Biology subjects

Dobson, R. C. J.

Publications and source records attributed to Dobson, R. C. J..

5 recordsLinked to original sources

bioRxiv2026

The Celiac Microbiome Repository (CMR): A Curated Collection of Celiac Disease Gut Microbiome Sequencing Data

Celiac disease is an autoimmune condition where the gut microbiome is increasingly recognised as a key environmental factor. While high-throughput sequencing has led to a surge in celiac-related gut microbiome profiling data, these datasets remain fragmented, heterogeneous, and often lack the metadata required for large-scale integration into pooled, cross-cohort datasets. To address this, we developed the Celiac Microbiome Repository (CMR), a curated, open-access collection of celiac-related 16S rRNA gene and shotgun metagenomic sequencing datasets. We employed a systematic curation workflow to identify datasets across the NCBI Sequence Read Archive (SRA) and Scopus, followed by manual metadata extraction and direct author engagement. All 16S data was reprocessed through DADA2 and shotgun data through MetaPhlAn4 to facilitate comparison across studies. The CMR version 1.0 comprises 28 datasets containing 3,245 samples from 13 countries and 5 body sites. Our analysis reveals that while publicly available celiac microbiome samples have accumulated at a rate of approximately 140 per year, significant barriers to accessibility exist. Just 20 of 58 eligible datasets were found to have both raw data and essential metadata readily available within public archives. The repository features a dual-interface design, consisting of a GitHub backend for programmatic access and an R Shiny frontend for interactive data exploration. By providing this curated and harmonised resource, the CMR enables the research community to leverage public data for global meta-analyses and machine learning applications. Ultimately, this work provides the foundation needed to move beyond isolated, small-scale studies toward high-powered discoveries in celiac disease research. Database URLs: https://github.com/CeliacMicrobiomeRepo/celiac-repository | https://celiac.shinyapps.io/celiac-webapp

bioinformatics↗

bioRxiv2026

Micro16S: Universal Phylogenetic 16S rRNA Gene Representations for Deep Learning of the Microbiome

1Existing self-supervised microbiome models represent taxa as discrete, independent units restricted to fixed vocabularies, disregarding their evolutionary context. Here we present Micro16S, a deep learning approach that embeds 16S ribosomal RNA gene sequences into a continuous vector space according to phylogenetic relationships derived from the Genome Taxonomy Database. Using a combination of triplet and pair loss objectives, the model learns representations where spatial proximity reflects phylogenetic relatedness, while remaining largely invariant to the specific 16S rRNA region. Evaluations demonstrate taxonomically coherent clustering across most ranks and substantially improved region invariance compared to k-mer frequency baselines. A transformer pretrained on 50,418 unlabelled gut microbiome samples using these embeddings captured biologically meaningful community structure, though classical machine learning baselines outperformed Micro16S across six benchmark classification tasks, highlighting the limitations of the current system. These results establish the feasibility of phylogenetic embeddings for microbiome deep learning and identify mining algorithm design and class imbalance as primary targets for future improvement.

bioinformatics↗

bioRxiv2023

Genetic drift and genome reduction in the plant pathogen Candidatus Liberibacter solanacearum shapes a new enzyme in lysine biosynthesis.

The effect of population bottlenecks and genome reduction on enzyme function is poorly understood. Candidatus Liberibacter solanacearum is a bacterium with a reduced genome that is transmitted vertically to the egg of an infected psyllid--a population bottleneck that imposes genetic drift and is predicted to affect protein structure and function. Here, we define the effects of genome reduction and genetic drift on the function of Ca. L. solanacearum dihydrodipicolinate synthase (CLsoDHDPS), which catalyses the committed branchpoint reaction in diaminopimelate and lysine biosynthesis. We demonstrate that CLsoDHDPS is expressed in Ca. L. solanacearum and expression is increased [~]2-fold in the insect host compared to in planta. CLsoDHDPS has increased aggregation propensity, implying mutations have destabilised the enzyme but are compensated for through elevated chaperone expression and a stabilised oligomeric state. CLsoDHDPS uses a ternary-complex kinetic mechanism, which is unique among DHDPS enzymes, has unusually low catalytic ability, but an unusually high substrate affinity. Structural studies demonstrate that the active site is more open, and the structure of CLsoDHDPS with both pyruvate and the substrate analogue succinic-semialdehyde reveals that the product is both structurally and energetically different and therefore evolution has in this case fashioned a new enzyme. Our study reveals the effects of genome reduction and genetic drift on the function of essential enzymes and provides insights on bacteria-host co-evolutionary association. We suggest that bacteria with endosymbiotic lifestyles present a rich vein of interesting enzymes useful for understanding enzyme function and/or informing protein engineering efforts.

evolutionary biology↗

bioRxiv2020

Mechanism of NanR gene repression and allosteric induction of bacterial sialic acid metabolism

Bacteria respond to environmental changes by inducing transcription of some genes and repressing others. Sialic acids, which coat human cell surfaces, are a nutrient source for pathogenic and commensal bacteria. The Escherichia coli GntR-type transcriptional repressor, NanR, regulates sialic acid metabolism, but the mechanism is unclear. Here, we demonstrate that three NanR dimers bind a (GGTATA)3-repeat operator cooperatively and with high affinity. Truncation of an N-terminal extension abolishes cooperative binding. The effector, N-acetylneuraminate, binds NanR and attenuates DNA binding. Crystal structure data show that N-acetylneuraminate binding to NanR causes a domain rearrangement that locks the protein in a conformation that prevents DNA binding. Single-particle cryo-electron microscopy structures of NanR bound to DNA reveal the DNA binding domain is reorganized to engage DNA, while the three dimers assemble in close proximity across the (GGTATA)3-repeat operator allowing protein-protein interactions to form via the N-terminal extensions. Our data provides a molecular basis for the regulation of bacterial sialic acid metabolism.

molecular biology↗

bioRxiv2016

Structural and Functional analysis of the GABARAP Interaction Motif (GIM).

Through the canonical LC3 interaction motif (LIR), [W/F/Y]-X1-X2-[I/L/V], protein complexes are recruited to autophagosomes to perform their functions as either autophagy adaptors or receptors. How these adaptors/receptors selectively interact with either LC3 or GABARAP families remains unclear. Herein, we determine the range of selectivity of 30 known core LIR motifs towards LC3s and GABARAPs. From these, we define a GABARAP Interaction Motif (GIM) sequence (W/F-V-X2-V) that the adaptor protein PLEKHM1 tightly conforms to. Using biophysical and structural approaches, we show that the PLEKHM1-LIR is indeed eleven-fold more specific for GABARAP than LC3B. Selective mutation of the X1 and X2 positions either completely abolished the interaction with all LC3 and GABARAPs or increased PLEKHM1-GIM selectivity 20-fold towards LC3B. Finally, we show that conversion of the canonical p62/SQSTM1-LIR into our newly defined GIM, by introducing two valine residues, enhances p62/SQSTM1 interaction with endogenous GABARAP over LC3B. The identification of a GABARAP-specific interaction motif will aid the identification and characterization of the continually expanding array of autophagy receptor and adaptor proteins and their in vivo functions.

biochemistry↗