SuperFreq: Integrated mutation detection and clonal tracking in cancer.

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

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

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

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

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

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

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

Polycomb Repressive Complex 2 (PRC2) Restricts Hematopoietic Stem Cell Activity

Polycomb group proteins are transcriptional repressors that play a central role in the establishment and maintenance of gene expression patterns during development. Using mice with an N-ethyl-N-nitrosourea (ENU)-induced mutation in Suppressor of Zeste 12 (Suz12), a core component of Polycomb Repressive Complex 2 (PRC2), we show here that loss of Suz12 function enhances hematopoietic stem cell (HSC) activity. In addition to these effects on a wild-type genetic background, mutations in Suz12 are sufficient to ameliorate the stem cell defect and thrombocytopenia present in mice that lack the thrombopoietin receptor (c-Mpl). To investigate the molecular targets of the PRC2 complex in the HSC compartment, we examined changes in global patterns of gene expression in cells deficient in Suz12. We identified a distinct set of genes that are regulated by Suz12 in hematopoietic cells, including eight genes that appear to be highly responsive to PRC2 function within this compartment. These data suggest that PRC2 is required to maintain a specific gene expression pattern in hematopoiesis that is indispensable to normal stem cell function

Longer First Introns Are a General Property of Eukaryotic Gene Structure

While many properties of eukaryotic gene structure are well characterized, differences in the form and function of introns that occur at different positions within a transcript are less well understood. In particular, the dynamics of intron length variation with respect to intron position has received relatively little attention. This study analyzes all available data on intron lengths in GenBank and finds a significant trend of increased length in first introns throughout a wide range of species. This trend was found to be even stronger when using high-confidence gene annotation data for three model organisms (Arabidopsis thaliana, Caenorhabditis elegans, and Drosophila melanogaster) which show that the first intron in the 5′ UTR is - on average - significantly longer than all downstream introns within a gene. A partial explanation for increased first intron length in A. thaliana is suggested by the increased frequency of certain motifs that are present in first introns. The phenomenon of longer first introns can potentially be used to improve gene prediction software and also to detect errors in existing gene annotations

Crop Updates 2007 - Cereals

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

Germline MBD4-deficiency causes a multi-tumor predisposition syndrome

We report an autosomal recessive, multi-organ tumor predisposition syndrome, caused by bi-allelic loss-of-function germline variants in the base excision repair (BER) gene MBD4. We identified five individuals with bi-allelic MBD4 variants within four families and these individuals had a personal and/or family history of adenomatous colorectal polyposis, acute myeloid leukemia, and uveal melanoma. MBD4 encodes a glycosylase involved in repair of G:T mismatches resulting from deamination of 5′-methylcytosine. The colorectal adenomas from MBD4-deficient individuals showed a mutator phenotype attributable to mutational signature SBS1, consistent with the function of MBD4. MBD4-deficient polyps harbored somatic mutations in similar driver genes to sporadic colorectal tumors, although AMER1 mutations were more common and KRAS mutations less frequent. Our findings expand the role of BER deficiencies in tumor predisposition. Inclusion of MBD4 in genetic testing for polyposis and multi-tumor phenotypes is warranted to improve disease management