effort distribution) as a function of social variables (14%), notably distance from landing sites (13%), and environmental variables (11%), notably sea surface temperature (10%). Multivariate analysis revealed that individual fisher characteristics associated with illegal fishing, such as a level of reliance on sharks, vary across the fleet. The analysis of qualitative data suggested that the influence of interpersonal and community social networks and perceptions of higher catch value, particularly of sharks, may be important. Our approach demonstrated the utility of mixed methods research, including the collection of qualitative data, for creating a detailed understanding of spatial behaviour, including decisions of whether to fish illegally. Results highlighted the importance of adopting a social-ecological lens to investigate drivers for human behaviour and non-compliance with rules. We advocate for a nuanced approach to monitoring and managing of fleets, including investigating localised social drivers for illegal fishing and enhancing regional transparency in fleet monitoring

Simulation results for a low energy nuclear recoil yields measurement in liquid xenon using the MiX detector

Measuring the scintillation and ionization yields of liquid xenon in response to ultra-low energy nuclear recoil events is necessary to increase the sensitivity of liquid xenon experiments to light dark matter. Neutron capture on xenon can be used to produce nuclear recoil events with energies below $0.3$ keV$_\text{NR}$ via the asymmetric emission of $\gamma$ rays during nuclear de-excitation. The feasibility of an ultra-low energy nuclear recoil measurement using neutron capture was investigated for the Michigan Xenon (MiX) detector, a small dual-phase xenon time projection chamber that is optimized for a high scintillation gain. Simulations of the MiX detector, a partial neutron moderator, and a pulsed neutron generator indicate that a population of neutron capture events can be isolated from neutron scattering events. Further, the rate of neutron captures in the MiX detector was optimized by varying the thickness of the partial neutron moderator, neutron pulse width, and neutron pulse frequency.Comment: 7 pages, 5 figures. LIDINE 2022 proceeding

Inferring copy number and genotype in tumour exome data

Background: Using whole exome sequencing to predict aberrations in tumours is a cost effective alternative to whole genome sequencing, however is predominantly used for variant detection and infrequently utilised for detection of somatic copy number variation. Results: We propose a new method to infer copy number and genotypes using whole exome data from paired tumour/normal samples. Our algorithm uses two Hidden Markov Models to predict copy number and genotypes and computationally resolves polyploidy/aneuploidy, normal cell contamination and signal baseline shift. Our method makes explicit detection on chromosome arm level events, which are commonly found in tumour samples. The methods are combined into a package named ADTEx (Aberration Detection in Tumour Exome). We applied our algorithm to a cohort of 17 in-house generated and 18 TCGA paired ovarian cancer/normal exomes and evaluated the performance by comparing against the copy number variations and genotypes predicted using Affymetrix SNP 6.0 data of the same samples. Further, we carried out a comparison study to show that ADTEx outperformed its competitors in terms of precision and F-measure. Conclusions: Our proposed method, ADTEx, uses both depth of coverage ratios and B allele frequencies calculated from whole exome sequencing data, to predict copy number variations along with their genotypes. ADTEx is implemented as a user friendly software package using Python and R statistical language. Source code and sample data are freely available under GNU license (GPLv3) at http://adtex.sourceforge.net/