Biology subjects

Pesesky, M.

Publications and source records attributed to Pesesky, M..

3 recordsLinked to original sources

bioRxiv2025

Multi-centered T cell repertoire profiling identifies novel alterations in the immune repertoire of individuals with inflammatory bowel disease and validates previous findings

IntroductionIBD is an incurable immune-mediated inflammatory disease (IMID), affecting the gut with a high rate of primary- and secondary-loss-of-response to therapy. By investigating the T cell receptor repertoire of individuals with IBD, novel therapeutic and preventive strategies can be identified, and a better understanding of IBD can be obtained. MethodsWhereas most studies have so far focused on the more diverse T cell receptor beta (TRB) repertoire, we here profiled the alpha (TRA) repertoire of three cohorts containing treatment-naive and treated individuals in addition to individuals living with the disease for >20 years, resulting in an exhaustive dataset containing the TRA repertoire of 2,151 individuals. ResultsUsing the generated datasets, we were able to replicate previous findings describing the expansion of Crohns-associated invariant T (CAIT) cells in individuals with Crohns disease (CD) in the three cohorts. Using a hypothesis-free statistical testing framework, we identified clonotypes that were associated with the disease at its different stages, e.g., at the time of diagnosis and decades post-diagnosis. By conducting a meta-analysis across the three cohorts, we were able to identify a set of clonotypes that were associated with the disease regardless of its stage. We validated our findings in a previously published independent test dataset from a German cohort, showing the robustness of the identified sets of clonotypes. ConclusionThe identified clonotypes are potential novel therapeutic targets to treat IBD, e.g., through targeted depletion. These clonotypes are also of major interest as they can be investigated in a targeted fashion to identify culprit antigen(s) in IBD.

immunology↗

bioRxiv2024

Seq2MAIT: A Novel Deep Learning Framework for Identifying Mucosal Associated Invariant T (MAIT) Cells

Mucosal-associated invariant T (MAIT) cells are a group of unconventional T cells that mainly recognize bacterial vitamin B metabolites presented on MHC-related protein 1 (MR1). MAIT cells have been shown to play an important role in controlling bacterial infection and in responding to viral infections. Furthermore, MAIT cells have been implicated in different chronic inflammatory diseases such as inflammatory bowel disease and multiple sclerosis. Despite their involvement in different physiological and pathological processes, a deeper understanding of MAIT cells is still lacking. Arguably, this can be attributed to the difficulty of quantifying and measuring MAIT cells in different biological samples which is commonly done using flow cytometry-based methods and single-cell-based RNA sequencing techniques. These methods mostly require fresh samples which are difficult to obtain, especially from tissues, have low to medium throughput, and are costly and labor-intensive. To address these limitations, we developed sequence-to-MAIT (Seq2MAIT) which is a transformer-based deep neural network capable of identifying MAIT cells in bulk TCR-sequencing datasets, enabling the quantification of MAIT cells from any biological materials where human DNA is available. Benchmarking Seq2MAIT across different test datasets showed an average area-under-the-receiver-operator-curve (AU[ROC]) >0.80. In conclusion, Seq2MAIT is a novel, economical, and scalable method for identifying and quantifying MAIT cells in virtually any biological sample.

bioinformatics↗

bioRxiv2018

Adaptive strategies of the candidate probiotic E. coli Nissle in the mammalian gut

Probiotics are living microorganisms that are increasingly used as gastrointestinal therapeutics by virtue of their innate or engineered genetic function. Unlike abiotic therapeutics, probiotics can replicate in their intended site, subjecting their genomes and therapeutic properties to natural selection. By exposing the candidate probiotic E. coli Nissle (EcN) to the mouse gastrointestinal tract over several weeks, we uncovered the consequences of gut transit, inter-species competition, antibiotic pressure, and engineered genetic function on the processes under selective pressure during both within-genome and horizontal evolutionary modes. We then show the utility of EcN as a chassis for engineered function by achieving the highest reported reduction in serum phenylalanine levels in a mouse model of phenylketonuria using an engineered probiotic. Collectively, we demonstrate a generalizable pipeline which can be applied to other probiotic strains to better understand their safety and engineering potential.

evolutionary biology↗