Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

The (In)visible Hand of the EU : How the EU has affected changes in Turkey's Asylum and Refugee Policy?

Previous literature on the Europeanization of candidate countries has lacked careful empirical investigations into how the process drives domestic policies to change in line with the EU acquis. Selecting on the least-likely case of Turkey and its refugee and asylum policy, I identify that previous work has assumed that Turkey’s policy shifts have been driven by rationalist cost- benefit calculations of its government. The purpose of this study has been to empirically investigate and trace the mechanisms of Europeanization in the selected case, in order to thereby contribute to knowledge on the process of Europeanization in candidate countries in general, and address to the previous research gap. Given this purpose, I have aimed to produce answers to the research question: how has the EU affected Turkey’s asylum and refugee policy after the declaration of candidacy status? I hypothesize that a rationalist model driven by the EU’s conditionality can indeed explain domestic policy changes in Turkey, but also that an alternative mechanism of socialization has been at play. Tracing the process of Europeanization through secondary sources, the results show that what started with behavioral-adaptation of domestic policy change in alignment with the EU’s laws, norms and demands between 1999 and 2010, between 2011 and 2018 the Turkish asylum and refugee policies started to step away from the push power of the external incentives. Nonetheless, significant domestic policy changes continued, suggesting evidence against the rationalist conditionality model of Europeanization in this period. However, I argue that the results are not strong enough to make the claim Turkey’s domestic policy change was driven by a mechanism of socialization, but rather suggest there has been initiation of a switch between the mechanisms.

Organized violence 1989-2020, with a special emphasis on Syria

This article reports on trends in organized violence, building on new data by the Uppsala Conflict Data Program (UCDP). The falling trend in fatalities stemming from organized violence in the world, observed for five consecutive years, broke upwards in 2020 and deaths in organized violence seem to have settled on a high plateau. UCDP registered more than 80,100 deaths in organized violence in 2020, compared to 76,300 in 2019. The decrease in violence in Afghanistan and Syria was countered by escalating conflicts in, for example, Artsakh (Nagorno-Karabakh), Azerbaijan and Tigray, Ethiopia. Moreover, the call for a global ceasefire following the outbreak of the COVID-19 pandemic failed to produce any results. In fact, the number of active state-based and non-state conflicts, as well as the number of actors carrying out one-sided violence against civilians, increased when compared to 2019. UCDP noted a record-high number of 56 state-based conflicts in 2020, including eight wars. Most of the conflicts occurred in Africa, as the region registered 30 state-based conflicts, including nine new or restarted ones

Optical control of magnetization in a room-temperature magnet: V-Cr Prussian blue analog

We report reversible photoinduced magnetic phenomena for a V-Cr Prussian blue analog (T(c) similar to 350 K). This molecule-based magnet exhibits a decrease in magnetization upon illumination with UV light (lambda similar to 350 nm) and reaches a metastable state that has a long lifetime at low temperatures (>10(6) s at 10 K). This photoexcited magnetic state totally recovers back to the ground state by warming above 250 K, and partially recovers with green light (lambda similar to 514 nm) illumination. The effect of green light is triggered only when the sample is previously UV irradiated, suggesting a hidden metastable magnetic state. The photoinduced magnetic effects are proposed to originate from structural distortion that alters the magnetic exchange coupling and/or anisotropy.open11

The RSNA Cervical Spine Fracture CT Dataset.

This dataset is composed of cervical spine CT images with annotations related to fractures; it is available at https://www.kaggle.com/competitions/rsna-2022-cervical-spine-fracture-detection/

The RSNA Cervical Spine Fracture CT Dataset.

This dataset is composed of cervical spine CT images with annotations related to fractures; it is available at https://www.kaggle.com/competitions/rsna-2022-cervical-spine-fracture-detection/

Hematologically important mutations: X-linked chronic granulomatous disease (fourth update)

International audienceChronic granulomatous disease (CGD) is an immunodeficiency disorder affecting about 1 in 250,000 individuals. CGD patients suffer from severe bacterial and fungal infections. The disease is caused by a lack of superoxide production by the leukocyte enzyme NADPH oxidase. Superoxide and subsequently formed other reactive oxygen species (ROS) are instrumental in killing phagocytosed micro-organisms in neutrophils, eosinophils, monocytes and macrophages. The leukocyte NADPH oxidase is composed of five subunits, of which the enzymatic component is gp91phox, also called Nox2. This protein is encoded by the CYBB gene on the X chromosome. Mutations in this gene are found in about 70% of all CGD patients in Europe and in about 20% in countries with a high ratio of parental consanguinity. This article lists all mutations identified in CYBB and should therefore help in genetic counseling of X-CGD patients' families. Moreover, apparently benign polymorphisms in CYBB are also given, which should facilitate the recognition of disease-causing mutations. In addition, we also include some mutations in G6PD, the gene on the X chromosome that encodes glucose-6-phosphate dehydrogenase, because inactivity of this enzyme may lead to shortage of NADPH and thus to insufficient activity of NADPH oxidase. Severe G6PD deficiency can induce CGD-like symptoms

Hematologically important mutations: The autosomal forms of chronic granulomatous disease (third update)

Chronic granulomatous disease (CGD) is an immunodeficiency disorder affecting about 1 in 250,000 individuals. CGD patients suffer from severe, recurrent bacterial and fungal infections. The disease is caused by mutations in the genes encoding the components of the leukocyte NADPH oxidase. This enzyme produces superoxide, which is subsequently metabolized to hydrogen peroxide and other reactive oxygen species (ROS). These products are essential for intracellular killing of pathogens by phagocytic leukocytes (neutrophils, eosinophils, monocytes and macrophages). The leukocyte NADPH oxidase is composed of five subunits, four of which are encoded by autosomal genes. These are CYBA, encoding p22(phox), NCF1, encoding p47(phox), NCF2, encoding p67(phox) and NCF4, encoding p40(phox). This article lists all mutations identified in these genes in CGD patients. In addition, cytochrome b(558) chaperone-1 (CYBC1), recently recognized as an essential chaperone protein for the expression of the X-linked NADPH oxidase component gp91(phox) (also called Nox2), is encoded by the autosomal gene CYBC1. Mutations in this gene also lead to CGD. Finally, RAC2, a small GTPase of the Rho family, is needed for activation of the NADPH oxidase, and mutations in the RAC2 gene therefore also induce CGD-like symptoms. Mutations in these last two genes are also listed in this article

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

Sex differences in oncogenic mutational processes

Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Peer reviewe