141 research outputs found

    SuperFreq: Integrated mutation detection and clonal tracking in cancer.

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    Analysing multiple cancer samples from an individual patient can provide insight into the way the disease evolves. Monitoring the expansion and contraction of distinct clones helps to reveal the mutations that initiate the disease and those that drive progression. Existing approaches for clonal tracking from sequencing data typically require the user to combine multiple tools that are not purpose-built for this task. Furthermore, most methods require a matched normal (non-tumour) sample, which limits the scope of application. We developed SuperFreq, a cancer exome sequencing analysis pipeline that integrates identification of somatic single nucleotide variants (SNVs) and copy number alterations (CNAs) and clonal tracking for both. SuperFreq does not require a matched normal and instead relies on unrelated controls. When analysing multiple samples from a single patient, SuperFreq cross checks variant calls to improve clonal tracking, which helps to separate somatic from germline variants, and to resolve overlapping CNA calls. To demonstrate our software we analysed 304 cancer-normal exome samples across 33 cancer types in The Cancer Genome Atlas (TCGA) and evaluated the quality of the SNV and CNA calls. We simulated clonal evolution through in silico mixing of cancer and normal samples in known proportion. We found that SuperFreq identified 93% of clones with a cellular fraction of at least 50% and mutations were assigned to the correct clone with high recall and precision. In addition, SuperFreq maintained a similar level of performance for most aspects of the analysis when run without a matched normal. SuperFreq is highly versatile and can be applied in many different experimental settings for the analysis of exomes and other capture libraries. We demonstrate an application of SuperFreq to leukaemia patients with diagnosis and relapse samples

    The Carnegie Astrometric Planet Search Program

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    We are undertaking an astrometric search for gas giant planets and brown dwarfs orbiting nearby low mass dwarf stars with the 2.5-m du Pont telescope at the Las Campanas Observatory in Chile. We have built two specialized astrometric cameras, the Carnegie Astrometric Planet Search Cameras (CAPSCam-S and CAPSCam-N), using two Teledyne Hawaii-2RG HyViSI arrays, with the cameras' design having been optimized for high accuracy astrometry of M dwarf stars. We describe two independent CAPSCam data reduction approaches and present a detailed analysis of the observations to date of one of our target stars, NLTT 48256. Observations of NLTT 48256 taken since July 2007 with CAPSCam-S imply that astrometric accuracies of around 0.3 milliarcsec per hour are achievable, sufficient to detect a Jupiter-mass companion orbiting 1 AU from a late M dwarf 10 pc away with a signal-to-noise ratio of about 4. We plan to follow about 100 nearby (primarily within about 10 pc) low mass stars, principally late M, L, and T dwarfs, for 10 years or more, in order to detect very low mass companions with orbital periods long enough to permit the existence of habitable, Earth-like planets on shorter-period orbits. These stars are generally too faint and red to be included in ground-based Doppler planet surveys, which are often optimized for FGK dwarfs. The smaller masses of late M dwarfs also yield correspondingly larger astrometric signals for a given mass planet. Our search will help to determine whether gas giant planets form primarily by core accretion or by disk instability around late M dwarf stars.Comment: 48 pages, 9 figures. in press, Publ. Astron. Soc. Pacifi

    Characterizing the Chemistry of the Milky Way Stellar Halo: Detailed Chemical Analysis of a Metal-Poor Stellar Stream

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    We present the results of a detailed abundance analysis of one of the confirmed building blocks of the Milky Way stellar halo, a kinematically-coherent metal-poor stellar stream. We have obtained high resolution and high S/N spectra of 12 probable stream members using the MIKE spectrograph on the Magellan-Clay Telescope at Las Campanas Observatory and the 2dCoude spectrograph on the Smith Telescope at McDonald Observatory. We have derived abundances or upper limits for 51 species of 46 elements in each of these stars. The stream members show a range of metallicity (-3.4 < [Fe/H] < -1.5) but are otherwise chemically homogeneous, with the same star-to-star dispersion in [X/Fe] as the rest of the halo. This implies that, in principle, a significant fraction of the Milky Way stellar halo could have formed from accreted systems like the stream. The stream stars show minimal evolution in the alpha or Fe-group elements over the range of metallicity. This stream is enriched with material produced by the main and weak components of the rapid neutron-capture process and shows no evidence for enrichment by the slow neutron-capture process.Comment: v2: Removed references to M15 after learning that the source kinematic data for M15 were incorrect in an earlier paper. M15 is not related to this stream. (ApJ, accepted; 31 pages, 18 figures, 11 tables

    Withdrawal periods after treatment of pigs with oxytetracycline in- and outside the European Union

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    Withdrawal periods are used to avoid animals being delivered to slaughter before the concentration of the antimicrobial has declined to values below the maximum residue limit (MRL). This paper characterises the withdrawal periods in force for oxytetracycline 100 mg/ml for intramuscular use in pigs. We investigated the variation in duration of the withdrawal period between 68 oxytetracycline products from 29 countries in- and outside the European Union. More specifically, we tested whether there is a regional difference, a difference between major and minor pig meat exporting countries, whether the product is long-acting or not, and whether year of market authorisation correlated with the withdrawal period. The results showed a large variation in duration of the withdrawal periods, ranging from 5 to 40 days. Variation was observed both between and within countries. Moreover, major exporting countries were associated with a longer withdrawal period than minor exporting countries (P = 0.00099). There were no regional differences, and the year of market authorisation had no impact, but long-acting products had a shorter withdrawal period than short-acting products (P = 0.048). The variation in withdrawal periods observed questions the utility of using compliance with the withdrawal period as a means of assessing whether the meat is safe for consumption. This is particularly relevant when a pig producer unintentionally delivers pigs for slaughter before the withdrawal period has expired and, aware of this, informs the abattoir. The findings call for further harmonisation in determining the withdrawal periods for all veterinary medicinal products (VMP). Until this happens, if animals are prematurely sent to slaughter, we suggest that the concentration of the VMP at the time of slaughter is calculated and compared with the MRL to determine meat safety

    ChIP-seq analysis reveals distinct H3K27me3 profiles that correlate with transcriptional activity

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    Transcriptional control is dependent on a vast network of epigenetic modifications. One epigenetic mark of particular interest is tri-methylation of lysine 27 on histone H3 (H3K27me3), which is catalysed and maintained by Polycomb Repressive Complex 2 (PRC2). Although this histone mark is studied widely, the precise relationship between its local pattern of enrichment and regulation of gene expression is currently unclear. We have used ChIP-seq to generate genome-wide maps of H3K27me3 enrichment, and have identified three enrichment profiles with distinct regulatory consequences. First, a broad domain of H3K27me3 enrichment across the body of genes corresponds to the canonical view of H3K27me3 as inhibitory to transcription. Second, a peak of enrichment around the transcription start site (TSS) is commonly associated with ‘bivalent’ genes, where H3K4me3 also marks the TSS. Finally and most surprisingly, we identified an enrichment profile with a peak in the promoter of genes that is associated with active transcription. Genes with each of these three profiles were found in different proportions in each of the cell types studied. The data analysis techniques developed here will be useful for the identification of common enrichment profiles for other histone modifications that have important consequences for transcriptional regulation

    BRCA1-like signature in triple negative breast cancer: Molecular and clinical characterization reveals subgroups with therapeutic potential.

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    Triple negative (TN) breast cancers make up some 15% of all breast cancers. Approximately 10-15% are mutant for the tumor suppressor, BRCA1. BRCA1 is required for homologous recombination-mediated DNA repair and deficiency results in genomic instability. BRCA1-mutated tumors have a specific pattern of genomic copy number aberrations that can be used to classify tumors as BRCA1-like or non-BRCA1-like. BRCA1 mutation, promoter methylation, BRCA1-like status and genome-wide expression data was determined for 112 TN breast cancer samples with long-term follow-up. Mutation status for 21 known DNA repair genes and PIK3CA was assessed. Gene expression and mutation frequency in BRCA1-like and non-BRCA1-like tumors were compared. Multivariate survival analysis was performed using the Cox proportional hazards model. BRCA1 germline mutation was identified in 10% of patients and 15% of tumors were BRCA1 promoter methylated. Fifty-five percent of tumors classified as BRCA1-like. The functions of genes significantly up-regulated in BRCA1-like tumors included cell cycle and DNA recombination and repair. TP53 was found to be frequently mutated in BRCA1-like (P < 0.05), while PIK3CA was frequently mutated in non-BRCA1-like tumors (P < 0.05). A significant association with worse prognosis was evident for patients with BRCA1-like tumors (adjusted HR = 3.32, 95% CI = 1.30-8.48, P = 0.01). TN tumors can be further divided into two major subgroups, BRCA1-like and non-BRCA1-like with different mutation and expression patterns and prognoses. Based on these molecular patterns, subgroups may be more sensitive to specific targeted agents such as PI3K or PARP inhibitors

    The Ninth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the SDSS-III Baryon Oscillation Spectroscopic Survey

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    The Sloan Digital Sky Survey III (SDSS-III) presents the first spectroscopic data from the Baryon Oscillation Spectroscopic Survey (BOSS). This ninth data release (DR9) of the SDSS project includes 535,995 new galaxy spectra (median z=0.52), 102,100 new quasar spectra (median z=2.32), and 90,897 new stellar spectra, along with the data presented in previous data releases. These spectra were obtained with the new BOSS spectrograph and were taken between 2009 December and 2011 July. In addition, the stellar parameters pipeline, which determines radial velocities, surface temperatures, surface gravities, and metallicities of stars, has been updated and refined with improvements in temperature estimates for stars with T_eff<5000 K and in metallicity estimates for stars with [Fe/H]>-0.5. DR9 includes new stellar parameters for all stars presented in DR8, including stars from SDSS-I and II, as well as those observed as part of the SDSS-III Sloan Extension for Galactic Understanding and Exploration-2 (SEGUE-2). The astrometry error introduced in the DR8 imaging catalogs has been corrected in the DR9 data products. The next data release for SDSS-III will be in Summer 2013, which will present the first data from the Apache Point Observatory Galactic Evolution Experiment (APOGEE) along with another year of data from BOSS, followed by the final SDSS-III data release in December 2014.Comment: 9 figures; 2 tables. Submitted to ApJS. DR9 is available at http://www.sdss3.org/dr

    The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

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    The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

    Crop Updates 2007 - Cereals

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    This session covers twenty six papers from different authors: CEREAL BREEDING 1. Strategies for aligning producer and market imperatives in cereal breeding in Western Australia, R. Loughman, R. Lance, I. Barclay, G. Crosbie, S. Harasymow, W. Lambe, C. Li, R. McLean, C. Moore, K. Stefanova, A. Tarr and R. Wilson, Department of Agriculture and Food 2. LongReach plant breeders wheat variety trials – 2006, Matu Peipi and Matt Whiting, LongReach Plant Breeders WHEAT AGRONOMY 3. Response of wheat varieties to sowing time in the northern agricultural region in 2006, Christine Zaicou, Department of Agriculture and Food 4. Response of wheat varieties to sowing time in the central agricultural region in 2006, Shahajahan Miyan, Department of Agriculture and Food 5. Response of wheat varieties to sowing time in the Great Southern and Lakes region, Brenda Shackleyand Ian Hartley, Department of Agriculture and Food 6. Response of wheat varieties to time of sowing time in Esperance region in 2006, Christine Zaicou, Ben Curtis and Ian Hartley, Department of Agriculture and Food 7. Performance of wheat varieties in National Variety Testing (NVT) WA: Year 2, Peter Burgess, Agritech Crop Research 8. Flowering dates of wheat varieties in Western Australia in 2006, Darshan Sharma, Brenda Shackley and Christine Zaicou, Department of Agriculture and Food 9. Prospects for perennial wheat: A feasibility study, Len J. Wade, Lindsay W. Bell, Felicity Byrne (nee Flugge) and Mike A. Ewing, School of Plant Biology and CRC for Plant-based Management of Dryland Salinity, The University of Western Australia BARLEY AGRONOMY 10. Barley agronomy highlights: Time of sowing x variety, Blakely Paynter and Andrea Hills, Department of Agriculture and Food 11. Barley agronomy highlights: Weeds and row spacing, Blakely Paynter and Andrea Hills, Department of Agriculture and Food 12. Barley agronomy highlights: Weeds and barley variety, Blakely Paynter and Andrea Hills, Department of Agriculture and Food OAT AGRONOMY 13. Agronomic performance of dwarf potential milling oat varieties in varied environments of WA, Raj Malik, Blakely Paynter and Kellie Winfield, Department of Agriculture and Food 14. Sourcing oat production information in 2007, Kellie Winfield, Department of Agriculture and Food HERBICIDE TOLERANCE 15. Response of new wheat varieties to herbicides, Harmohinder Dhammu, Department of Agriculture and Food 16. Herbicide tolerance of new barley varieties, Harmohinder Dhammu, Vince Lambert and Chris Roberts, Department of Agriculture and Food 17. Herbicide tolerance of new oat varieties, Harmohinder Dhammu, Vince Lambert and Chris Roberts, Department of Agriculture and Food NUTRITION 18. Nitrogen Decision Tools – choose your weapon, Jeremy Lemon, Department of Agriculture and Food DISEASES 19. Barley agronomy highlights: Canopy management, Andrea Hills and Blakely Paynter, Department of Agriculture and Food 20. Barley agronomy highlights: Leaf diseases and spots, Andrea Hills and Blakely Paynter, Department of Agriculture and Food 21. Fungicide applications for stripe rust management in adult plant resistant (APR) wheat varieties, Geoff Thomas, Rob Loughman, Ian Hartley and Andrew Taylor; Department of Agriculture and Food 22. Effect of seed treatment with Jockey on time of onset and disease severity of stripe rust in wheat, Manisha Shankar, John Majewski and Rob Loughman, Department of Agriculture and Food 23. Rotations for management of Cereal Cyst Nematode, Vivien Vanstone, Department of Agriculture and Food 24. Occurrence of Wheat Streak Mosaic Virus in Western Australian grainbelt during the 2006 growing season, Brenda Coutts, Monica Kehoe and Roger Jones, Department of Agriculture and Food 25. Development of a seed test for Wheat Streak Mosaic Virus in bulk samples of wheat, Geoffrey Dwyer, Belinda Welsh, Cuiping Wang and Roger Jones, Department of Agriculture and Food MARKETS 26. Developing the Australian barley value chain, Linda Price, Barley Australi
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