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

必要之善与恶 ：黄怡《林叶的四季》中的生态恐惧症、生物关爱与和谐共生 = Necessary good and evil : ecophobia, biophilia and harmonious coexistence in The Four Seasons of Lam Yip by Wong Yi

香港九十后作家黄怡的小说作品《林叶的四季》以十岁小孩林叶为主角，他患有洁癖，但对自然动植物具有丰富的好奇心与怜悯。这部小说集以富有童真的视角展现了他的日常生活景象，其中更有不少故事片段取材自现实新闻，全书结合对人和生态环境与自然万物的关系展开细致的刻画，引人省思。 林叶因洁癖而厌恶沙石泥土、动物粪便等自然事物，但这却又无碍他对遭受压迫或身陷危机的动植物产生关爱之情，甚至伸出援手。因此，本文以生态学理论中的“生态恐惧症”（ecophobia）与“生物关爱”（biophilia）分析解读他的矛盾心理。面对这两种互相对立，却往往同时并存的心理状态，学者Scott Slovic认为这是现代常有的现象，而本文也以中西方的生态哲学思想，例如道德共同体的讨论与儒家思想中强调的“和谐共生”，研究人类面对自然应如何拿捏善恶的尺度与界线。 The Four Seasons of Lam Yip, written by a Hong Kong writer Wong Yi(1991-), describes the daily life stories of a 10-year-old boy Lam Yip, who has a strong curiosity and compassion for natural plants and animals though he suffers from mysophobia. Many of these stories are based on news from the reality, which is thought-provoking and makes space for readers to reflect, specifically about the relationship between human and the natural environment. Lam Yip is caring and sympathetic towards the plants and animals that are in danger and he even lend a helping hand to them, though there are many natural things that he hates such as sand, soil and animal feces. Such ambivalence is discussed with the ecological theories of “ecophobia” and “biophilia”. Then, this paper will study the boundaries of necessary good and evil of human towards the natural environment with both Western and Chinese ecological thoughts and philosophy such as the discussions about moral community, and “harmonious coexistence” （和谐共生）in Confucianism.Bachelor of Arts in Chines

A 64×64 1200fps CMOS ion-image sensor with suppressed fixed-pattern-noise for accurate high-throughput DNA sequencing

A 64×64 CMOS ion-image sensor is demonstrated towards accurate high-throughput DNA sequencing. Dual-mode (pH/image) sensing is performed with ion-sensitive field-effect transistor (ISFET) fabricated in standard CMOS image sensor (CIS) process. After addressing physical locations of DNA slices by optical contact imaging, local pH for one DNA slice can be mapped to its physical address with accurate correlation. Moreover, pixel-to-pixel ISFET threshold voltage mismatch is reduced by correlated double sampling (CDS) readout. Measurements show a sensitivity of 103.8mV/pH and fixed-pattern-noise (FPN) reduction from 4% to 0.3% with speed of 1200fps. .Accepted versio

Sex Steroids Induce Membrane Stress Responses and Virulence Properties in Pseudomonas aeruginosa (vol 11, e01774-20, 2020)

MBIO11

Sex Steroids Induce Membrane Stress Responses and Virulence Properties in Pseudomonas aeruginosa

10.1128/mBio.01774-20MBIO11

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

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