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

Impact of fecal sludge and municipal solid waste co-compost on crop growth of Raphanus Sativus L. and Capsicum Anuum L. under stress conditions

Co-composted dewatered faecal sludge (FS) with organic fractions of municipal solid waste (MSW) has a high potential to be used as an agricultural resource in Sri Lanka. In addition to options for cost recovery in waste management, closing the nutrient and carbon cycles between urban and rural areas, substitution of mineral fertilizers, reduced pollution. and the restoration of degraded arable land are possible with important benefits. Up to now little is known about the usage of FS-MSW as fertilizer and it needs to be studied in order to achieve a better understanding and generate application recommendations. The aim of these experiments has been to evaluate the possibility of substituting mineral fertilization. Two field experiments were conducted on sandy loam to assess the effects of MSW compost and FS-MSW co-compost, its pelletized forms, and mineral-enriched FS-MSW on crop growth. As a short-term crop Raphanus sativus “Beeralu rabu” (radish) was studied for 50 days in a randomized complete block design (RCDB). Results show that, under drought conditions, FS-MSW co-compost increased the yield significantly, while MSW and FS-MSW compost enabled the highest survival rate of the plants. Similarly, the second field trial with a long-term crop, Capsicum anuum “CA-8” (capsicum), was planted as RCBD, using the same treatments, for a cultivation period of 120 days. Results display that during a drought followed by water saturated soil conditions co-compost treatments achieved comparable yields and increased the survival rate significantly compared to the control, fertilized with urea, triple super phosphate, and muriate of potash. Cost-benefit analysis (CBA) revealed that pelletizing decreased the monetary benefits if only fertilizer value is considered. It can be concluded that, under drought and water stress, co-compost ensures comparable yields and enables more resistance, but might not be economical viable as a one-crop fertilizer. These findings need to be validated with further trials under different climate regimes and soils

Impact of fecal sludge and municipal solid waste co-compost on crop growth of Raphanus Sativus\textit {Raphanus Sativus} L. and Capsicum Anuum\textit {Capsicum Anuum} L. under stress conditions

Co-composted dewatered faecal sludge (FS) with organic fractions of municipal solid waste (MSW) has a high potential to be used as an agricultural resource in Sri Lanka. In addition to options for cost recovery in waste management, closing the nutrient and carbon cycles between urban and rural areas, substitution of mineral fertilizers, reduced pollution. and the restoration of degraded arable land are possible with important benefits. Up to now little is known about the usage of FS-MSW as fertilizer and it needs to be studied in order to achieve a better understanding and generate application recommendations. The aim of these experiments has been to evaluate the possibility of substituting mineral fertilization. Two field experiments were conducted on sandy loam to assess the effects of MSW compost and FS-MSW co-compost, its pelletized forms, and mineral-enriched FS-MSW on crop growth. As a short-term crop $\textit {Raphanus sativus}$ "Beeralu rabu" (radish) was studied for 50 days in a randomized complete block design (RCDB). Results show that, under drought conditions, FS-MSW co-compost increased the yield significantly, while MSW and FS-MSW compost enabled the highest survival rate of the plants. Similarly, the second field trial with a long-term crop, $\textit {Capsicum anuum}$ "CA-8" (capsicum), was planted as RCBD, using the same treatments, for a cultivation period of 120 days. Results display that during a drought followed by water saturated soil conditions co-compost treatments achieved comparable yields and increased the survival rate significantly compared to the control, fertilized with urea, triple super phosphate, and muriate of potash. Cost-benefit analysis (CBA) revealed that pelletizing decreased the monetary benefits if only fertilizer value is considered. It can be concluded that, under drought and water stress, co-compost ensures comparable yields and enables more resistance, but might not be economical viable as a one-crop fertilizer. These findings need to be validated with further trials under different climate regimes and soil

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

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