Biology subjects

Rewers, M.

Publications and source records attributed to Rewers, M..

4 recordsLinked to original sources

bioRxiv2025

Differences in immune cell profiles around the time of islet autoimmunity seroconversion in children with and without type 1 diabetes

Seroconversion (SV) marks the initiation of islet autoimmunity (IA) and pre-clinical phase of type 1 diabetes, yet the contributions of immune cells beyond cytotoxic T cells remain unclear. We applied high-resolution immune cell-type deconvolution using peripheral blood DNA methylation data from nested case-control samples of the Diabetes Autoimmunity Study in the Young (DAISY; n=151) and The Environmental Determinants of Diabetes in the Young (TEDDY; n=166) to estimate immune cell proportions across pre-SV and SV timepoints and construct functional ratios, such as the neutrophil-to-lymphocyte ratio (NLR). Using linear models, we evaluated differences between type 1 diabetes cases and controls at pre-SV, SV, and the change across timepoints. Pre-SV, cases had higher NLR and lower CD4T/CD8T cell ratios. At SV, the combined B-CD4T-CD8T memory/naive ratio was reduced in cases. From pre-SV to SV, cases showed attenuations in NLR, B-memory/naive, and B-CD4T-CD8T memory/naive ratios. These patterns may reflect delayed or disrupted immune maturation with the persistence or expansion of naive cells or impaired transition to memory subsets following antigen exposure. Our findings highlight early shifts in innate and adaptive immune cell dynamics during type 1 diabetes pathogenesis and support immune cell ratios as potential biomarkers for risk stratification and mechanistic insight. Article HighlightsO_LIWe sought to examine immune cells around the time of IA seroconversion in children at higher risk for type 1 diabetes. C_LIO_LIWe wanted to answer whether immune cell ratio differences exist between type 1 diabetes cases and controls around IA at pre-SV, SV, and the change pre-SV to SV. C_LIO_LIWe found immune cell ratio differences between type 1 diabetes cases and controls before, during, and across SV timepoints, suggesting potential etiological and pathophysiological roles. C_LIO_LIOur findings highlight the complexity of immunodynamics around IA seroconversion and potential role for immune cell ratios in type 1 diabetes risk stratification and intervention. C_LI

immunology↗

bioRxiv2023

Phage-bacteria dynamics during the first years of life revealed by trans-kingdom marker gene analysis

Humans are colonized with commensal bacteria soon after birth, and, while this colonization is affected by lifestyle and other factors, bacterial colonization proceeds through well-studied phases. However, less is known about phage communities in early human development due to small study sizes, inability to leverage large databases, and lack of appropriate bioinformatics tools. In this study, whole genome shotgun sequencing data from the TEDDY study, composed of 12,262 longitudinal samples from 887 children in 4 countries, is reanalyzed to assess phage and bacterial dynamics simultaneously. Reads from these samples were mapped to marker genes from both bacteria and a new database of tens of thousands of phage taxa from human microbiomes. We uncover that each child is colonized by hundreds of different phages during the early years, and phages are more transitory than bacteria. Participants samples continually harbor new phage species over time whereas the diversification of bacterial species begins to saturate. Phage data improves the ability for machine learning models to discriminate samples by country. Finally, while phage populations were individual-specific, striking patterns arose from the larger dataset, showing clear trends of ecological succession amongst phages, which correlated well with putative host bacteria. Improved understanding of phage-bacterial relationships may reveal new means by which to shape and modulate the microbiome and its constituents to improve health and reduce disease, particularly in vulnerable populations where antibiotic use and/or other more drastic measures may not be advised.

microbiology↗

bioRxiv2023

Efficient encoding of large antigenic spaces by epitope prioritization with Dolphyn

We investigated a relatively underexplored component of the gut-immune axis by profiling the antibody response to gut phages using Phage Immunoprecipitation Sequencing (PhIP-Seq). To enhance this approach, we developed Dolphyn, a novel method that uses machine learning to select peptides from protein sets and compresses the proteome through epitope-stitching. Dolphyn improves the fraction of gut phage library peptides bound by antibodies from 10% to 31% in healthy individuals, while also reducing the number of synthesized peptides by 78%. In our study on gut phages, we discovered that the immune system develops antibodies to bacteria-infecting viruses in the human gut, particularly E.coli-infecting Myoviridae. Cost-effective PhIP-Seq libraries designed with Dolphyn enable the assessment of a wider range of proteins in a single experiment, thus facilitating the study of the gut-immune axis.

bioengineering↗

bioRxiv2018

Deconvoluting Virome-Wide Antiviral Antibody Profiling Data

The ability to comprehensively characterize exposures and immune responses to viral infections will be critical to better understanding human health and disease. We previously described the VirScan system, a phage-display based technology for profiling antibody binding to a comprehensive library of peptides designed to represent the human virome. The previous VirScan analytical approach did not fully account for disproportionate representation of viruses in the library or for antibody cross-reactivity among sequences shared by related viruses. Here we present the AntiViral Antibody Response Deconvolution Algorithm ( AVARDA), a multi-module software package for analyzing VirScan datasets. AVARDA provides a probabilistic assessment of infection at species-level resolution by considering alignment of all library peptides to each other and to all human viruses. We employed AVARDA to analyze VirScan data from a cohort of encephalitis patients with either known viral infections or undiagnosed etiologies. By comparing acute and convalescent sera, AVARDA successfully confirmed or detected antibody responses to human herpesviruses 1, 3, 4, 5, and 6, thereby improving the rate of diagnosing viral encephalitis in this cohort by 62.5%. We further assessed AVARDAs utility in the setting of an epidemiological study, demonstrating its ability to determine infections acquired in a child followed prospectively from infancy. We consider ways in which AVARDAs conceptual framework may be further developed in the future and describe how its analyses may be extended beyond investigations of viral infection. AVARDA, in combination with VirScan and other pan-pathogen serological techniques, is likely to find broad utility in the epidemiology and diagnosis of infectious diseases.

bioinformatics↗