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  • br B Spectra of mutations identified genome wide

    2022-09-01


    (B) Spectra of mutations identified genome-wide in two exemplar stock cell lines (top panels) and in their corresponding single cells (bottom panels), genome-wide or within haploid regions at the indicated variant allele fractions (VAF). Each panel is displayed according to the 96-substitution classification on the hor-
    izontal axis defined by the six color-coded substitution types and sequence context immediately 50 and 30 to the mutated base. Order of the sequence context follows the standard alphabetical representation (see Figure 6B). Total number of base substitutions is indicated on the top of each panel. C>T variants at NCG contexts and T>C mutations at ATN contexts in stock cell lines largely represent germline variation due to the non-availability for most cancer cell lines of normal DNAs from the same individuals.
    (legend on next page)
    Figure S7. Variant Allele Fraction Distribution Plots for Cell Line Clones, Related to Figures 3–5
    (A and B) Distribution plots showing frequencies of the variant Dorsomorphin fractions (VAFs) of mutations that remain after the filtering steps (STAR Methods) in indicated clones analyzed by whole-exome (panel A) or whole-genome sequencing (panel B). VAF peaks often deviate from 50%, expected for clonal heterozygous somatic mutations in a diploid genome, because cancer cell lines are often polyploid and heterozygous copy number changes across the genome can further modulate the distribution of the VAF. Bimodal distributions and subclonal peaks can arise from mixed effects of mutations being acquired on different copy number states of the genome and/or subclonally. Minor proportion of mutations presenting at 100% of the reads in some clones can reflect loss of heterozygosity at the loci of the newly acquired mutations or residual germline variants, mainly in parent clones that were compared against the unmatched normal human genome (STAR Methods). International Journal of Radiation Oncology biology physics
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    Physics Contribution
    Characterizing Spatial Lung Function for Esophageal Cancer Patients Undergoing Radiation Therapy
    Albert Pinder-Arabpour, PhD,* Bernard Jones, PhD,* Richard Castillo, PhD,y Edward Castillo, PhD,z Thomas Guerrero, MD,z Karyn Goodman, MD,* Tracey Schefter, MD,* Jennifer Kwak, MD,* Moyed Miften, PhD,* and Yevgeniy Vinogradskiy, PhD*
    *Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado; yDepartment of Radiation Oncology, Emory University, Winship Cancer Institute, Atlanta, Georgia; and zDepartment of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan
    Summary
    Four-dimensional computed tomography (4DCT)even-tilation has been studied in the lung cancer population but has yet to be extended to patients with esophageal cancer. The purpose of this study was to characterize 4DCT-ventilationebased spatial lung function for pa-tients with esophageal can-cer. The study used radiologist observations and developed quantitative met-rics to assess pretreatment spatial lung function profiles for patients with esophageal cancer. The study presents data that can be used for 
    Purpose: Patients with esophageal cancer treated with chemoradiation and surgery can develop pulmonary complications. Four-dimensional computed tomography eventilation (4DCT-ventilation) is a developing imaging modality that uses 4DCT data to calculate lung ventilation. 4DCT-ventilation has been studied in the lung-cancer population but has yet to be extended to patients with esophageal cancer. The purpose of this study was to characterize 4DCT-ventilationebased spatial lung function for patients with esophageal cancer.
    Methods and Materials: Thirty-five patients with esophageal cancer who underwent 4DCT scans participated in the study. A 4DCT-ventilation map was calculated using the patient’s 4DCT imaging and a density changeebased algorithm. To assess each pa-tient’s ventilation profile, radiologist interpretations and quantitative metrics were used. A radiologist interpreted the 4DCT-ventilation images for lobar-based defects and gravity-dependent atelectasis. The 4DCT-ventilation maps were reduced to single metrics intended to reflect the degree of ventilation heterogeneity. The quantitative metrics included the coefficient of variation and metrics based on the ventilation in each lung and each lung third (superior-inferior ventilation [Vent-SI] and anteroposter-ior ventilation). The functional profile of patients with esophageal cancer was charac-terized and compared (using the Mann-Whitney test) for cohorts based on thoracic comorbidities and radiologist-identified defects.