Phage-display immunoprecipitation sequencing of the antibody epitope repertoire in inflammatory bowel disease reveals distinct antibody signatures.

Inflammatory bowel diseases (IBDs), e.g., Crohn's disease (CD) and ulcerative colitis (UC), are chronic immune-mediated inflammatory diseases.

Phage display sequencing reveals that genetic, environmental, and intrinsic factors influence variation of human antibody epitope repertoire.

Phage-displayed immunoprecipitation sequencing (PhIP-seq) has enabled high-throughput profiling of human antibody repertoires. However, a comprehensive overview of environmental and genetic determinants shaping human adaptive immunity is lacking. In this study, we investigated the effects of genetic, environmental, and intrinsic factors on the variation in human antibody repertoires.

Allergenic food protein consumption is associated with systemic IgG antibody responses in non-allergic individuals.

Although food-directed immunoglobulin E (IgE) has been studied in the context of allergies, the prevalence and magnitude of IgG responses against dietary antigens are incompletely characterized in the general population. Here, we measured IgG binding against food and environmental antigens obtained from allergen databases and the immune epitope database (IEDB), represented in a phage displayed library of 58,233 peptides. By profiling blood samples of a large cohort representing the average adult Israeli population (n = 1,003), we showed that many food antigens elicited systemic IgG in up to 50% of individuals.

BIPS-A code base for designing and coding of a Phage ImmunoPrecipitation Oligo Library.

BIPS (Build Phage ImmunoPrecipitation Sequencing library) is a software that converts a list of proteins into a custom DNA oligonucleotide library for the PhIP-Seq system. The tool creates constant-length oligonucleotides with internal barcodes, while maintaining the original length of the peptide. This allows using large libraries, of hundreds of thousands of oligonucleotides, while saving on the costs of sequencing and maintaining the accuracy of oligonucleotide reads identification.

Head-to-head efficacy and safety of rivaroxaban, apixaban, and dabigatran in an observational nationwide targeted trial.

Aims: The advantages of direct oral anticoagulants (DOACs) over warfarin are well established in atrial fibrillation (AF) patients, however, studies that can guide the selection between different DOACs are limited. The aim was to compare the clinical outcomes of treatment with apixaban, rivaroxaban, and dabigatran in patients with AF.

Methods And Results: We conducted a retrospective, nationwide, propensity score-matched-based observational study from Clalit Health Services.

Systemic antibody responses against human microbiota flagellins are overrepresented in chronic fatigue syndrome patients.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease with an unclear etiology and pathogenesis. Both an involvement of the immune system and gut microbiota dysbiosis have been implicated in its pathophysiology. However, potential interactions between adaptive immune responses and the microbiota in ME/CFS have been incompletely characterized.

Estimating heritability of glycaemic response to metformin using nationwide electronic health records and population-sized pedigree.

Background: Variability of response to medication is a well-known phenomenon, determined by both environmental and genetic factors. Understanding the heritable component of the response to medication is of great interest but challenging due to several reasons, including small study cohorts and computational limitations.

Methods: Here, we study the heritability of variation in the glycaemic response to metformin, first-line therapeutic agent for type 2 diabetes (T2D), by leveraging 18 years of electronic health records (EHR) data from Israel's largest healthcare service provider, consisting of over five million patients of diverse ethnicities and socio-economic background.

Cross-reactive antibodies against human coronaviruses and the animal coronavirome suggest diagnostics for future zoonotic spillovers.

The spillover of animal coronaviruses (aCoVs) to humans has caused SARS, MERS, and COVID-19. While antibody responses displaying cross-reactivity between SARS-CoV-2 and seasonal/common cold human coronaviruses (hCoVs) have been reported, potential cross-reactivity with aCoVs and the diagnostic implications are incompletely understood. Here, we probed for antibody binding against all seven hCoVs and 49 aCoVs represented as 12,924 peptides within a phage-displayed antigen library.

Population-wide diversity and stability of serum antibody epitope repertoires against human microbiota.

Serum antibodies can recognize both pathogens and commensal gut microbiota. However, our current understanding of antibody repertoires is largely based on DNA sequencing of the corresponding B-cell receptor genes, and actual bacterial antigen targets remain incompletely characterized. Here we have profiled the serum antibody responses of 997 healthy individuals against 244,000 rationally selected peptide antigens derived from gut microbiota and pathogenic and probiotic bacteria.

A Prediction Model to Prioritize Individuals for a SARS-CoV-2 Test Built from National Symptom Surveys.

Background: The gold standard for COVID-19 diagnosis is detection of viral RNA through PCR. Due to global limitations in testing capacity, effective prioritization of individuals for testing is essential.

Methods: We devised a model estimating the probability of an individual to test positive for COVID-19 based on answers to 9 simple questions that have been associated with SARS-CoV-2 infection.

Estimating variance components in population scale family trees.

The rapid digitization of genealogical and medical records enables the assembly of extremely large pedigree records spanning millions of individuals and trillions of pairs of relatives. Such pedigrees provide the opportunity to investigate the sociological and epidemiological history of human populations in scales much larger than previously possible. Linear mixed models (LMMs) are routinely used to analyze extremely large animal and plant pedigrees for the purposes of selective breeding.

Environment dominates over host genetics in shaping human gut microbiota.

Human gut microbiome composition is shaped by multiple factors but the relative contribution of host genetics remains elusive. Here we examine genotype and microbiome data from 1,046 healthy individuals with several distinct ancestral origins who share a relatively common environment, and demonstrate that the gut microbiome is not significantly associated with genetic ancestry, and that host genetics have a minor role in determining microbiome composition. We show that, by contrast, there are significant similarities in the compositions of the microbiomes of genetically unrelated individuals who share a household, and that over 20% of the inter-person microbiome variability is associated with factors related to diet, drugs and anthropometric measurements.

Prevention strategy of hepatitis B virus infection among the Ethiopian community in Israel.

Between 1980 and 1985, over 16,000 immigrants from Ethiopia, a population at high risk for hepatitis B virus (HBV) infection, arrived in Israel. The present study was designed to provide epidemiological information necessary for developing prevention strategies against HBV infection. Among the 144 subjects studied in an absorption center in Israel, only 32% had no detectable HBV markers and were therefore susceptible to infection.