Characterizing the Genomic Profile in High-Grade Gliomas: From Tumor Core to Peritumoral Brain Zone, Passing through Glioma-Derived Tumorspheres

Glioblastoma is an extremely heterogeneous disease. Treatment failure and tumor recurrence primarily reflect the presence in the tumor core (TC) of the glioma stem cells (GSCs), and secondly the contribution, still to be defined, of the peritumoral brain zone (PBZ). Using the array-CGH platform, we deepened the genomic knowledge about the different components of GBM and we identified new specific biomarkers useful for new therapies. We firstly investigated the genomic profile of 20 TCs of GBM; then, for 14 cases and 7 cases, respectively, we compared these genomic profiles with those of the related GSC cultures and PBZ biopsies. The analysis on 20 TCs confirmed the intertumoral heterogeneity and a high percentage of copy number alterations (CNAs) in GBM canonical pathways. Comparing the genomic profiles of 14 TC-GSC pairs, we evidenced a robust similarity among the two samples of each patient. The shared imbalanced genes are related to the development and progression of cancer and in metabolic pathways, as shown by bioinformatic analysis using DAVID. Finally, the comparison between 7 TC-PBZ pairs leads to identifying PBZ-unique alterations, which it has been identified, require further investigation.

The limits of personalization in precision medicine: Polygenic risk scores and racial categorization in a precision breast cancer screening trial

Population-based genomic screening is at the forefront of a new approach to disease prevention. Yet the lack of diversity in genome wide association studies and ongoing debates about the appropriate use of racial and ethnic categories in genomics raise key questions about the translation of genomic knowledge into clinical practice. This article reports on an ethnographic study of a large pragmatic clinical trial of breast cancer screening called WISDOM (Women Informed to Screen Depending On Measures of Risk). Our ethnography illuminates the challenges of using race or ethnicity as a risk factor in the implementation of precision breast cancer risk assessment. Our analysis provides critical insights into how categories of race, ethnicity and ancestry are being deployed in the production of genomic knowledge and medical practice, and key challenges in the development and implementation of novel Polygenic Risk Scores in the research and clinical applications of this emerging science. Specifically, we show how the conflation of social and biological categories of difference can influence risk prediction for individuals who exist at the boundaries of these categories, affecting the perceptions and practices of scientists, clinicians, and research participants themselves. Our research highlights the potential harms of practicing genomic medicine using under-theorized and ambiguous categories of race, ethnicity, and ancestry, particularly in an adaptive, pragmatic trial where research findings are applied in the clinic as they emerge. We contribute to the expanding literature on categories of difference in post-genomic science by closely examining the implementation of a large breast cancer screening study that aims to personalize breast cancer risk using both common and rare genomic markers.

OmniSARS2: A Highly Sensitive and Specific RT-qPCR-Based COVID-19 Diagnostic Method Designed to Withstand SARS-CoV-2 Lineage Evolution

Extensive transmission of SARS-CoV-2 during the COVID-19 pandemic allowed the generation of thousands of mutations within its genome. While several of these become rare, others largely increase in prevalence, potentially jeopardizing the sensitivity of PCR-based diagnostics. Taking advantage of SARS-CoV-2 genomic knowledge, we designed a one-step probe-based multiplex RT-qPCR (OmniSARS2) to simultaneously detect short fragments of the SARS-CoV-2 genome in ORF1ab, E gene and S gene. Comparative genomics of the most common SARS-CoV-2 lineages, other human betacoronavirus and alphacoronavirus, was the basis for this design, targeting both highly conserved regions across SARS-CoV-2 lineages and variable or absent in other Coronaviridae viruses. The highest analytical sensitivity of this method for SARS-CoV-2 detection was 94.2 copies/mL at 95% detection probability (~1 copy per total reaction volume) for the S gene assay, matching the most sensitive available methods. In vitro specificity tests, performed using reference strains, showed no cross-reactivity with other human coronavirus or common pathogens. The method was compared with commercially available methods and detected the virus in clinical samples encompassing different SARS-CoV-2 lineages, including B.1, B.1.1, B.1.177 or B.1.1.7 and rarer lineages. OmniSARS2 revealed a sensitive and specific viral detection method that is less likely to be affected by lineage evolution oligonucleotide–sample mismatch, of relevance to ensure the accuracy of COVID-19 molecular diagnostic methods.

Mitochondrial Genomes, Phylogenetic Associations, and SNP Recovery for the Key Invasive Ponto-Caspian Amphipods in Europe

The Ponto-Caspian region is the main donor of invasive amphipods to freshwater ecosystems, with at least 13 species successfully established in European inland waters. Dikerogammarus spp. and Pontogammarus robustoides are among the most successful, due to their strong invasive impact on local biota. However, genomic knowledge about these invaders is scarce, while phylogeography and population genetics have been based on short fragments of mitochondrial markers or nuclear microsatellites. In this study, we provide: (i) a reconstruction of six mitogenomes for four invasive gammarids (D. villosus, D. haemobaphes, D. bispinosus, and P. robustoides); (ii) a comparison between the structure of the newly obtained mitogenomes and those from the literature; (iii) SNP calling rates for individual D. villosus and D. haemobaphes from different invasion sites across Europe; and (iv) the first time-calibrated full mitogenome phylogeny reconstruction of several Ponto-Caspian taxa. We found that, in comparison to other gammarids, the mitogenomes of Ponto-Caspian species show a translocation between the tRNA-E and tRNA-R positions. Phylogenetic reconstruction using the mitogenomes identified that Ponto-Caspian gammarids form a well-supported group that originated in the Miocene. Our study supports paraphyly in the family Gammaridae. These provided mitogenomes will serve as vital genetic resources for the development of new markers for PCR-based identification methods and demographic studies.

SARS COV-2: Exploring the Virus of the Century

Coronaviruses comprise a large family of viruses that cause respiratory and intestinal infections in animals and humans. This recent outbreak of unusual respiratory disease plaguing the entire world has been named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the basis of phylogenetic analysis of related coronaviruses. Its transmission occurs mainly through airborn, fomite and other modes. Structurally, it is similar to other coronaviruses and has four major structural proteins; the spike surface glycoprotein (S), small envelope protein (E), matrix protein (M) and nucleocapsid protein (N). The M protein is most abundant and is responsible for intracellular formation of virus particles. S protein induces antibody generation and is involved in intracellular virus entry. Drug combinations are being tried on the basis of structural and genomic knowledge of the virus. Various researchers have found that the SARS CoV2 has many strains among which L type is most pathogenic and D614 type is most infective. All this information has been collected in this review to understand the virus behind this calamity in depth and to make it handy for the researchers to search literature related to SARS COV2. Keywords: SARS COV2, spike glycoprotein, L type strain, D614 strain.

A snapshot of nurses’ understanding, perceptions and comfort level of genomics

Objective: The primary aim of this study explored holistic nurses’ self-perceived genomic knowledge, perceptions, attitude and comfort of genomics. A second aim compared results to previous findings of nurse educators and advanced degree practicing registered nurses’ genomic knowledge utilizing the same survey instruments.Methods: Design: Recruitment of participants, through the American Holistic Nurses Association (AHNA), was achieved via an anonymous Survey Monkey link of the Genetic and Genomic Literacy Assessment (GGLA) survey. The GGLA survey comprised three aspects: Self-Perceived Genomic Knowledge Survey; Perceptions and Attitudes about Genomics Integration into Nursing Practice Survey and the Comfort Level of Genomics Survey. Method: The GGLA survey link was made available via the AHNA newsletter.Results: Holistic nurses (n = 41) self-perceived genomic knowledge level demonstrated a knowledge base gap in their comprehension and ability to explain genomic concepts to their patients. Majority of holistic nurses were significantly not comfortable with their genomic knowledge (90% or greater). Comparison with nurse educators (n = 53) and advanced degree practicing registered nurses’ (n = 36) genomic knowledge provided additional insight.Conclusions: A significant majority of nurses are unprepared to adopt genomics into their practice whilst experiencing a lack comfort and confidence. The global success of nursing practice resides with its’ practitioners being fully informed and competent with all required competencies, especially if nursing is to remain prevalent within personalized healthcare.

Genomic Characterization of the Barnacle Balanus improvisus Reveals Extreme Nucleotide Diversity in Coding Regions

Barnacles are key marine crustaceans in several habitats, and they constitute a common practical problem by causing biofouling on man-made marine constructions and ships. Despite causing considerable ecological and economic impacts, there is a surprising void of basic genomic knowledge, and a barnacle reference genome is lacking. We here set out to characterize the genome of the bay barnacle Balanus improvisus (= Amphibalanus improvisus) based on short-read whole-genome sequencing and experimental genome size estimation. We show both experimentally (DNA staining and flow cytometry) and computationally (k-mer analysis) that B. improvisus has a haploid genome size of ~ 740 Mbp. A pilot genome assembly rendered a total assembly size of ~ 600 Mbp and was highly fragmented with an N50 of only 2.2 kbp. Further assembly-based and assembly-free analyses revealed that the very limited assembly contiguity is due to the B. improvisus genome having an extremely high nucleotide diversity (π) in coding regions (average π ≈ 5% and average π in fourfold degenerate sites ≈ 20%), and an overall high repeat content (at least 40%). We also report on high variation in the α-octopamine receptor OctA (average π = 3.6%), which might increase the risk that barnacle populations evolve resistance toward antifouling agents. The genomic features described here can help in planning for a future high-quality reference genome, which is urgently needed to properly explore and understand proteins of interest in barnacle biology and marine biotechnology and for developing better antifouling strategies.

Crowdfunding Conservation Science: Tracing the Participatory Dynamics of Native Parrot Genome Sequencing

Who gets to practice and participate in science? Research teams in Puerto Rico and New Zealand have each sequenced the genomes of parrot populations native to these locales: the iguaca and kākāpō, respectively. In both cases, crowdfunding and social media were instrumental in garnering public interest and funding. These forms of Internet-mediated participation impacted how conservation science was practiced in these cases and shaped emergent social roles and relations. As citizens “follow,” fund, and “like” the labor of conservation, they create new relational possibilities for and with science. For example, the researchers became newly engaged and engaging by narrating and displaying the parrots via an Internet-inflected aesthetic. The visibility of online modalities shifted accountabilities as researchers considered whom this crowdfunded work answered to and how to communicate their progress and results. The affordances of the Internet allowed researchers from the peripheries of the scientific establishment to produce genomic knowledge for globally dispersed audiences. The convergence of genomic and Internet technology here shaped scientific practice by facilitating new modes of participation—for laypeople in science but also for scientists in society.

Utility and Diversity: Challenges for Genomic Medicine

Genomic information is poised to play an increasing role in clinical care, extending beyond highly penetrant genetic conditions to less penetrant genotypes and common disorders. But with this shift, the question of clinical utility becomes a major challenge. A collaborative effort is necessary to determine the information needed to evaluate different uses of genomic information and then acquire that information. Another challenge must also be addressed if that process is to provide equitable benefits: the lack of diversity of genomic data. Current genomic knowledge comes primarily from populations of European descent, which poses the risk that most of the human population will be shortchanged when health benefits of genomics emerge. These two challenges have defined my career as a geneticist and have taught me that solutions must start with dialogue across disciplinary and social divides. Expected final online publication date for the Annual Review of Genomics and Human Genetics Volume 22 is August 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The Implementation Science for Genomic Health Translation (INSIGHT) Study in Epilepsy: Protocol for a Learning Health Care System

Background Genomic medicine is poised to improve care for common complex diseases such as epilepsy, but additional clinical informatics and implementation science research is needed for it to become a part of the standard of care. Epilepsy is an exemplary complex neurological disorder for which DNA diagnostics have shown to be advantageous for patient care. Objective We designed the Implementation Science for Genomic Health Translation (INSIGHT) study to leverage the fact that both the clinic and testing laboratory control the development and customization of their respective electronic health records and clinical reporting platforms. Through INSIGHT, we can rapidly prototype and benchmark novel approaches to incorporating clinical genomics into patient care. Of particular interest are clinical decision support tools that take advantage of domain knowledge from clinical genomics and can be rapidly adjusted based on feedback from clinicians. Methods Building on previously developed evidence and infrastructure components, our model includes the following: establishment of an intervention-ready genomic knowledge base for patient care, creation of a health informatics platform and linking it to a clinical genomics reporting system, and scaling and evaluation of INSIGHT following established implementation science principles. Results INSIGHT was approved by the Institutional Review Board at the University of Texas Health Science Center at Houston on May 15, 2020, and is designed as a 2-year proof-of-concept study beginning in December 2021. By design, 120 patients from the Texas Comprehensive Epilepsy Program are to be enrolled to test the INSIGHT workflow. Initial results are expected in the first half of 2023. Conclusions INSIGHT’s domain-specific, practical but generalizable approach may help catalyze a pathway to accelerate translation of genomic knowledge into impactful interventions in patient care. International Registered Report Identifier (IRRID) PRR1-10.2196/25576