Biology subjects

Wuyts, S.

Publications and source records attributed to Wuyts, S..

7 recordsLinked to original sources

bioRxiv2026

A global genomic survey of prokaryotic carbon fixation reveals an oxygen-tolerant rTCA cycle in the surface ocean

Autotrophic carbon fixation, the conversion of inorganic carbon into biomass, underpins life on Earth. Prokaryotes can carry out this process via at least seven biochemically distinct pathways, yet the phylogenetic and environmental distribution of most remains poorly resolved. Screening approximately 40 billion genes from reference genomes, metagenome-assembled genomes (MAGs) and unbinned metagenomic contigs, we provide a global assessment of the phylogeny and ecophysiology of prokaryotic autotrophs. Most pathway marker genes occurred in unbinned contigs and low-quality MAGs, representing phylogenetically distinct lineages absent from isolate genomes and quality filtered MAGs. Established autotrophs accounted for the large majority of pathway detections in quality filtered MAGs, largely recapitulating known biology from cultivated model organisms. Against this backdrop, the reductive TriCarboxylic Acid (rTCA) cycle, long considered restricted to anoxic environments, was detected in three phylogenetically distinct Campylobacterota lineages from oxygenated surface seawater, suggesting a previously unrecognized and unexpected niche for this pathway. We show that all three MAGs share an enzyme variant, previously described in other oxygen-tolerant lineages, that likely underlies their presence in the oxygenated surface ocean. Read mapping across global ocean metagenomes indicates that the organisms carrying it could be far more widespread than the scarcity of recovered MAGs alone would suggest. Together, these findings illustrate that the current view of global autotrophic carbon fixation is largely shaped by what genome-resolved methods can readily recover, while the true phylogenetic and ecological distribution of autotrophic carbon fixation appears to be much broader.

microbiology↗

bioRxiv2026

IMMREP25: Unseen Peptides

T cell receptors (TCRs) can bind to peptides presented by MHC molecules (pMHC) as a first step to trigger a T cell response. Reliable approaches to predict TCR:pMHC binding would have broad applications in clinical diagnostics, therapeutics, and the fundamental understanding of molecular interactions. IMMREP is a community organized series of prediction contests that asks participants to predict TCR:pMHC binding on unpublished datasets. Previous iterations in 2022 and 2023 showed multiple approaches can predict TCR-pMHC binding with significant accuracy (median AUC_0.1[≥]0.7) for peptides where experimental data is available ("seen" peptides). In contrast, models did not outperform random guessing for peptides that have no such data available ("unseen" peptides). Here we report on the results of IMMREP25, which focused solely on unseen peptides in order to evaluate the cutting edge of the field. We received 126 named submissions predicting the specificity of 1,000 TCRs against twenty unseen peptides restricted by one of two MHC molecules (HLA-A*02:01 and HLA-B*40:01). The best performing methods showed a macro-AUC_0.1 of 0.60, significantly better than random, demonstrating significant advances in the field. The top performing methods incorporated structural modeling into their approach, indicating that especially for unseen peptides, a structural understanding aids in the prediction of TCR:pMHC interactions. The results from this benchmark highlight the significant challenges remaining for TCR:pMHC predictions and will inform future method development.

bioinformatics↗

bioRxiv2026

Applications of T-cell receptor specificity annotation models for quality control and immunomonitoring in adoptive T-cell therapies

Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is a powerful candidate immunotherapy. However, the personalized production process that underlies its potential also introduces an element of stochasticity, where the actual target of the TILs is variable across patients and protocols, and remains largely unknown. In this letter, we describe the application of T-cell receptor (TCR) sequencing in combination with computational tools for annotating epitope-specificity of the TCR repertoire of TIL products as a potent quality control. We highlight the potential of this approach by demonstrating the tumor antigen-specificity of TCR clusters within the TIL product in silico, and validating these responses in vitro. We also demonstrate screening for off-cancer reactivity against viral antigens, and immune monitoring of identified TCR clones. HighlightsO_LIT-cell receptor sequencing combined with epitope annotation tools are viable for quality control of TIL products by identifying tumor-specific clones. C_LIO_LIWe showed the additional utility of screening for off-cancer reactivity, such as viral antigens. C_LIO_LIThe identified tumor-specific TCR clones can be tracked in vivo providing a means of immune monitoring. C_LI

bioinformatics↗

bioRxiv2023

Consistency across multi-omics layers in a drug-perturbed gut microbial community

Multi-omics analyses are increasingly employed in microbiome studies to obtain a holistic view of molecular changes occurring within microbial communities exposed to different conditions. However, it is not always clear to what extent each omics data type contributes to our understanding of the community dynamics and whether they are concordant with each other. Here we map the molecular response of a synthetic community of 32 human gut bacteria to three non-antibiotic drugs by using five omics layers, namely 16S rRNA gene profiling, metagenomics, metatranscriptomics, metaproteomics, and metabolomics. Using this controlled setting, we find that all omics methods with species resolution in their readouts are highly consistent in estimating relative species abundances across conditions. Furthermore, different omics methods complement each other in their ability to capture functional changes in response to the drug perturbations. For example, while nearly all omics data types captured that the antipsychotic drug chlorpromazine selectively inhibits Bacteroidota representatives in the community, the metatranscriptome and metaproteome suggested that the drug induces stress responses related to protein quality control and metabolomics revealed a decrease in polysaccharide uptake, likely caused by Bacteroidota depletion. Taken together, our study provides insights into how multi-omics datasets can be utilised to reveal complex molecular responses to external perturbations in microbial communities.

microbiology↗

bioRxiv2019

Comparative genome analysis of Lactobacillus mudanjiangensis, an understudied member of the Lactobacillus plantarum group

The genus Lactobacillus is known to be extremely diverse and consists of different phylogenetic groups that show a diversity roughly equal to the expected diversity of a typical bacterial genus. One of the most prominent phylogenetic groups within this genus is the Lactobacillus plantarum group which contains the understudied Lactobacillus mudanjiangensis species. Before this study, only one L. mudanjiangensis strain, DSM 28402T, was described but without whole-genome analysis. In this study, three strains classified as L. mudanjiangensis, were isolated from three different carrot juice fermentations and their whole-genome sequence was determined, together with the genome sequence of the type strain. The genomes of all four strains were compared with publicly available L. plantarum group genome sequences. This analysis showed that L. mudanjiangensis harbored the second largest genome size and gene count of the whole L. plantarum group. In addition, all members of this species showed the presence of a gene coding for a putative cellulose-degrading enzyme. Finally, three of the four L. mudanjiangensis strains studied showed the presence of pili on scanning electron microscopy (SEM) images, which were linked to conjugative gene regions, coded on plasmids in at least two of the strains studied. Author summaryLactobacillus mudanjiangensis is an understudied species within the Lactobacillus plantarum group. Since its first description, no other studies have reported its isolation. Here, we present the first four genome sequences of this species, which include the genome sequence of the type strain and three new L. mudanjiangensis strains isolated from fermented carrot juice. The genomes of all four strains were compared with publicly available L. plantarum group genome sequences. We found that this species harbored the second largest genome size and gene count of the whole L. plantarum group. Furthermore, we present the first scanning electron microscopy (SEM) images of L. mudanjiangensis, which showed the formation of pili in three strains that we linked to genes related to conjugation. Finally, we found the presence of a unique putative cellulose-degrading enzyme, opening the door for different industrial applications of these Lactobacillus strains.

microbiology↗

bioRxiv2019

A genome-based species taxonomy of the Lactobacillus Genus Complex

BackgroundThere are over 200 published species within the Lactobacillus Genus Complex (LGC), the majority of which have sequenced type strain genomes available. Although gold standard, genome-based species delimitation cutoffs are accepted by the community, they are seldom checked against currently available genome data. In addition, there are many species-level misclassification issues within the LGC. We constructed a de novo species taxonomy for the LGC based on 2,459 publicly available, decent-quality genomes and using a 94% core nucleotide identity threshold. We reconciled these de novo species with published species and subspecies names by (i) identifying genomes of type strains in our dataset and (ii) performing comparisons based on 16S rRNA sequence identity against type strains. ResultsWe found that genomes within the LGC could be divided into 239 clusters (de novo species) that were discontinuous and exclusive. Comparison of these de novo species to published species lead to the identification of ten sets of published species that can be merged and one species that can be split. Further, we found at least eight genome clusters that constitute new species. Finally, we were able to accurately classify 98 unclassified genomes and reclassify 74 wrongly classified genomes. ConclusionsThe current state of LGC species taxonomy is largely consistent with genome data, but there are some inconsistencies as well as genome misclassifications. These inconsistencies should be resolved to evolve towards a meaningful taxonomy where species have a consistent size in terms of sequence divergence.

bioinformatics↗

bioRxiv2018

Topical cream with live lactobacilli modulates the skin microbiome and reduce acne symptoms

The skin is home to an important part of our commensal microbiota, despite it being a cool, acidic and desiccated environment. Tailored microbiome modulation approaches with, for example probiotics, are highly challenging for this body site. Here we show by next-generating sequencing that Lactobacillus taxa -especially those known to be dominant in the human vagina- are underestimated members of the skin microbiota. Specific Lactobacillus strains were selected in the lab and formulated in a viable form in an oil in water-based topical cream. Facial application by patients with mild-to-moderate acne symptoms was able to reduce inflammatory lesions and comedone formation. This was associated with a temporary modulation of the skin microbiome, including a reduction in relative abundance of staphylococci and an increase in lactobacilli. Skin microbiome modulation by addition of carefully formulated lactobacilli seems to be new therapeutic option to reduce antibiotic use for common acne symptoms.

clinical trials↗