SARS-CoV-2 SPIKE Antibody Levels can Indicate Immuno-Resilience to Re-infection: a Real-World Study.

Introduction: The use of antibody titers against SARS-CoV-2, as a method of estimating subsequent infection following infection or vaccination, is unclear. Here, we investigate whether specific levels of antibodies, as markers of adaptive immunity, can serve to estimate the risk of symptomatic SARS-CoV-2 (re-) infection.

Methods: In this real-world study, laboratory data from individuals tested for SARS-CoV-2 antibodies under routine clinical conditions were linked through tokenization to a United States medical insurance claims database to determine the risk of symptomatic/severe SARS-CoV-2 infection outcomes.

A program for real-time surveillance of SARS-CoV-2 genetics.

The COVID-19 pandemic brought forth an urgent need for widespread genomic surveillance for rapid detection and monitoring of emerging SARS-CoV-2 variants. It necessitated design, development, and deployment of a nationwide infrastructure designed for sequestration, consolidation, and characterization of patient samples that disseminates de-identified information to public authorities in tight turnaround times. Here, we describe our development of such an infrastructure, which sequenced 594,832 high coverage SARS-CoV-2 genomes from isolates we collected in the United States (U.

Assessing the contributions of phylogenetic and environmental determinants of allergic cosensitization to fungi in humans.

Background: Understanding how allergies to 1 environmental fungus can lead to cosensitization to related fungi is important for the clinical management of allergies. Cosensitization can be caused by monosensitization combined with antibody cross-reactivity, or by coexposures driving independent sensitizations. A pioneering study showed that patterns of IgE cosensitization among 17 fungal species mirror fungal phylogeny.

Fungal allergen sensitization: Prevalence, risk factors, and geographic variation in the United States.

Background: Many fungal species are associated with the pathogenesis of allergic disease, yet most epidemiologic studies on IgE-mediated fungal sensitization have only included a few species.

Objective: We investigated fungal allergen sensitization prevalence, risk factors, and geographic variation in the United States.

Methods: From 2014 to 2019, a total of 7,912,504 serum-specific IgE (sIgE) test results for 17 fungal species were measured in 1,651,203 patients aged 0-85 years by a US-wide clinical laboratory.

Clinical characterization of the mutational landscape of 24,639 real-world samples from patients with myeloid malignancies.

Myeloid neoplasms represent a broad spectrum of hematological disorders for which somatic mutation status in key driver genes is important for diagnosis, prognosis and treatment. Here we summarize the findings of a targeted, next generation sequencing laboratory developed test in 24,639 clinical myeloid samples. Data were analyzed comprehensively and as part of individual cohorts specific to acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myeloproliferative neoplasms (MPN).

SARS-CoV-2 spike-protein targeted serology test results and their association with subsequent COVID-19-related outcomes.

Importance: In the absence of evidence of clinical utility, the United States' Centers for Disease Control and Prevention does not currently recommend the assessment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike-protein antibody levels. Clinicians and their patients, especially immunocompromised patients, may benefit from an adjunctive objective clinical laboratory measure of risk, using SARS-CoV-2 serology.

Objective: The aim of this study is to estimate the association between SARS-CoV-2 spike-protein targeted antibody levels and clinically relevant outcomes overall and among clinically relevant subgroups, such as vaccine and immunocompetency statuses.

Chronic Kidney Disease Testing Among At-Risk Adults in the U.S. Remains Low: Real-World Evidence From a National Laboratory Database.

Objective: An estimated 37 million Americans have chronic kidney disease (CKD). Nearly 90% do not know about their condition because of low awareness about the importance of CKD testing and diagnosis among practitioners and people at risk for CKD. This study uses data from a national clinical laboratory to identify guideline-recommended CKD testing rates across the U.

A population-based analysis of the longevity of SARS-CoV-2 antibody seropositivity in the United States.

Background: This cross-sectional study aimed to track population-based SARS-CoV-2 antibody seropositivity duration across the United States using observational data from a national clinical laboratory registry of patients tested by nucleic acid amplification (NAAT) and serologic assays. Knowledge of antibody seropositivity and its duration may help dictate post-pandemic planning.

Methods: Using assays to detect antibodies to either nucleocapsid () or spike () proteins performed on specimens from 39,086 individuals with confirmed positive COVID-19 by reverse transcription-polymerase chain reaction (RT-PCR) from March 2020 to January 2021, we analyzed nationwide seropositivity rates of IgG up to 300 days following patients' initial positive NAAT test.

A customized scaffolds approach for the detection and phasing of complex variants by next-generation sequencing.

Next-generation sequencing (NGS) is widely used in genetic testing for the highly sensitive detection of single nucleotide changes and small insertions or deletions. However, detection and phasing of structural variants, especially in repetitive or homologous regions, can be problematic due to uneven read coverage or genome reference bias, resulting in false calls. To circumvent this challenge, a computational approach utilizing customized scaffolds as supplementary reference sequences for read alignment was developed, and its effectiveness demonstrated with two CBS gene variants: NM_000071.

Exploring the landscape of pathogenic genetic variation in the ExAC population database: insights of relevance to variant classification.

Purpose: We evaluated the Exome Aggregation Consortium (ExAC) database as a control cohort to classify variants across a diverse set of genes spanning dominant and recessively inherited disorders.

Methods: The frequency of pathogenic variants in ExAC was compared with the estimated maximal pathogenic allele frequency (MPAF), based on the disease prevalence, penetrance, inheritance, allelic and locus heterogeneity of each gene. Additionally, the observed carrier frequency and the ethnicity-specific variant distribution were compared between ExAC and the published literature.

The COMBREX project: design, methodology, and initial results.

Experimental data exists for only a vanishingly small fraction of sequenced microbial genes. This community page discusses the progress made by the COMBREX project to address this important issue using both computational and experimental resources.

Edge-count probabilities for the identification of local protein communities and their organization.

We present a computational approach based on a local search strategy that discovers sets of proteins that preferentially interact with each other. Such sets are referred to as protein communities and are likely to represent functional modules. Preferential interaction between module members is quantified via an analytical framework based on a network null model known as the random graph with given expected degrees.

Predicting protein function from protein/protein interaction data: a probabilistic approach.

Motivation: The development of experimental methods for genome scale analysis of molecular interaction networks has made possible new approaches to inferring protein function. This paper describes a method of assigning functions based on a probabilistic analysis of graph neighborhoods in a protein-protein interaction network. The method exploits the fact that graph neighbors are more likely to share functions than nodes which are not neighbors.