WormBase 2024: status and transitioning to Alliance infrastructure.

WormBase has been the major repository and knowledgebase of information about the genome and genetics of Caenorhabditis elegans and other nematodes of experimental interest for over 2 decades. We have 3 goals: to keep current with the fast-paced C. elegans research, to provide better integration with other resources, and to be sustainable. Here, we discuss the current state of WormBase as well as progress and plans for moving core WormBase infrastructure to the Alliance of Genome Resources (the Alliance). As an Alliance member, WormBase will continue to interact with the C. elegans community, develop new features as needed, and curate key information from the literature and large-scale projects.

WormBase in 2022-data, processes, and tools for analyzing Caenorhabditis elegans.

WormBase (www.wormbase.org) is the central repository for the genetics and genomics of the nematode Caenorhabditis elegans. We provide the research community with data and tools to facilitate the use of C. elegans and related nematodes as model organisms for studying human health, development, and many aspects of fundamental biology. Throughout our 22-year history, we have continued to evolve to reflect progress and innovation in the science and technologies involved in the study of C. elegans. We strive to incorporate new data types and richer data sets, and to provide integrated displays and services that avail the knowledge generated by the published nematode genetics literature. Here, we provide a broad overview of the current state of WormBase in terms of data type, curation workflows, analysis, and tools, including exciting new advances for analysis of single-cell data, text mining and visualization, and the new community collaboration forum. Concurrently, we continue the integration and harmonization of infrastructure, processes, and tools with the Alliance of Genome Resources, of which WormBase is a founding member.

Ensembl Genomes 2022: an expanding genome resource for non-vertebrates.

Ensembl Genomes (https://www.ensemblgenomes.org) provides access to non-vertebrate genomes and analysis complementing vertebrate resources developed by the Ensembl project (https://www.ensembl.org). The two resources collectively present genome annotation through a consistent set of interfaces spanning the tree of life presenting genome sequence, annotation, variation, transcriptomic data and comparative analysis. Here, we present our largest increase in plant, metazoan and fungal genomes since the project's inception creating one of the world's most comprehensive genomic resources and describe our efforts to reduce genome redundancy in our Bacteria portal. We detail our new efforts in gene annotation, our emerging support for pangenome analysis, our efforts to accelerate data dissemination through the Ensembl Rapid Release resource and our new AlphaFold visualization. Finally, we present details of our future plans including updates on our integration with Ensembl, and how we plan to improve our support for the microbial research community. Software and data are made available without restriction via our website, online tools platform and programmatic interfaces (available under an Apache 2.0 license). Data updates are synchronised with Ensembl's release cycle.

Accelerating public sector rice breeding with high-density KASP markers derived from whole genome sequencing of indica rice.

Few public sector rice breeders have the capacity to use NGS-derived markers in their breeding programmes despite rapidly expanding repositories of rice genome sequence data. They rely on > 18,000 mapped microsatellites (SSRs) for marker-assisted selection (MAS) using gel analysis. Lack of knowledge about target SNP and InDel variant loci has hampered the uptake by many breeders of Kompetitive allele-specific PCR (KASP), a proprietary technology of LGC genomics that can distinguish alleles at variant loci. KASP is a cost-effective single-step genotyping technology, cheaper than SSRs and more flexible than genotyping by sequencing (GBS) or array-based genotyping when used in selection programmes. Before this study, there were 2015 rice KASP marker loci in the public domain, mainly identified by array-based screening, leaving large proportions of the rice genome with no KASP coverage. Here we have addressed the urgent need for a wide choice of appropriate rice KASP assays and demonstrated that NGS can detect many more KASP to give full genome coverage. Through re-sequencing of nine indica rice breeding lines or released varieties, this study has identified 2.5 million variant sites. Stringent filtering of variants generated 1.3 million potential KASP assay designs, including 92,500 potential functional markers. This strategy delivers a 650-fold increase in potential selectable KASP markers at a density of 3.1 per 1 kb in the indica crosses analysed and 377,178 polymorphic KASP design sites on average per cross. This knowledge is available to breeders and has been utilised to improve the efficiency of public sector breeding in Nepal, enabling identification of polymorphic KASP at any region or quantitative trait loci in relevant crosses. Validation of 39 new KASP was carried out by genotyping progeny from a range of crosses to show that they detected segregating alleles. The new KASP have replaced SSRs to aid trait selection during marker-assisted backcrossing in these crosses, where target traits include rice blast and BLB resistance loci. Furthermore, we provide the software for plant breeders to generate KASP designs from their own datasets.

A genome-wide survey of DNA methylation in hexaploid wheat.

BACKGROUND: DNA methylation is an important mechanism of epigenetic gene expression control that can be passed between generations. Here, we use sodium bisulfite treatment and targeted gene enrichment to study genome-wide methylation across the three sub-genomes of allohexaploid wheat. RESULTS: While the majority of methylation is conserved across all three genomes we demonstrate that differential methylation exists between the sub-genomes in approximately equal proportions. We correlate sub-genome-specific promoter methylation with decreased expression levels and show that altered growing temperature has a small effect on methylation state, identifying a small but functionally relevant set of methylated genes. Finally, we demonstrate long-term methylation maintenance using a comparison between the D sub-genome of hexaploid wheat and its progenitor Aegilops tauschii. CONCLUSIONS: We show that tri-genome methylation is highly conserved with the diploid wheat progenitor while sub-genome-specific methylation shows more variation.

Trade-off of dynamic fragility but not of robustness in metabolic pathways in silico.

Selective robustness is a key feature of biochemical networks. It confers a fitness benefit to organisms living in dynamic environments. The (in-)sensitivity of a network to external perturbations results from the interplay between network dynamics, structure and enzyme kinetics. In this work, we focus on the subtle interplay between robustness and control (fragility). We describe a quantitative method for defining the fragility and robustness of system fluxes to perturbations. We find that for many mathematical models of metabolic pathways, the robustness of fluxes vis-à-vis perturbations of all the enzyme activities is captured by a broad distribution of the robustness coefficients. We find that in cases where a metabolic pathway flux is made less robust with respect to the perturbation of a particular network step, the average robustness may still be increased. We then show that fragility is conserved upon a perturbation of network processes and equate fragility with control as defined in metabolic control analysis. This highlights the non-intuitive nature of the interplay between fragility and robustness and the need for a dynamic network understanding.