Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Comparative genomic analysis of innate immunity reveals novel and conserved components in crustacean food crop species

Abstract Background Growing global demands for crustacean food crop species have driven large investments in aquaculture research worldwide. However, large-scale production is susceptible to pathogen-mediated destruction particularly in developing economies. Thus, a thorough understanding of the immune system components of food crop species is imperative for research to combat pathogens. Results Through a comparative genomics approach utilising extant data from 55 species, we describe the innate immune system of the class Malacostraca, which includes all food crop species. We identify 7407 malacostracan genes from 39 gene families implicated in different aspects of host defence and demonstrate dynamic evolution of innate immunity components within this group. Malacostracans have achieved flexibility in recognising infectious agents through divergent evolution and expansion of pathogen recognition receptors genes. Antiviral RNAi, Toll and JAK-STAT signal transduction pathways have remained conserved within Malacostraca, although the Imd pathway appears to lack several key components. Immune effectors such as the antimicrobial peptides (AMPs) have unique evolutionary profiles, with many malacostracan AMPs not found in other arthropods. Lastly, we describe four putative novel immune gene families, potentially representing important evolutionary novelties of the malacostracan immune system. Conclusion Our analyses across the broader Malacostraca have allowed us to not only draw analogies with other arthropods but also to identify evolutionary novelties in immune modulation components and form strong hypotheses as to when key pathways have evolved or diverged. This will serve as a key resource for future immunology research in crustacean food crops

Improvement of the thermal stability of sintered Nd-Fe-B magnets by intergranular addition of Dy82.3Co17.7

In this study, microstructure and magnetic properties of sintered Nd-Fe-B magnets with addition of Dy82.3Co17.7 (wt. %) were investigated. By adding a small amount of Dy82.3Co17.7, the coercivity is improved greatly, and the irreversible loss is decreased sharply. The increase of Curie temperature suggests that Co atoms have entered into the 2:14:1 main phase. Microstructural analysis indicates that a well-developed core-shell structure was formed in the magnets with the addition of Dy82.3Co17.7. The improvement of magnetic properties can be attributed to the microstructural modification and the intrinsic properties' improvement. (C) 2014 AIP Publishing LLC

Group Average Difference: A Termination Criterion for Active Contour

This paper presents a termination criterion for active contour that does not involve alteration of the energy functional. The criterion is based on the area difference of the contour during evolution. In this criterion, the evolution of the contour terminates when the area difference fluctuates around a constant. The termination criterion is tested using parametric gradient vector flow active contour with contour resampling and normal force selection. The usefulness of the criterion is shown through its trend, speed, accuracy, shape insensitivity, and insensitivity to contour resampling. The metric used in the proposed criterion demonstrated a steadily decreasing trend. For automatic implementation in which different shapes need to be segmented, the proposed criterion demonstrated almost 50% and 60% total time reduction while achieving similar accuracy as compared with the pixel movement-based method in the segmentation of synthetic and real medical images, respectively. Our results also show that the proposed termination criterion is insensitive to shape variation and contour resampling. The criterion also possesses potential to be used for other kinds of snakes