Biology subjects

Mikes, J.

Publications and source records attributed to Mikes, J..

9 recordsLinked to original sources

bioRxiv2026

Systems-level longitudinal immune profiling reveals individualized immunotypes and genetic associations

The human immune system exhibits substantial inter-individual variation, yet how this variability is coordinated across the system and persists over time remains incompletely defined. Here, we integrated whole-genome sequencing with longitudinal multi-omics immune profiling in 101 healthy individuals followed over two years, combining mass cytometry-based immune cell profiling, PBMC transcriptomics, plasma proteomics, and clinical measurements. Coordinated variation across cellular composition, gene expression, and circulating proteins revealed reproducible immune patterns within individuals across visits. Integrative analyses identified three major immunotypes: adaptive lymphoid (CD4 T cell and B cell enriched), myeloid-inflammation (monocyte and dendritic cell-driven), and cytotoxic (CD8 T cell-dominated), each associated with distinct metabolic and inflammatory profiles. Genome-wide association analyses identified cell-type-specific quantitative trait loci primarily affecting memory lymphocytes, and a polygenic score for memory B cells correlated with both cellular abundance and transcriptional activity. Together, these findings provide a systems-level view for understanding baseline immune heterogeneity in human populations. TeaserLongitudinally stable immune individuality reflects coordinated modules shaped by systemic physiology and genetics

systems biology↗

bioRxiv2024

High-throughput analysis of membrane fluidity unveils a hidden dimension in immune cell states

Cell membranes undergo biophysical remodelling as an adaptation to the surroundings and to perform specific biological functions. However, the extent and relevance of such changes in human immune cells remain unknown, largely due to the lack of single-cell and multidimensional methodologies. Here, we apply a cytometry-based method to fill this gap by combining biophysical profiling with simultaneous analysis of immune cell markers. This platform reveals notable cell type-dependent plasma membrane order heterogeneity in immune cells. By sorting immune cells according to their membrane order and performing transcriptome and spatial surface proteome analyses together with functional tests, we show that plasma membrane order can be used to identify subsets of immune cells with distinct phenotypes and functional behaviours. Our findings demonstrate a broad heterogeneity of plasma membrane order in immune cells that will provide a more precise definition of immune cell states based on their biophysical properties in health and disease.

biophysics↗

bioRxiv2023

Scalable in-vitro immunostimulation of human blood for in-depth profiling of acute immune response effects

In-vitro immune stimulation of whole blood has great analytic potential for exploring the immune system function. However, logistical and biological constraints might limit the extent to which such investigations can be performed. Flexible and often even low-tech mobile applicability can increase the diversity of conditions that can be investigated. To this end, we developed and optimized a medium that enables prolonged in-vitro stimulation and enables highly functional immune responses within 24 hours of incubation. In addition, we also developed and optimized a low-tech water-based mobile incubator to enable logistical flexibility. Finally, we describe the implementation of both systems using a practical example of sample collection at a sampling site with no access to laboratory equipment outside of a research lab.

immunology↗

bioRxiv2020

Bifidobacteria-mediated immune system imprinting early in life

Immune-microbe interactions early in life influence an individuals risk of developing allergies, asthma and some autoimmune disorders. Breastfeeding helps guide the development of healthy immune-microbe relationships, in part by providing nutrients to specialized microbes that in turn benefit the host and its developing immune system. Such bacteria having co-evolved with humans are associated with reduced risks of immune mediated diseases but are increasingly rare in modern societies. Here we map an immunological sequence of events, triggered by microbial colonization that distinguish children with different gut bacterial composition. Lack of bifidobacterial species is associated with elevated markers of intestinal inflammation and immune dysregulation and in a randomized trial of breastfed infants, the infant-adapted Bifidobacterium infantis EVC001 silenced intestinal Th2 and Th17 immune responses, while inducing IFN{beta}, and its metabolites skew T-cell polarization in vitro, from Th2 towards Th1, suggesting a healthier immune imprinting during the first critical months of life. HIGHLIGHTSAn ordered sequence of immune changes after birth, driven by microbial interactions Low gut Bifidobacterium abundance is associated with markers of intestinal inflammation Feeding B. infantis EVC001 silenced intestinal Th2 and Th17 but upregulates IFN{beta} B. infantis EVC001 metabolites and/or enteric cytokines skew naive T-cell polarization towards Th1 and away from Th2

immunology↗

bioRxiv2020

Single-cell classification using learned cell phenotypes

Single-cell methods such as flow cytometry, Mass cytometry and single-cell mRNA sequencing collect high-dimensional data on thousands to millions of individual cells. An important aim during the analysis of such data is to classify cells into known categories and cell types. One commonly used approach towards this is clustering of cells with similar features followed by manual annotation of clusters in relation to known biology. A second approach, commonly used for cytometry data relies on manual sorting or "gating" of cells, often based on pairwise combinations of measurements used in a stepwise and very tedious process of cell annotation. Both of these approaches require manual inspection and annotation of every new dataset generated, a process that is not only time consuming but also subjective and surely influential for the conclusions drawn. The manual annotation is also difficult to reproduce by other researchers with a different perception of features that signify their cells of interest. Here we propose an alternative strategy based on machine learning of known phenotypes from manually curated, high-dimensional data and thereby enabling rapid classification of subsequent datasets in a more reproducible manner. This simple approach increases both throughput, reproducibility and simplicity of cell classification in single-cell biology.

immunology↗

bioRxiv2020

Achieving symptom relief in patients with Myalgic encephalomyelitis by targeting the neuro-immune interface and inducing disease tolerance

Myalgic encephalomyelitis, ME, previously also known as chronic fatigue syndrome (CFS) is a heterogeneous, debilitating syndrome of unknown etiology responsible for long-lasting disability in millions of patients worldwide. The most well-known symptom of ME is post-exertional malaise, but many patients also experience autonomic dysregulation, cranial nerve dysfunction and signs of immune system activation. Many patients also report a sudden onset of disease following an infection. The brainstem is a suspected focal point in ME pathogenesis and patients with structural impairment to the brainstem often show ME-like symptoms. The brainstem is also where the vagus nerve originates, a critical neuro-immune interface and mediator of the inflammatory reflex which regulate systemic inflammation. Here we report the results of a randomized, placebo-controlled trial using intranasal mechanical stimulation (INMEST) targeting the vagus nuclei, and higher centers in the brain of ME-patients and induce a sustainable, [~]30% reduction in overall symptom scores after eight weeks of treatment. By performing longitudinal, systems-level monitoring of the blood immune system in these patients, we uncover chronic immune activation in ME, as well as immunological correlates of improvement that center around the IL-17 axis, gut-homing immune cells and reduced inflammation. The mechanisms of symptom relief remains to be determined, but transcriptional analyses suggest an upregulation of disease tolerance mechanisms. We wish for these results to bring some hope to patients suffering from ME and inspire researchers to help test our new hypothesis that ME is a condition caused by a failure of inducing disease tolerance upon infection and persistent immune activation.

immunology↗

bioRxiv2020

Human immune system variation during one year

The human immune system varies extensively between individuals, but variation within individuals over time has not been well characterized. Systems-level analyses allow for simultaneous quantification of many interacting immune system components, and the inference of global regulatory principles. Here we present a longitudinal, systems-level analysis in 99 healthy adults, 50 to 65 years of age and sampled every 3rd month during one year. We describe the structure of inter-individual variation and characterize extreme phenotypes along a principal curve. From coordinated measurement fluctuations, we infer relationships between 115 immune cell populations and 750 plasma proteins constituting the blood immune system. While most individuals have stable immune systems, the degree of longitudinal variability is an individual feature. The most variable individuals, in the absence of overt infections, exhibited markers of poor metabolic health suggestive of a functional link between metabolic and immunologic homeostatic regulation. HIGHLIGHTSLongitudinal variation in immune cell composition during one year Inter-individual variation can be described along a principal curve Immune cell and protein relationships are inferred Variability over time is an individual feature correlating with markers of poor metabolic health

immunology↗

bioRxiv2019

Systems-level immunomonitoring using self-sampled capillary blood

Comprehensive profiling of the human immune system in patients with cancer, autoimmune disease and during infections are providing valuable information that help us understand disease states and discriminate productive from inefficient immune responses and identify possible targets for immune modulation. Recent technical advances now allow for all immune cell populations and hundreds of plasma proteins to be detected using small volume blood samples. To democratize such systems-immunological analyses, further simplified blood sampling and preservation will be important. Here we describe that blood obtained via a nearly painless self-sampling device of 100 microliter of capillary blood that is preserved and frozen, can simplify systems-level immunomonitoring studies.

immunology↗

bioRxiv2017

STRT-seq-2i: dual-index 5′ single cell and nucleus RNA-seq on an addressable microwell array

Single-cell RNA-seq has become routine for discovering cell types and revealing cellular diversity, but currently no high-throughput platform has been used successfully on archived human brain samples. We present STRT-seq-2i, an addressable 9600-microwell array platform, combining sampling by limiting dilution or FACS, with imaging and high throughput at competitive cost. We applied the platform to fresh single mouse cortical cells and to frozen post-mortem human cortical nuclei, matching the performance of a previous lower-throughput platform.

molecular biology↗