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

Robust Optimal Control of a Microbial Batch Culture Process

This paper considers the microbial batch culture process for producing 1,3-propanediol (1,3-PD) via glycerol fermentation. Our goal was to design an optimal control scheme for this process, with the aim of balancing two (perhaps competing) objectives: (i) the process should yield a sufficiently high concentration of 1,3-PD at the terminal time and (ii) the process should be robust with respect to changes in various uncertain system parameters. Accordingly, we pose an optimal control problem, in which both process yield and process sensitivity are considered in the objective function. The control variables in this problem are the terminal time of the batch culture process and the initial concentrations of biomass and glycerol in the batch reactor. By performing a time-scaling transformation and introducing an auxiliary dynamic system to calculate process sensitivity, we obtain an equivalent optimal control problem in standard form. We then develop a particle swarm optimization algorithm for solving this equivalent problem. Finally, we explore the trade-off between process efficiency and process robustness via numerical simulations

Influence of additive system (Al2O3-RE2O3 , RE = Y, La, Nd, Dy, Yb) on microstructure and mechanical properties of silicon nitride-based ceramics

Silicon nitride based ceramics have been widely used as structural ceramics, due mainly to their thermo-mechanical properties such as high density, high thermal shock resistance, corrosion resistance and chemical stability. The aim of this study was to determine the influence of rare earth and aluminum oxide additions as sintering aids on densification, microstructure and mechanical properties of silicon nitride. Silicon nitride mixtures with 91 wt. (%) Si3N4 and 9% wt. (%) additives were prepared and sintered. The density, microstructure and mechanical properties of the sintered specimens of these mixtures were determined. In most specimens, scanning electron microscopic examination and X ray diffraction analysis revealed elongated grains of &#946;-Si3N4 with aspect ratio of about 2.0 and dispersed in a glassy phase. The density of the sintered specimens was higher than 94% of the theoretical density (td) and specimens with La2O3 and Al2O3 additions exhibited the highest value. The results of this investigation indicate that the rare earth ion size influences densification of silicon nitride, but this correlation was not observed in specimens containing two different rare earth oxides. The hardness values varied in direct proportion to the density of the specimens and the fracture toughness values were influenced by the composition of the intergranular glassy phase

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