publications

2024

1. ProCogGraph: A graph-based mapping of cognate ligand domain interactions

   Matthew Crown, and Matthew Bashton

   Bioinform. Adv., Oct 2024

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   Abstract Motivation Mappings of domain-cognate ligand interactions can enhance our understanding of the core concepts of evolution and be used to aid docking and protein design. Since the last available cognate-ligand domain database was released, the PDB has grown significantly and new tools are available for measuring similarity and determining contacts. Results We present ProCogGraph, a graph database of cognate-ligand domain mappings in PDB structures. Building upon the work of the predecessor database, PROCOGNATE, we use data-driven approaches to develop thresholds and interaction modes. We explore new aspects of domain-cognate ligand interactions, including the chemical similarity of bound cognate ligands and how domain combinations influence cognate ligand binding. Finally, we use the graph to add specificity to partial EC IDs, showing that ProCogGraph can complete partial annotations systematically through assigned cognate ligands. Availability and Implementation The ProCogGraph pipeline, database and flat files are available at https://github.com/bashton-lab/ProCogGraph and https://doi.org/10.5281/zenodo.13165851. Supplementary information Supplementary data are available at Bioinformatics Advances online.

2. TRIM7 ubiquitinates SARS-CoV-2 membrane protein to limit apoptosis and viral replication

   Maria Gonzalez-Orozco, Hsiang-Chi Tseng, Adam Hage, and 22 more authors

   bioRxivorg, Jun 2024

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   SARS-CoV-2 is a highly transmissible virus that causes COVID-19 disease. Mechanisms of viral pathogenesis include excessive inflammation and viral-induced cell death, resulting in tissue damage. We identified the host E3-ubiquitin ligase TRIM7 as an inhibitor of apoptosis and SARS-CoV-2 replication via ubiquitination of the viral membrane (M) protein. Trim7 -/- mice exhibited increased pathology and virus titers associated with epithelial apoptosis and dysregulated immune responses. Mechanistically, TRIM7 ubiquitinates M on K14, which protects cells from cell death. Longitudinal SARS-CoV-2 sequence analysis from infected patients revealed that mutations on M-K14 appeared in circulating variants during the pandemic. The relevance of these mutations was tested in a mouse model. A recombinant M-K14/K15R virus showed reduced viral replication, consistent with the role of K15 in virus assembly, and increased levels of apoptosis associated with the loss of ubiquitination on K14. TRIM7 antiviral activity requires caspase-6 inhibition, linking apoptosis with viral replication and pathology.

3. Environmental microbiome in the home and daycare settings during the COVID-19 pandemic, and potential risk of non-communicable disease in children

   Jill A McKay, Matthew Crown, Matthew Bashton, and 3 more authors

   Environ. Microbiol. Rep., Feb 2024

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   An exposure to diverse microbial population early in life is important for the development of immunity against various non-communicable diseases including asthma, childhood leukaemia and other cancers. Social mixing in daycare settings helps with exposure to a variety of microbes. However, social isolation and a high emphasis on workplace hygiene during the COVID pandemic may have affected children’s exposure to diverse microbiota. The structure of microbial communities and their role in developing immunity to various diseases are not well understood. In this study, we investigated the structure of microbial communities in daycare and home settings during the pandemic. Interestingly, microbial diversity was relatively higher in dust samples collected from homes, with human-associated taxa being more prevalent compared to those from daycare settings. Environmental microbes were more abundant in dust samples from daycare providers. These results potentially suggest that cleaning practices during the pandemic may have influenced the diversity and microbial abundance of the daycare samples. Several bacterial taxa detected in both the environments are known to induce anti-inflammatory and immunomodulatory responses, conferring protection from various diseases. Therefore, exposure to diverse microbial population in early childhood may play an important role in developing immunity against various non-communicable and infectious diseases.

4. OMEinfo: global geographic metadata for -omics experiments

   Matthew Crown, and Matthew Bashton

   Bioinform. Adv., Feb 2024

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   Summary: Microbiome studies increasingly associate geographical features like rurality and climate with microbiomes. It is essential to correctly integrate rich geographical metadata; and inconsistent definitions of rurality, can hinder cross-study comparisons. We address this with OMEinfo, a tool for automated retrieval of consistent geographical metadata from user-provided location data. OMEinfo leverages open data sources such as the Global Human Settlement Layer, and Open-Data Inventory for Anthropogenic Carbon dioxide. OMEinfo’s web-app enables users to visualize and investigate the spatial distribution of metadata features. OMEinfo promotes reproducibility and consistency in microbiome metadata through a standardized metadata retrieval approach. To demonstrate utility, OMEinfo is used to replicate the results of a previous study linking population density to bacterial diversity. As the field explores relationships between microbiomes and geographical features, tools like OMEinfo will prove vital in developing a robust, accurate, and interconnected understanding of these interactions, whilst having applicability beyond this field to any studies utilizing location-based metadata. Finally, we release the OMEinfo annotation dataset of 5.3 million OMEinfo annotated samples from the ENA, for use in retrospective analyses of sequencing samples, and suggest several ways researchers and sequencing read repositories can improve the quality of underlying metadata submitted to these public stores. Availability and implementation: OMEinfo is freely available and released under an MIT licence. OMEinfo source code is available at https://github.com/m-crown/OMEinfo/ and https://doi.org/10.5281/zenodo.10518763.

2022

1. SPEAR: Systematic ProtEin AnnotatoR

   Matthew Crown, Natália Teruel, Rafael Najmanovich, and 1 more author

   Bioinformatics, Aug 2022

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   SUMMARY: We present Systematic ProtEin AnnotatoR (SPEAR), a lightweight and rapid SARS-CoV-2 variant annotation and scoring tool, for identifying mutations contributing to potential immune escape and transmissibility (ACE2 binding) at point of sequencing. SPEAR can be used in the field to evaluate genomic surveillance results in real time and features a powerful interactive data visualization report. AVAILABILITY AND IMPLEMENTATION: SPEAR and documentation are freely available on GitHub: https://github.com/m-crown/SPEAR and are implemented in Python and installable via Conda environment. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

2021

1. Bacterial Diversity in House Dust: Characterization of a Core Indoor Microbiome

   Jonathan R Thompson, Ariadne Argyraki, Matthew Bashton, and 12 more authors

   Front. Environ. Sci. Eng. China, Aug 2021

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   Our indoor microbiome consists of a wide range of microbial taxa. Whilst many of these microbes are benign, some are beneficial, some harmful, yet our knowledge of the spatial heterogeneity of bacterial assemblages in our residential environment remains limited. To investigate the existence of a common core house dust bacterial microbiome we selected household vacuum dusts, collected through a citizen science approach, from homes across two bioclimatic regions (UK, Oceanic/Maritime and Greece, Mediterranean). Following the extraction of DNA from each dust sample, we targeted the bacterial 16S rRNA gene using Illumina NextSeq sequencing. PERMANOVA analysis of the microbial communities at family level grouped samples within their distinct bioclimatic region and SIMPER analysis at genus level identified the statistically significant taxa responsible for driving diversity between these groups. A “common to all” core house dust microbiome consisted of Acinetobacter, Massalia, Rubellimicrobium, Sphingomonas and Staphylococcus; genera typically associated with human occupancy and common environmental sources. Additionally, a “unique location specific” microbiome was identified, reflective of the bioclimatic region. The Greek dusts indicated a lower average diversity than the UK house dusts, with a high abundance of Rhizobiaceae in the Greek samples. Our study highlights citizen science as a powerful approach to access the indoor residential environment, at scale, and establishes the existence of a “core” house dust microbiome independent of bioclimatic region.