21 research outputs found
Book Review - Christian Citizens: Reading the Bible in Black and White in the Postemancipation South
Recommended from our members
The impact of tumor profiling approaches and genomic data strategies for cancer precision medicine
Background: The diversity of clinical tumor profiling approaches (small panels to whole exomes with matched or unmatched germline analysis) may engender uncertainty about their benefits and liabilities, particularly in light of reported germline false positives in tumor-only profiling and use of global mutational and/or neoantigen data. The goal of this study was to determine the impact of genomic analysis strategies on error rates and data interpretation across contexts and ancestries. Methods: We modeled common tumor profiling modalities—large (n = 300 genes), medium (n = 48 genes), and small (n = 15 genes) panels—using clinical whole exomes (WES) from 157 patients with lung or colon adenocarcinoma. We created a tumor-only analysis algorithm to assess germline false positive rates, the impact of patient ancestry on tumor-only results, and neoantigen detection. Results: After optimizing a germline filtering strategy, the germline false positive rate with tumor-only large panel sequencing was 14 % (144/1012 variants). For patients whose tumor-only results underwent molecular pathologist review (n = 91), 50/54 (93 %) false positives were correctly interpreted as uncertain variants. Increased germline false positives were observed in tumor-only sequencing of non-European compared with European ancestry patients (p < 0.001; Fisher’s exact) when basic germline filtering approaches were used; however, the ExAC database (60,706 germline exomes) mitigated this disparity (p = 0.53). Matched and unmatched large panel mutational load correlated with WES mutational load (r2 = 0.99 and 0.93, respectively; p < 0.001). Neoantigen load also correlated (r2 = 0.80; p < 0.001), though WES identified a broader spectrum of neoantigens. Small panels did not predict mutational or neoantigen load. Conclusions: Large tumor-only targeted panels are sufficient for most somatic variant identification and mutational load prediction if paired with expanded germline analysis strategies and molecular pathologist review. Paired germline sequencing reduced overall false positive mutation calls and WES provided the most neoantigens. Without patient-matched germline data, large germline databases are needed to minimize false positive mutation calling and mitigate ethnic disparities. Electronic supplementary material The online version of this article (doi:10.1186/s13073-016-0333-9) contains supplementary material, which is available to authorized users
Pandemic as Opportunity
The COVID-19 pandemic presented the Kennesaw State University Library System with the question, " How can the library maintain live face-to-face reference services in a manner that is safe for all involved ?" Challenges to creating a live virtual reference desk that arose included the need to serve two campuses simultaneously, librarians working from home, and using conferencing technology in unexplored ways. The resulting Virtual In-Person (VIP) Reference service was the answer to our immediate situation, yet lessons were learned for future opportunities to push our services beyond the traditional
Pandemic as Opportunity: Creating and Implementing a Live Virtual Reference Desk
The COVID-19 pandemic presented the Kennesaw State University Library System with the question, How can the library maintain live face-to-face reference services in a manner that is safe for all involved ? Challenges to creating a live virtual reference desk that arose included the need to serve two campuses simultaneously, librarians working from home, and using conferencing technology in unexplored ways. The resulting Virtual In-Person (VIP) Reference service was the answer to our immediate situation, yet lessons were learned for future opportunities to push our services beyond the traditional
Role of the polarity protein, Scribble, in Hematopoiesis and Leukemia
The polarity protein, Scribble, is a member of a group of proteins responsible for the apical basal polarity in epithelia. Scribble is highly conserved from flies to humans and is deregulated in a number of human epithelial cancers including cervical, colon, breast and prostate but its role in blood cancers has not been explored. As Scribble knockout mice are embryonic lethal, dying from a severe neural tube closure defect, we have developed conditional knockout mice using the Mx1-Cre model to explore the role of Scribble in hematopoiesis in both steady state and leukemia. Expression of Scribble in hematopoietic organs and specific lineages was confirmed using multiple approaches. We established that loss of PTEN results in myeloproliferative disease with progression to T-ALL or AML/T-ALL. Pten/Scribble double knockouts have similar symptoms of disease as Pten single knockouts: splenomegaly, hepatomegaly, enlarged lymph nodes and thymus, terminal deoxynucleotidyl transferase (Tdt)-positive cells in the thymus and/or an abundance of blasts in the spleen. Both Pten single knockouts and Pten/Scribble double knockouts have a block in the Pre-Pro B stage of B cell development in the bone marrow and in the DN1 stage of T cell differentiation in the thymus. Preliminary examination of disease burden between Pten single knockouts and Pten/Scribble double knockouts suggests a shift from T-ALL to AML in Pten/Scribble double knockouts. We are currently investigating this and other differences between double and single knockout mice and the underlying mechanisms for these differences with the ultimate aim of generating novel chemotherapeutic targets for treatment of T-ALL and AM