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

A Central Asian city on the Silk Road: ancient and medieval Merv

In the 11th century AD, Merv was one of the world's largest and most splendid cities. Today it is a h uge archaeological site, the complexities of which are being unravelled by the International Merv Project (IMP). Here the Director of the IMP charts the succession of cities that have flourished in the Merv oasis and describes the work of the project

Monuments of Merv

Archaeological research and ancient records have been combined in this work to provide a comprehensive account of the buildings of Merv, an oasis city in the middle of the Turkmenistani desert. Founded in the sixth century BC, Merv was a key staging post along the Central Asian trade routes linking Europe and India, and its buildings - palaces, pavilions, gardens and towers springing from the sand - impressed all who visited it. Although eroded by time and weather, enough remains of these buildings to illustrate the evolution of architectural styles in the early medieval and Seljuk eras (7th to 13th cents AD), a period during which the Islamic world developed its own unique range of building types and decorative motifs. This book examines in detail each of the surviving buildings of Merv, discussing their form and function – from palaces to ice-houses, from fortified watch-towers to libraries and dovecotes. Details of doors, windows, corridors and stairways, monumental entrances, rooms, domes and vaults, niches, wall decoration and flooring are described and illustrated in great detail. The book will serve as a major resource for scholars of Islamic architecture

Assyrian Nimrud and the Phoenicians

The first ivories at the Assyrian imperial capital of Kalhu/Nimrud in northern Iraq were found by Henry Layard in the mid-19th century. Max Mallowan and David Oates (both professors at the Institute of Archaeology), together with the British School of Archaeology in Iraq, worked there from 1949–1963 and found literally thousands more, both in the palaces of the acropolis and in a large outlying building known as Fort Shalmaneser. During the last 50 years the majority has been published in the Ivories from Nimrud series, so that it is now possible to look at this remarkable corpus as a whole. It immediately becomes evident that most were not made in Assyria, but imported from the states conquered by the Assyrian kings in the early 1st millennium BC. Many show a debt to the art of Egypt and can be assigned to the ‘Phoenician tradition’, thus recording the otherwise little-known art of the Phoenicians, long famed as master craftsmen. ‘Syrian-Intermediate’ ivories are versions of Phoenician ivories and may represent the art of the recently-arrived Aramaean kingdoms, while the very different ‘North Syrian’ ivories derive from earlier Hittite traditions

A multi-layered approach to developing academic written communication skills for nursing students

Objectives: Academic literacy in nursing students has historically been poor this research therefore aimed to investigate the effectiveness of an embedded multidisciplinary approach to academic written communication skills for first year Bachelor of Nursing students in Australia. Methods: This initiative consisted of (1) collaboratively embedding academic skills with nursing staff and Learning and Academic Skills Advisors using scaffolded tasks, curriculum/material development, workshops/tutorials on writing skills; and (2) individual support sessions. Data was obtained via questionnaire. Results: Responses were received from 92 (74% local and 26% international) students. Key findings showed the collaborative approach to embedding skills with added follow up, was beneficial for students' skills development, including improved academic writing, increased confidence, and recognition of the importance of academic writing. Conclusions: It is important to equip student to develop academic literacy and an embedded academic literacy program has been determined to assist and may contribute to future professionalisation in nursing. © 2023 Walter de Gruyter GmbH, Berlin/Boston

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

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

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