Postsecondary science education has been shaped by Eurocentric ideologies that center science as a set of culturally neutral, color-blind, and meritocratic systems designed to exclude underrepresented groups from positions of power and knowledge production.Nationally, white faculty still predominate senior faculty positions, resulting in few opportunities for students of color to take courses from faculty who share their racial or cultural backgrounds (Haynes & Patton, 2019).At the same time, there is a need to diversify the predominantly female and white elementary teacher workforce as the K12 student population is rapidly diversifying (Januszyk, et al, 2016; NCES 2103).This paper will describe white STEM faculty learning around race, culture, and STEM teaching/learning in a design-based research project in which we are designing science and engineering modules for preservice elementary teachers that deeply integrate scientific concepts and practices, racial equity, and examinations of the history of racist research practices within science itself.
Abstract This study evaluated the status of native and stocked fish species in 13 prairie lakes in central Canada over eight years (2007–14) using three metrics: resource‐use (benthic versus pelagic carbon via stable isotopes); body condition (relative weight index W r ); and parasite load (cestode gut enumerations). Analyses included game and non‐game fishes, like naturally occurring northern pike, Esox lucius L., and yellow perch, Perca flavescens Mitchill, but focused on stocked walleye, Sander vitreus (Mitchill) because it supports a robust recreational fishery. Walleye and northern pike were significantly more reliant on benthic carbon than yellow perch or forage fishes ( p < 0.05), but this reliance was not associated with any measured environmental variables for any species. In lakes with game fishes, forage fishes exhibited higher reliance on benthic energy, possibly due to predator avoidance strategy, particularly yellow perch. Walleye body condition index was consistently lower (<95–105) than values exhibited by the other two game fishes (81–139), and parasites were only common in walleye and associated with lake‐water salinity ( r 2 = 0.93, p < 0.05) and sex ( p < 0.05). Based on the results, the most desirable game fish, walleye, appears less resilient to environmental variability than northern pike and yellow perch, making this species more susceptible to impacts of future climate change.
PURPOSE Homologous recombination deficiency (HRD) assays measure DNA damage repair dysfunction to identify patients with high-grade serous ovarian cancer (HGSOC) who may benefit from poly ADP-ribose polymerase inhibitors (PARPis). Numerous assays are available, but only two have undergone prospective clinical validation. Assay variability can affect patient and provider treatment choices; however, the level of assay variability across laboratory developed tests is unknown. METHODS Friends of Cancer Research initiated a research partnership, inviting HRD assay developers to participate in two blinded analyses. In the first, 11 assay developers reported HRD status for the Cancer Genome Atlas HGSOC data set (In Silico; n = 348) and then 17 assay developers reported HRD status for nucleic acids freshly extracted from archival specimens (n = 90) from patients with advanced HGSOC (clinical). HRD status was compared for each analysis. RESULTS The median (IQR) pairwise positive percent agreement (PPA) for the in silico analysis was 74% (51%-89%) and 81% (64%-92%) for pairwise negative percent agreement (NPA); for the clinical analysis PPA was 83% (70%-91%) and NPA was 80% (62%-91%). There was higher positive agreement on HRD status calls among those with a BRCA1 or BRCA2 mutation and a higher negative agreement in CCNE1 -amplified cases. Sample characteristics like tissue block age were not observed to be associated with agreement. A subgroup of tumors largely called HRD across assays with no BRCA1 or BRCA2 mutations was associated with better outcomes on standard platinum-based therapy compared with not HRD; however, the subgroup was small, and further research is warranted. CONCLUSION This analysis demonstrates how results from 20 HRD assays compare when assessing HGSOC. The results set the stage to improve alignment and establish standards for acceptable levels of agreement moving forward.
1582 Background: ctDNA is a potentially superior means of classifying tumor genotype but predictors of Con with atDNA are not well established. We conducted a prospective multicenter study to determine the feasibility of atDNA genotyping on a Next-Generation Sequencing (NSG) platform and ctDNA genotyping among patients with advanced solid malignancies. ctDNA genotyping was concurrently performed and variables associated with Con were investigated. Methods: Patients at 5 BC Cancer Agency Centers were enrolled over 14 months. atDNA genotype was performed using NSG and high-throughput multiplex amplification of a 27 gene panel (Raindance). ctDNA genotyping was done with Boreal Genomics OnTarget on 4cc plasma from blood collected in Streck tubes processed within 96 hours. Con was determined in “clinical gene” subsets for Colorectal (CR) (KRAS, NRAS, BRAF), Lung (L) (EGFR, KRAS) and Melanoma (M)(BRAF). Results: Of 300 patients, tumor origin was CR (46%), L (28%), M (M) (7.7%), and Other (18%). The number of metastatic sites was 1 in 39% and >1 in 54% and 64% had resected primary tumors. 50% of patients had received systemic or radiation therapy within 3 months (median 18 d of ctDNA) and 48% had ≥1 elevated tumor marker. In multivariate analysis, higher Con was seen in CR compared to L (OR 2.5; 95%CI 1.2, 5.2) and when time between atDNA and ctDNA was ≤1 year versus >1 year (OR 2.4; 95%CI 1.03, 5.5). Con was not affected by # or type of metastasis, receipt of prior therapy, resection of the primary tumor or elevated tumour marker. ctDNA analysis was completed on the initial 181 cases. Conclusions: Concordance between atDNA and ctDNA was lower in L cancer and higher concordance was associated with shorter time interval between surgical and liquid biopsy. It was not associated with extent of metastatic disease and other measured variables. Discordance was more frequently related to variants not found in ctDNA. Updated results for the full cohort will be presented. Clinical trial information: NCT02171286. Colorectal Lung Melanoma p-value KRAS NRAS BRAF EGFR KRAS BRAF Concordance 77% 94% 91% 74% 75% 79% + atDNA - ctDNA 17% 0% 5% 24% 14% 21% - atDNA +ctDNA 6% 6% 4% 2% 11% 0% Overall Concordance 59/83 (71%) 30/57 (53%) 11/14 (79%) 0.043
The rapidly growing biomedical literature has been a challenging target for natural language processing algorithms.One of the tasks these algorithms focus on is called named entity recognition (NER), often employed to tag gene mentions.Here we describe a new approach for this task, an approach that uses graphbased semi-supervised learning to train a Conditional Random Field (CRF) model.Benchmarking it on the BioCreative II Gene Mention tagging task, we achieved statistically significant improvements in Fmeasure over BANNER, a widely used biomedical NER system.We note that our tool is transductive and modular in nature, and can be integrated with other CRF-based supervised NER tools.
ABSTRACT Nearly 14% of disease-causing germline variants result from disruption of mRNA splicing. Most (67%) DNA variants predicted in silico to disrupt splicing end up classified as variants of uncertain significance (VUS). We developed and validated an analytic workflow — Sp lice E ffect E vent R esolver (SPEER) — that uses mRNA sequencing to reveal significant deviations in splicing, pinpoints the DNA variants potentially responsible, and measures the deleterious effect of the altered splicing on mRNA transcripts, providing evidence to assess the pathogenicity of the variant. SPEER was used to analyze leukocyte RNA encoding 63 hereditary cancer syndrome genes in 20,317 individuals undergoing clinical genetic testing. Among 3,563 (17.5%) individuals with at least one DNA variant predicted to affect splicing, 971 (4.8%) had altered splicing with a deleterious effect on the transcript and 31 had altered splicing due to a DNA variant located outside our laboratory’s reportable range. Integrating SPEER results into variant interpretation allowed reclassification of VUS to P/LP in 0.4% and to B/LB in 5.9% of the 20,317 patients. SPEER evidence had a significantly higher impact on allowing P/LP and B/LB interpretations in non-White individuals than in non-Hispanic White individuals, illustrating that evidence derived from RNA splicing analysis may reduce ethnic/ancestral disparities in genetic testing.
Abstract Objectives Non-invasive prenatal testing requires the presence of fetal DNA in maternal plasma. Understanding how preexamination conditions affect the integrity of cell-free DNA (cfDNA) and fetal fraction (FF) are a prerequisite for test implementation. Therefore, we examined the adjusted effect that EDTA and Streck tubes have on the cfDNA quantity and FF. Methods A total of 3,568 maternal blood samples across Canada were collected in either EDTA, or Streck tubes, and processing metrics, maternal body mass index (BMI), gestational age and fetal karyotype and sex were recorded. Plasma samples were sequenced using two different sequencing platforms in separate laboratories. Sequencing data were processed with SeqFF to estimate FF. Linear regression and multivariate imputation by chained equations were used to estimate the adjusted effect of tube type on cfDNA and FF. Results We found a positive association between cfDNA quantity and blood shipment time in EDTA tubes, which is significantly reduced with the use of Streck tubes. Furthermore, we show the storage of plasma at −80 °C is associated with a 4.4% annual relative decrease in cfDNA levels. FF was not associated with collection tube type when controlling for confounding variables. However, FF was positively associated with gestational age and trisomy 21, while negatively associated with BMI, male fetus, trisomy 18, Turners syndrome and triploidy. Conclusions Preexamination, maternal and fetal variables are associated with cfDNA quantity and FF. The consideration of these variables in future studies may help to reduce the number of pregnant women with inconclusive tests as a result of low FF.
