Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors.

Whole-exome sequencing of cell-free DNA (cfDNA) could enable comprehensive profiling of tumors from blood but the genome-wide concordance between cfDNA and tumor biopsies is uncertain. Here we report ichorCNA, software that quantifies tumor content in cfDNA from 0.1× coverage whole-genome sequencing data without prior knowledge of tumor mutations. We apply ichorCNA to 1439 blood samples from 520 patients with metastatic prostate or breast cancers. In the earliest tested sample for each patient, 34% of patients have ≥10% tumor-derived cfDNA, sufficient for standard coverage whole-exome sequencing. Using whole-exome sequencing, we validate the concordance of clonal somatic mutations (88%), copy number alterations (80%), mutational signatures, and neoantigens between cfDNA and matched tumor biopsies from 41 patients with ≥10% cfDNA tumor content. In summary, we provide methods to identify patients eligible for comprehensive cfDNA profiling, revealing its applicability to many patients, and demonstrate high concordance of cfDNA and metastatic tumor whole-exome sequencing.

Energy Contents of Frequently Ordered Restaurant Meals and Comparison with Human Energy Requirements and U.S. Department of Agriculture Database Information: A Multisite Randomized Study.

BACKGROUND: Excess energy intake from meals consumed away from home is implicated as a major contributor to obesity, and ∼50% of US restaurants are individual or small-chain (non-chain) establishments that do not provide nutrition information. OBJECTIVE: To measure the energy content of frequently ordered meals in non-chain restaurants in three US locations, and compare with the energy content of meals from large-chain restaurants, energy requirements, and food database information. DESIGN: A multisite random-sampling protocol was used to measure the energy contents of the most frequently ordered meals from the most popular cuisines in non-chain restaurants, together with equivalent meals from large-chain restaurants. SETTING: Meals were obtained from restaurants in San Francisco, CA; Boston, MA; and Little Rock, AR, between 2011 and 2014. MAIN OUTCOME MEASURES: Meal energy content determined by bomb calorimetry. STATISTICAL ANALYSIS PERFORMED: Regional and cuisine differences were assessed using a mixed model with restaurant nested within region×cuisine as the random factor. Paired t tests were used to evaluate differences between non-chain and chain meals, human energy requirements, and food database values. RESULTS: Meals from non-chain restaurants contained 1,205±465 kcal/meal, amounts that were not significantly different from equivalent meals from large-chain restaurants (+5.1%; P=0.41). There was a significant effect of cuisine on non-chain meal energy, and three of the four most popular cuisines (American, Italian, and Chinese) had the highest mean energy (1,495 kcal/meal). Ninety-two percent of meals exceeded typical energy requirements for a single eating occasion. CONCLUSIONS: Non-chain restaurants lacking nutrition information serve amounts of energy that are typically far in excess of human energy requirements for single eating occasions, and are equivalent to amounts served by the large-chain restaurants that have previously been criticized for providing excess energy. Restaurants in general, rather than specific categories of restaurant, expose patrons to excessive portions that induce overeating through established biological mechanisms.