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

The Nelson Site: A Cody Occupation in Northeastern Colorado

The Nelson site in northeastern Colorado represents a Cody age occupation of the High Plains. Because Paleoindian sites of any age are sparse in the archaeological record, each known occurrence adds significant information about prehistory. The Nelson site has received no formal field investigation; however, a small quantity of data has accumulated over nearly one half century of collecting. The cultural affiliation can be demonstrated with the recovered chipped stone assemblage and a new radiocarbon date, while zooarchaeological assessment of the fauna yields preliminary information about the nature of the occupation and Paleoindian lifeways

Advocate-BREAST: advocates and patients’ advice to enhance breast cancer care delivery, patient experience and patient centered research by 2025

Abstract Purpose The aims of the Advocate-BREAST project are to study and improve the breast cancer (BC) patient experience through education and patient-centered research. Methods In December 2021, an electronic REDCap survey was circulated to 6,918 BC survivors (stage 0–4) enrolled in the Mayo Clinic Breast Disease Registry. The questionnaire asked about satisfaction with BC care delivery, and education and support receive(d) regarding BC linked concerns. Patients also ranked Quality Improvement (QI) proposals. Results The survey received 2,437 responses. 18% had Ductal Carcinoma in Situ, 81% had early breast cancer (EBC), i.e. stage 1–3, and 2% had metastatic breast cancer (MBC). Mean age was 64 (SD 11.8), and mean time since diagnosis was 93 months (SD 70.2). 69.3% of patients received all care at Mayo Clinic. The overall experience of care was good (> 90%). The main severe symptoms recalled in year 1 were alopecia, eyebrow/eyelash thinning, hot flashes, sexual dysfunction, and cognitive issues. The main concerns recalled were fear of BC recurrence/spread; loved ones coping; fear of dying, and emotional health. Patients were most dissatisfied with information regarding sexual dysfunction, eyebrow/eyelash thinning, peripheral neuropathy, and on side effects of immunotherapy/targeted therapies. Top ranking QI projects were: i) Lifetime access to concise educational resources; ii) Holistic support programs for MBC and iii) Wellness Programs for EBC and MBC. Conclusions Patients with early and advanced BC desire psychological support, concise educational resources, and holistic care. Implications Focused research and QI initiatives in these areas will improve the BC patient experience

Late date of human arrival to North America: Continental scale differences in stratigraphic integrity of pre-13,000 BP archaeological sites

By 13,000 BP human populations were present across North America, but the exact date of arrival to the continent, especially areas south of the continental ice sheets, remains unclear. Here we examine patterns in the stratigraphic integrity of early North American sites to gain insight into the timing of first colonization. We begin by modeling stratigraphic mixing of multicomponent archaeological sites to identify signatures of stratigraphic integrity in vertical artifact distributions. From those simulations, we develop a statistic we call the Apparent Stratigraphic Integrity Index (ASI), which we apply to pre- and post-13,000 BP archaeological sites north and south of the continental ice sheets. We find that multiple early Beringian sites dating between 13,000 and 14,200 BP show excellent stratigraphic integrity. Clear signs of discrete and minimally disturbed archaeological components do not appear south of the ice sheets until the Clovis period. These results provide support for a relatively late date of human arrival to the Americas