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Biology subjects

Davies, R. M.

Publications and source records attributed to Davies, R. M..

6 recordsLinked to original sources

The mechanism of biofilm degradation by a detachable tailspike of gene transfer agents

Gene transfer agents (GTAs) are phage-derived elements that have evolved repeatedly across diverse prokaryotes, where they drive high-frequency horizontal gene transfer (HGT). Here, we demonstrate that the Rhodobacter capsulatus GTA (RcGTA) tailspike protein, TspA, is a potent biofilm-degrading enzyme. Purified TspA is effective at both preventing initial biofilm formation and clearing established, mature biofilms. Crucially, TspA enhances RcGTA-mediated gene transfer, suggesting that this enzyme facilitates GTA navigation through the extracellular matrix. Unlike the permanently anchored tailspikes of canonical phages, TspA possesses a unique {beta}-sandwich N-terminal domain that enables its dissociation from mature particles and engages in biofilm polysaccharide recognition. Our findings indicate that TspA is an evolutionary adaptation used by GTAs to optimize HGT within complex, densely packed microbial biofilm communities.

biochemistry↗

Taming the reference genome jungle: the refget sequence collection standard

Reference genomes are foundational to genomics but suffer from widespread ambiguity and incompatibility due to inconsistent naming, undocumented differences, and lack of formal mechanisms for comparison. To address this, we introduce the GA4GH refget Sequence Collections (seqcol) standard. Refget seqcol is a framework for unambiguous representation, retrieval, and comparison of sequence collections such as reference genomes and transcriptomes. The seqcol standard comprises four components: a structured data schema, a canonical encoding algorithm that produces content-based, globally unique identifiers, a retrieval API, and a comparison protocol. This standard enables precise identification of sequence collections, even across decentralized or private systems, and allows compatibility assessments beyond exact identity, such as order-relaxed matches or shared coordinate systems. We applied the refget seqcol standard to 60 human and 36 mouse reference genomes sourced from major providers. Using digest-based comparisons, we quantified levels of similarity across attributes including sequence names, lengths, coordinate systems, and actual sequence content. Our analysis revealed some consistent subsets of sequences or coordinate systems, as well as substantial incompatibility among references and duplicate references under different names. To support adoption of refget seqcol, we provide a Python package implementing the full standard, a web API, and a comparison interface allowing users to assess local references against a curated database. This work offers a scalable, reproducible solution to the reference genome compatibility crisis, enabling improved transparency, reuse, and integration in genomic analyses. Refget seqcol enhances interoperability across tools and datasets, making genomic research more robust and reproducible.

genomics↗

Cryo-EM resolves the structure of the archaeal dsDNA virus HFTV1 from head to tail

Outnumbering their hosts by at least a factor of 10, viruses are the most common biological entity on Earth, are major drivers of evolution, and greatly impact on the dynamics of our planets ecosystems. While viruses infecting bacteria and eukaryotes have been extensively studied, the viruses roaming the archaeal domain remain largely unexplored. In recent years, a growing number of archaeal viruses have been described, revealing a stunningly diverse range of morphologies that appear unique to archaea. Detailed structural studies are paramount to fully understand how archaeal viruses infect their hosts. However, no complete atomic models of archaeal viruses are available to date. Using electron cryo-microscopy, we investigated the structure of the archaeal virus Haloferax tailed virus 1 (HFTV1), which infects the halophile Haloferax gibbonsii LR2-5 originating from the Senegalese salt lake Retba. Through single particle analysis, we achieved near-atomic resolution for the entire set of HFTV1s structural proteins, enabling the building of a full atomic model of the virion. Comparing the structures of DNA filled and empty capsids, we visualise structural changes occurring upon DNA ejection. By investigating the double-stranded DNA inside the capsid, we elucidate how the genome is spooled upon loading. Furthermore, our structure reveals putative cell-surface receptor-binding and catalytic roles of capsid turret, baseplate, and tail fibre proteins. Together, our data provide new insights into the mechanisms of HFTV1 assembly and infection, unveiling new perspectives on general rules of host-virus interactions in archaea and their evolutionary links to bacterial and eukaryotic viruses.

microbiology↗

Refget: standardised access to reference sequences

Reference sequences are essential in creating a baseline of knowledge for many common bioinformatics methods, especially those using genomic sequencing. We have created refget, a Global Alliance for Genomics and Health API specification to access reference sequences and sub-sequences using an identifier derived from the sequence itself. We present four reference implementations across in-house and cloud infrastructure, a compliance suite and a web report used to ensure specification conformity across implementations. https://w3id.org/ga4gh/refget.

bioinformatics↗

HTSlib - C library for reading/writing high-throughput sequencing data

AbstractO_ST_ABSBackgroundC_ST_ABSSince the original publication of the VCF and SAM formats, an explosion of software tools have been created to process these data files. To facilitate this a library was produced out of the original SAMtools implementation, with a focus on performance and robustness. The file formats themselves have become international standards under the jurisdiction of the Global Alliance for Genomics and Health. FindingsWe present a software library for providing programmatic access to sequencing alignment and variant formats. It was born out of the widely used SAMtools and BCFtools applications. Considerable improvements have been made to the original code plus many new features including newer access protocols, the addition of the CRAM file format, better indexing and iterators, and better use of threading. ConclusionSince the original Samtools release, performance has been considerably improved, with a BAM read-write loop running 5 times faster and BAM to SAM conversion 13 times faster (both using 16 threads, compared to Samtools 0.1.19). Widespread adoption has seen HTSlib downloaded over a million times from GitHub and conda. The C library has been used directly by an estimated 900 GitHub projects and has been incorporated into Perl, Python, Rust and R, significantly expanding the number of uses via other languages. HTSlib is open source and is freely available from htslib.org under MIT / BSD license. Contactsamtools@sanger.ac.uk

bioinformatics↗

Germination ecology of wild and domesticated Ensete ventricosum: Evidence for maintenance of sexual reproductive capacity in a vegetatively propagated perennial crop

O_LILoss of sexual reproductive capacity has been proposed as a syndrome of domestication in vegetatively propagated crops, but there are relatively few examples from agricultural systems. In this study we compare sexual reproductive capacity in wild (sexual) and domesticated (vegetative) populations of enset (Ensete ventricosum (Welw.) Cheesman), a tropical banana relative and Ethiopian food security crop. C_LIO_LIWe examined floral and seed morphology and germination ecology across 35 wild and domesticated enset. We surveyed variation in floral and seed traits, including seed weight, viability and internal morphology, and germinated seeds across a range of constant and alternating temperature regimes to characterise optimum germination requirements. C_LIO_LIWe report highly consistent floral allometry, seed viability, internal morphology and days to germination in wild and domesticated enset. However, seeds from domesticated plants responded to cooler temperatures with greater diurnal range. Shifts in germination behaviour appear concordant with a climatic envelope shift in the domesticated distribution. C_LIO_LIOur findings provide evidence that sexual reproductive capacity has been maintained despite long-term near-exclusive vegetative propagation in domesticated enset. Furthermore, certain traits such as germination behaviour and floral morphology, may be under continued selection, presumably through rare sexually reproductive events. Compared to sexually propagated crops banked as seeds, vegetative crop diversity is typically conserved in living collections that are more costly and insecure. Improved understanding of sexual propagation in vegetative crops may have applications in germplasm conservation and plant breeding. C_LI

ecology↗