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

Supermax prisons in America

Supermax zapori v Ameriki, poznani tudi kot ´special control units´, ´intensive management units´, ´special management units´ ali ´security housing units´, so maksimalno varovani zapori, kjer ni prostora za rehabilitacijo, druženje, terapijo ali edukacijo. Kljub temu da se je praksa ekstremne izolacije in deprivacije, ki se v zaporu uporablja s primarnim namenom zaščite javnosti in zagotavljanja varnosti v zaporu, že leta 1900 izkazala kot neučinkovita, neetična, nehumana in draga, je le-ta v zadnjih desetletjih postala daleč najmočnejše orožje v pomenu kaznovanja in nadzornih ukrepov, ki je dostopen zaporskim upravljalcem. Kaznovalni sistem, v teoriji namenjen le najhujšim zločincem, v praksi izkazuje drugačno sliko. Zaradi prenatrpanosti ostalih zaporov, izgredov in kršitev zaporskih pravil v splošnih zaporih se v ekstremni izolaciji v supermaks zaporih najpogosteje znajdejo mladoletniki, duševno bolni in telesno oziroma fizično omejeni zaporniki. Zaradi narave svoje bolezni in procesa odraščanja se le-ti pogosteje znajdejo v konfliktu, ki mu sledi kazen – samica. S problematiko ekstremne izolacije in deprivacije v supermaks zaporih se v zadnjih desetletjih ukvarjajo predvsem organizacije na področju človekovih pravic. Pri tem so zaznale precej kršitev, zaradi katerih so bili izpeljani tudi sodni postopki. Zahvaljujoč se organizacijam, ki ozaveščajo o problematiki supermaks sistema, so se ponekod zadeve premaknile v pozitivno smer. Kljub navedenemu, se mnogi namreč ne zavedajo dejstva, da problem ekstremne izolacije ne zadeva zgolj zaporski sistem in same zapornike, temveč ima negativen vpliv tudi na javnost. Večina zapornikov prej ali slej svojo kazen odsluži in se tako brez kakršnih koli rehabilitacijskih programov vrne nazaj v skupnost, kar pa pogosto privede do povratništva. Gre namreč za začaran krog, kjer bi bilo učinkoviteje poskrbeti za preventivo kot kurativo.Supermax prisons in America, also known as ´special control units´, ´intensive management units´, ´special management units´ or ´security housing units´, are maxium security prisons where there is no room for rehabilitation, socializing with others, therapy or education. Despite the fact that the practices of extreme isolation and deprivation, used in a high number of prisons whose primary objective is to protect the public from criminals and at the same time to ensure that there will always be a safe and secure environment in prisons, already proved to be a highly ineffective, unethical, inhuman and expensive way back in 1900, but over the past decades it has once again become by far the most powerful weapon, so easily accessible to prison operators as far as punishment and control measures is concerned. Within the criminal justice system, the penalty system – in theory – it is designed for the offenders who commit serious crimes, i. e. the worst criminals, but in practice a totally different picture emerges. Due to overcrowding of all the other general prison facilities, disturbances, riots and violation of the prison rules, minors, mentally and physically ill prisoners often find themselves held in extreme isolation in these supermax prisons. As a result of the very nature of their illness, since suffering from a mental illness or being physically disabled, and if considering the way they usually grow up (minors or teenagers) these young adults often find themselves caught up in the middle of a conflict which is in most cases followed by a punishment - a solitary confinement. There are several human rights organizations that have been trying to deal with this issue, so strongly associated with extreme isolation and sensory deprivation in supermax prisons, over the last few decades due to the fact that there has been a number of violations and a series of irregularities detected not only in this system, but also in the judicial system. These organizations are the ones that have been trying to raise awareness of the problems most supermax prisons face and it is all thanks to them that in certain isntitutions things have been moving into a positive direction. Unfortunately, there are still a lot of people who do not realize or understand that problems dealing with extreme isolation do not represent an issue or affects only the prison system and all the prisoners within, but they also have a negative impact on the public as well. Most prisoners sooner or later finish their prison sentence and then they return into the community without being offered any prison rehabilitation or work programs. As a consequence, the recidivism patterns of former prisoners is quite high. It is indeed a vicious circle as far as the prison system is concerned and when it comes to this issue we should be aware of the fact that prevention is always much better than cure itself

Correlating structural properties with electrochemical behavior of non-graphitizable carbons in Na-ion batteries

We report on a detailed structural versus electrochemical property investigation of the corncob-derived non-graphitizable carbons prepared at different carbonization temperatures using a combination of structural characterization methodology unique to this field. Non-graphitizable carbons are currently the most viable option for the negative electrode in sodium-ion batteries. However, many challenges arise from the strong dependence of the precursor’s choice and carbonization parameters on the evolution of the carbon matrix and its resulting electrochemistry. We followed structure development upon the increase in carbonization temperature with thorough structural characterization and electrochemical testing. With the increase of carbonization temperature from 900 to 1600 °C, our prepared materials exhibited a trend toward increasing structural order, an increase in the specific surface area of micropores, the development of ultramicroporosity, and an increase in conductivity. This was clearly demonstrated by a synergy of small- and wide-angle X-ray scattering, scanning transmission electron microscopy, and electron-energy loss spectroscopy techniques. Three-electrode full cell measurements confirmed incomplete desodiation of Na$^+$ ions from the non-graphitizable carbons in the first cycle due to the formation of a solid−electrolyte interface and Na trapping in the pores, followed by a stable second cycle. The study of cycling stability over 100 cycles in a half-cell configuration confirmed the observed high irreversible capacity in the first cycle, which stabilized to a slow decrease afterward, with the Coulombic efficiency reaching 99% after 30 cycles and then stabilizing between 99.3 and 99.5%. Subsequently, a strong correlation between the determined structural properties and the electrochemical behavior was established

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

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

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 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 (VAFPeer reviewe