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Wood, V.

Publications and source records attributed to Wood, V..

9 recordsLinked to original sources

GOFlowLLM - Curating miRNA literature with Large Language Models and flowcharts

The exponential growth of non-coding RNA research--with over 230,000 papers published since 2000--has created an urgent knowledge management crisis in molecular biology. Despite their crucial regulatory roles, microRNAs (miRNAs) face a significant curation bottleneck, with only 1,400 articles manually curated to the Gene Ontology (GO) knowledgebase over a decade. We present GOFlowLLM, an automated curation pipeline powered by reasoning-enabled Large Language Models (LLMs) that follows established GO curation flowcharts to extract and structure miRNA-mediated gene silencing data at scale. When evaluated on existing curation, GOFlowLLM selects the correct GO term in 90% of cases. Curators also agree with 95% of the systems reasoning steps and 90% of the evidence selected. Applied to 6,996 previously uncurated articles, our system identified 2,538 new candidate GO annotations on 1,785 articles in just 58 hours--potentially doubling the available miRNA GO curation. Manual review of a subset of these annotations shows that curators agreed with the selected term in 87% of cases, the models reasoning in 92% of cases, and the extracted evidence in 93%. GOFlowLLM demonstrates how LLMs can significantly accelerate biocuration while maintaining high-quality standards by following expert-designed reasoning frameworks. The integration of reasoning traces in our system provides transparent justification for annotations that can be reviewed by human curators, addressing one of the key challenges in adopting AI for scientific curation, potentially transforming how we manage the growing corpus of scientific knowledge in molecular biology. GoFlowLLM is available on github: https://github.com/RNAcentral/GO_Flow_LLM.

bioinformatics↗

RNAcentral in 2026: Genes and literature integration

RNAcentral was founded in 2014 to serve as a comprehensive database of non-coding RNA sequences. It began by providing a single unified interface to more specialised resources, and now contains 45 million sequences. It has grown beyond providing a single interface to many specialised resources and now provides several services and analyses. These include secondary structure prediction with R2DT, sequence search, and analysis with Rfam. Since its last publication in 2021, RNAcentral has developed two major features. First, literature integration with the development of LitScan and LitSumm. LitScan automatically identifies and links relevant publications to RNA entries, while LitSumm uses natural language processing to generate functional summaries from the literature. Together, these tools address the critical challenge of connecting sequence data with scattered functional knowledge across thousands of publications. Secondly, RNAcentral has created gene level entries. Gene level entries represent a large structural change to RNAcentral. While RNAcentral previously organized data exclusively at the sequence level, we now group related transcripts into gene-centric views. This allows researchers to explore all isoforms, splice variants, and related sequences for a gene in a unified interface, better reflecting biological organization and facilitating comparative analyses. RNAcentral is freely available at: https://rnacentral.org.

bioinformatics↗

A framework for community curation of interspecies interactions literature

The quantity and complexity of data being generated and published in biology has increased substantially, but few methods exist for capturing knowledge about phenotypes derived from molecular interactions between diverse groups of species, in such a way that is amenable to data-driven biology and research. To improve access to this knowledge, we have constructed a framework for the curation of the scientific literature studying interspecies interactions, using data curated for the Pathogen-Host Interactions Database (PHI-base) as a case study. The framework provides a curation tool, phenotype ontology and controlled vocabularies to curate pathogen-host interaction data (at the level of the host, pathogen, strain, gene and genotype). The concept of a multispecies genotype, the metagenotype, is introduced to facilitate capturing changes in the pathogens disease-causing abilities, and host resistance or susceptibility observed by gene alterations. We report on this framework and describe PHI-Canto, a community curation tool for use by publication authors.

microbiology↗

Reciprocal Best Structure Hits: Using AlphaFold models to discover distant homologues

1The conventional methods to detect homologous protein pairs use the comparison of protein sequences. But the sequences of two homologous proteins may diverge significantly and consequently may be undetectable by standard approaches. The release of the AlphaFold 2.0 software enables the prediction of highly accurate protein structures and opens many opportunities to advance our understanding of protein functions, including the detection of homologous protein structure pairs. In this proof-of-concept work, we search for the closest homologous protein pairs using the structure models of five model organisms from the AlphaFold database. We compare the results with homologous protein pairs detected by their sequence similarity and show that the structural matching approach finds a similar set of results. Additionally, we detect potential novel homologues solely with the structural matching approach, which can help to understand the function of uncharacterised proteins and make previously overlooked connections between well-characterised proteins. We also observe limitations of our implementation of the structure based approach, particularly when handling highly disordered proteins or short protein structures. Our work shows that high accuracy protein structure models can be used to discover homologous protein pairs, and we expose areas for improvement of this structural matching approach.

bioinformatics↗

JaponicusDB: Rapid deployment of a model organism database for an emerging model species

The fission yeast Schizosaccharomyces japonicus has recently emerged as a powerful system for studying the evolution of essential cellular processes, drawing on similarities as well as key differences between S. japonicus and the related, well-established model Schizosaccharomyces pombe. We have deployed the open-source, modular code and tools originally developed for PomBase, the S. pombe model organism database (MOD), to create JaponicusDB (www.japonicusdb.org), a new MOD dedicated to S. japonicus. By providing a central resource with ready access to a growing body of experimental data, ontology-based curation, seamless browsing and querying, and the ability to integrate new data with existing knowledge, JaponicusDB supports fission yeast biologists to a far greater extent than any other source of S. japonicus data. JaponicusDB thus enables S. japonicus researchers to realise the full potential of studying a newly emerging model species, and illustrates the widely applicable power and utility of harnessing reusable PomBase code to build a comprehensive, community-maintainable repository of species-relevant knowledge.

bioinformatics↗

Fission stories: Using PomBase to understand Schizosaccharomyces pombe biology

PomBase (www.pombase.org), the model organism database (MOD) for the fission yeast Schizosaccharomyces pombe, supports research within and beyond the S. pombe community by integrating and presenting genetic, molecular, and cell biological knowledge into intuitive displays and comprehensive data collections. With new content, novel query capabilities, and biologist-friendly data summaries and visualisation, PomBase also drives innovation in the MOD community.

bioinformatics↗

Term Matrix: A novel Gene Ontology annotation quality control system based on ontology term co-annotation patterns

Biological processes are accomplished by the coordinated action of gene products. Gene products often participate in multiple processes, and can therefore be annotated to multiple Gene Ontology (GO) terms. Nevertheless, processes that are functionally, temporally, and/or spatially distant may have few gene products in common, and co-annotation to unrelated processes likely reflects errors in literature curation, ontology structure, or automated annotation pipelines. We have developed an annotation quality control workflow that uses rules based on mutually exclusive processes to detect annotation errors, based on and validated by case studies including the three we present here: fission yeast protein-coding gene annotations over time; annotations for cohesin complex subunits in human and model species; and annotations using a selected set of GO biological process terms in human and five model species. For each case study, we reviewed available GO annotations, identified pairs of biological processes which are unlikely to be correctly co-annotated to the same gene products (e.g., amino acid metabolism and cytokinesis), and traced erroneous annotations to their sources. To date we have generated 107 quality control rules, and corrected 289 manual annotations in eukaryotes and over 2.5 million automatically propagated annotations across all taxa.

bioinformatics↗

Hidden in plain sight: What remains to be discovered in the eukaryotic proteome?

The first decade of genome sequencing stimulated an explosion in the characterization of unknown proteins. More recently, the pace of functional discovery has slowed, leaving around 20% of the proteins even in well-studied model organisms without informative descriptions of their biological roles. Remarkably, many uncharacterized proteins are conserved from yeasts to human, suggesting that they contribute to fundamental biological processes. To fully understand biological systems in health and disease, we need to account for every part of the system. Unstudied proteins thus represent a collective blind spot that limits the progress of both basic and applied biosciences.\n\nWe use a simple yet powerful metric based on Gene Ontology (GO) biological process terms to define characterized and uncharacterized proteins for human, budding yeast, and fission yeast. We then identify a set of conserved but unstudied proteins in S. pombe, and classify them based on a combination of orthogonal attributes determined by large-scale experimental and comparative methods. Finally, we explore possible reasons why these proteins remain neglected, and propose courses of action to raise their profile and thereby reap the benefits of completing the catalog of proteins biological roles.

molecular biology↗

Organisation of the transcriptional regulation of genes involved in protein transactions in yeast

The topological analyses of many large-scale molecular interaction networks often provide only limited insights into network function or evolution. In this paper, we argue that the functional heterogeneity of network components, rather than network size, is the main factor limiting the utility of topological analysis of large cellular networks. We have analysed large epistatic, functional, and transcriptional regulatory networks of genes that were attributed to the following biological process groupings: protein transactions, gene expression, cell cycle, and small molecule metabolism. Control analyses were performed on networks of randomly selected genes. We identified novel biological features emerging from the analysis of functionally homogenous biological networks irrespective of their size. In particular, direct regulation by transcription as an underrepresented feature of protein transactions. The analysis also demonstrated that the regulation of the genes involved in protein transactions at the transcriptional level was orchestrated by only a small number of regulators. Quantitative proteomic analysis of nuclear- and chromatin-enriched sub-cellular fractions of yeast provided supportive evidence for the conclusions generated by network analyses.

systems biology↗