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

Geology of Elu Inlet and Melville Sound, Nunavut, Arctic Canada

We present the results of helicopter- and field-based geological mapping of Elu Inlet and Melville Sound, Kitikmeot Region of Nunavut, Arctic Canada. The area includes a ∼150 km-wide belt of Proterozoic sedimentary rocks that unconformably overlie the Archean Slave Province of the Canadian Shield and are cross-cut by Neoproterozoic mafic rocks and covered by early Palaeozoic deposits. This work introduces an updated sedimentologic, stratigraphic, and structural framework for the area and is corroborated by geophysical analysis of natural radioactivity. Three Proterozoic sedimentary sequences have been identified, spanning in age from ∼1.9 to ∼1.2 Ga, and including fluvial–aeolian sandstone and shallow-marine carbonate rocks. Mass-spectrometric analyses identified above-baseline concentrations of uranium along the unconformities underlying the two oldest Proterozoic sequences. Proterozoic deposits display weak deformation, related to syn-orogenic foreland and intracratonic-sag stages of the Kilohigok and Elu basins, respectively

Geology of Elu Inlet and Melville Sound, Nunavut, Arctic Canada

<p>We present the results of helicopter- and field-based geological mapping of Elu Inlet and Melville Sound, Kitikmeot Region of Nunavut, Arctic Canada. The area includes a ∼150 km-wide belt of Proterozoic sedimentary rocks that unconformably overlie the Archean Slave Province of the Canadian Shield and are cross-cut by Neoproterozoic mafic rocks and covered by early Palaeozoic deposits. This work introduces an updated sedimentologic, stratigraphic, and structural framework for the area and is corroborated by geophysical analysis of natural radioactivity. Three Proterozoic sedimentary sequences have been identified, spanning in age from ∼1.9 to ∼1.2 Ga, and including fluvial–aeolian sandstone and shallow-marine carbonate rocks. Mass-spectrometric analyses identified above-baseline concentrations of uranium along the unconformities underlying the two oldest Proterozoic sequences. Proterozoic deposits display weak deformation, related to syn-orogenic foreland and intracratonic-sag stages of the Kilohigok and Elu basins, respectively.</p

Exploiting Thermochronology to Quantify Exhumation Histories and Patterns of Uplift Along the Margins of Tibet

The utilization of thermal-chronological data to constrain mountain building processes exploits the links among rock uplift, exhumation, and cooling during orogenesis. Conceptually, periods of rapid uplift and associated denudation will lead to cooling of rocks as they approach Earth’s surface. The linkage between uplift and exhumation can be complex, but in practice exhumation is often assumed to directly track uplift. The reconstruction of temperature-time histories via thermochronologic systems provides a proxy method to relate the cooling of rock as it is exhumed toward the surface to orogenesis. For the rapid exhumation rates that can occur in active orogenic systems the thermal history will be complex as a result of heat advection, rates of propagation of thermal perturbations, and other processes that affect the cooling behavior. These effects become amplified as exhumation rates increase, and in regions experiencing exhumation rates greater than ∼0.2–0.3 mm/yr (0.2–0.3 km/Ma) simple assumptions of cooling through a constant geotherm will bias the subsequent interpretation. Here we explore, through a suite of generalized models, the impact of exhumation rate and duration on the resulting thermal history and apparent age results. We then apply lessons from these simple exhumation systems to data sets from the high-relief ranges along the eastern margin of the Tibetan Plateau to determine exhumation histories constrained by those data. The resulting exhumation histories provide constraints on the onset of Cenozoic exhumation, the subsequent pace of exhumation, and on the tectonic history of one of the major fault systems in the central Longmen Shan

On a Unified Core Characterization Methodology to Support the Systematic Assessment of Rare Earth Elements and Critical Minerals Bearing Unconventional Carbon Ores and Sedimentary Strata

A significant gap exists in our understanding and ability to predict the spatial occurrence and extent of rare earth elements (REE) and certain critical minerals (CM) in sedimentary strata. This is largely due to a lack of existing, systematic, and well-distributed REE and CM samples and analyses in United States sedimentary basins. In addition, the type of sampling and characterization performed to date has generally lacked the resolution and approach required to constrain geologic and geographic heterogeneities typical of subsurface, mineral resources. Here, we describe a robust and systematic method for collecting core scale characterization data that can be applied to studies on the contextual and spatial attributes, the geologic history, and lithostratigraphy of sedimentary basins. The methods were developed using drilled cores from coal bearing sedimentary strata in the Powder River Basin, Wyoming (PRB). The goal of this effort is to create a unified core characterization methodology to guide systematic collection of key data to achieve a foundation of spatially and geologically constrained REEs and CMs. This guidance covers a range of measurement types and methods that are each useful either individually or in combination to support characterization and delineation of REE and CM occurrences. The methods herein, whether used in part or in full, establish a framework to guide consistent acquisition of geological, geochemical, and geospatial datasets that are key to assessing and validating REE and CM occurrences from geologic sources to support future exploration, assessment, and techno-economic related models and analyses

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

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

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

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