Single-cell RNA-seq reveals transcriptomic heterogeneity mediated by host-pathogen dynamics in lymphoblastoid cell lines

Lymphoblastoid cell lines (LCLs) are generated by transforming primary B cells with Epstein-Barr virus (EBV) and are used extensively as model systems in viral oncology, immunology, and human genetics research. In this study, we characterized single-cell transcriptomic profiles of five LCLs and present a simple discrete-time simulation to explore the influence of stochasticity on LCL clonal evolution. Single-cell RNA sequencing (scRNA-seq) revealed substantial phenotypic heterogeneity within and across LCLs with respect to immunoglobulin isotype; virus-modulated host pathways involved in survival, activation, and differentiation; viral replication state; and oxidative stress. This heterogeneity is likely attributable to intrinsic variance in primary B cells and host-pathogen dynamics. Stochastic simulations demonstrate that initial primary cell heterogeneity, random sampling, time in culture, and even mild differences in phenotype-specific fitness can contribute substantially to dynamic diversity in populations of nominally clonal cells

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Additional file 1 of Study protocol: maintaining preventive care during public health emergencies through effective coordination

Additional file 1: Supplemental File 1. Data Collection Materials

OVOL2 sustains postnatal thymic epithelial cell identity

Abstract Distinct pathways and molecules may support embryonic versus postnatal thymic epithelial cell (TEC) development and maintenance. Here, we identify a mechanism by which TEC numbers and function are maintained postnatally. A viable missense allele (C120Y) of Ovol2, expressed ubiquitously or specifically in TECs, results in lymphopenia, in which T cell development is compromised by loss of medullary TECs and dysfunction of cortical TECs. We show that the epithelial identity of TECs is aberrantly subverted towards a mesenchymal state in OVOL2-deficient mice. We demonstrate that OVOL2 inhibits the epigenetic regulatory BRAF-HDAC complex, specifically disrupting RCOR1-LSD1 interaction. This causes inhibition of LSD1-mediated H3K4me2 demethylation, resulting in chromatin accessibility and transcriptional activation of epithelial genes. Thus, OVOL2 controls the epigenetic landscape of TECs to enforce TEC identity. The identification of a non-redundant postnatal mechanism for TEC maintenance offers an entry point to understanding thymic involution, which normally begins in early adulthood

Side-effects of COVID-19 on patient care: An INR story

BackgroundNumerous studies have documented reduced access to patient care due to the COVID-19 pandemic, including access to diagnostic or screening tests, prescription medications, and treatment for an ongoing condition. In the context of clinical management for venous thromboembolism, this could result in suboptimal therapy with warfarin. We aimed to determine the impact of the pandemic on utilization of International Normalized Ratio (INR) testing and the percentage of high and low results.MethodsINR data from 11 institutions were extracted to compare testing volume and the percentage of INR results ≥3.5 and ≤1.5 between a pre-pandemic period (January-June 2019, period 1) and a portion of the COVID-19 pandemic period (January-June 2020, period 2). The analysis was performed for inpatient and outpatient cohorts.ResultsTesting volumes showed relatively little change in January and February, followed by a significant decrease in March, April, and May, and then returned to baseline in June. Outpatient testing showed a larger percentage decrease in testing volume compared to inpatient testing. At 10 of the 11 study sites, we observed an increase in the percentage of abnormal high INR results as test volumes decreased, primarily among outpatients.ConclusionThe COVID-19 pandemic impacted INR testing among outpatients which may be attributable to several factors. Increased supratherapeutic INR results during the pandemic period when there was reduced laboratory utilization and access to care is concerning because of the risk of adverse bleeding events in this group of patients. This could be mitigated in the future by offering drive-through testing and/or widespread implementation of home INR monitoring

The effect of the Covid-19 shutdown on glycemic testing and control

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused a halt to in-person ambulatory care. We evaluated how the reduction in access to care affected HbA1c testing and patient HbA1c levels. METHODS: HbA1c data from 11 institutions were extracted to compare testing volume and the percentage of abnormal results between a pre-pandemic period (January-June 2019, period 1) and a portion of the COVID-19 pandemic period (Jan-June 2020, period 2). HbA1c results greater than 6.4% were categorized as abnormal. RESULTS: HbA1C testing volumes decreased in March, April and May by 23, 61 and 40% relative to the corresponding months in 2019. The percentage of abnormal results increased in April, May and June (25, 23, 9%). On average, we found that the frequency of abnormal results increased by 0.31% for every 1% decrease in testing volume (p \u3c 0.0005). CONCLUSION: HbA1c testing volume for outpatients decreased by up to 70% during the early months of the pandemic. The decrease in testing was associated with an increase in abnormal HbA1c results