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

Minho affective sentences (MAS): probing the roles of sex, mood, and empathy in affective ratings of verbal stimuli

Author's personal copyDuring social communication, words and sentences play a critical role in the expression of emotional meaning. The Minho Affective Sentences (MAS) were developed to respond to the lack of a standardized sentences battery with normative affective ratings: 192 neutral, positive, and negative declarative sentences were strictly controlled for psycholinguistic variables such as number of words and letters, and per million word frequency. The sentences were designed to represent examples of each of the five basic emotions (anger, sadness, disgust, fear, happiness) and of neutral situations. These sentences were presented to 536 participants who rated the stimuli using both dimensional and categorical measures of emotions. Sex differences were also explored. Additionally, we probed how personality, empathy and mood from a sub-set of 40 participants modulated the affective ratings. Our results confirmed that the MAS affective norms are valid measures to guide the selection of stimuli for experimental studies of emotion. The combination of dimensional and categorical ratings provided a more fine-grained characterization of the affective properties of sentences. Moreover, affective ratings of positive and negative sentences were not only modulated by participant’s sex, but also by individual differences in empathy and mood state.Together, our results indicate that, in their quest to reveal the neuro-functional underpinnings of verbal emotional processing, researchers should consider not only the influence of sex, but also of inter-individual differences in empathy and mood states, in the response to the emotional meaning of sentences.The authors gratefully acknowledge all the participants who collaborated in the study, and Vera Matos for her help with data acquisition. This work was supported by Grant Numbers IF/00334/2012 and PTDC/MHNPCN/3606/2012, funded by the Portuguese National Science Foundation (Fundação para a Ciência e a Tecnologia [FCT], Portugal) and FEDER (Fundo Europeu de Desenvolvimento Regional) through the European programs QREN (Quadro de Referência Estratégico Nacional) and COMPETE (Programa Operacional Factores de Competitividade), awarded to A.P.P. Additionally, it received support from Grant Number EXPL/MHCPCN/0859/2013, awarded to A.P.S. by FCT and cofunded by FEDER under the PT2020 Partnership Agreement.info:eu-repo/semantics/publishedVersio

Erratum: Searches for continuous gravitational waves from nine young supernova remnants (2015, ApJ, 813, 39)

We describe directed searches for continuous gravitational waves in data from the sixth LIGO science data run. The targets were nine young supernova remnants not associated with pulsars; eight of the remnants are associated with non-pulsing suspected neutron stars. One target's parameters are uncertain enough to warrant two searches, for a total of ten. Each search covered a broad band of frequencies and first and second frequency derivatives for a fixed sky direction. The searches coherently integrated data from the two LIGO interferometers over time spans from 5.3-25.3 days using the matched-filtering F-statistic. We found no credible gravitational-wave signals. We set 95% confidence upper limits as strong (low) as $4\times10^{-25}$ on intrinsic strain, $2\times10^{-7}$ on fiducial ellipticity, and $4\times10^{-5}$ on r-mode amplitude. These beat the indirect limits from energy conservation and are within the range of theoretical predictions for neutron-star ellipticities and r-mode amplitudes