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Sternberg, P. W.

Publications and source records attributed to Sternberg, P. W..

At least 19 recordsLinked to original sources

A chromosome-level genome assembly of the classical model nematode Panagrellus redivivus for comparative studies of parasitism evolution

Panagrellus redivivus is a free-living nematode that served as an early model system for nematode biology prior to Caenorhabditis elegans. As a member of Clade IV, a clade harboring major plant-parasitic (e.g., Bursaphelenchus xylophilus) and animal-parasitic (e.g., Strongyloides spp.) species, P. redivivus represents a crucial, phylogenetically proximate non-parasitic reference for investigating the evolution of parasitism. Here, we present a chromosome-level genome assembly of P. redivivus constructed using Oxford Nanopore long reads, Illumina short reads, and Hi-C scaffolding. The assembly is resolved into five chromosome-scale scaffolds, with completeness validated by Hi-C contact maps and the identification of a non-canonical telomeric repeat motif. The assembly demonstrates high gene-space completeness (97.1% BUSCO) and contains 17,839 predicted protein-coding genes. Comparative orthology analysis revealed extensive orthogroup sharing between P. redivivus and Clade IV parasites, enabling comparative evolutionary studies with reduced confounding effects from deep lineage divergence. This high-quality genome provides a key resource for investigating the genetic basis of distinctive biological traits, including ovoviviparity, as well as gene family dynamics and parasite evolution.

genomics↗

Identification of srh-30 as a 2-nonanone receptor in C. elegans

C. elegans detects food, mates, and danger through a large repertoire of chemosensory receptors. The volatile odorant 2-nonanone is a well-established aversive stimulus that reliably elicits avoidance chemotaxis. However, the receptor(s) responsible for its detection have not been identified. Here, we leveraged CeNGEN single-cell expression profiles to identify candidate receptors required for sensing 2-nonanone. We narrowed the list of candidate chemoreceptor genes by selecting genes expressed in the aversive amphid neurons AWB and ASH while excluding genes expressed in other amphid sensory neurons. We tested available mutants from the C. elegans Genetics Center (CGC) and identified srh-30 as a candidate required for normal 2-nonanone avoidance. Two independent srh-30 null alleles generated using CRISPR-Cas9 confirmed that loss of srh-30 causes a partial defect in 2-nonanone sensing. srh-30 promoter-driven fluorescent reporter, mKate, localized to the distal tips of AWB sensory cilia, consistent with a direct sensory role. Finally, ectopic expression of srh-30 in the attractive AWA neuron shifted the behavioral response to 2-nonanone toward neutrality, supporting srh-30 as a sensory receptor. Together, these results identify srh-30 as a sensory receptor mediating 2-nonanone-evoked avoidance and demonstrate a transcriptome-guided strategy for mapping odor receptors.

neuroscience↗

scFAIR Consortium: a decentralized hub for single-cell RNA-Seq data standardization and unification

The rapid accumulation of single-cell RNA-Seq (scRNA-seq) data across multiple repositories presents major challenges for data accessibility, integration, and reproducibility. While primary repositories provide raw data, they rarely include structured cell-type annotations or descriptions of analytical workflows, limiting the ability to reuse and integrate datasets in a FAIR (Findable, Accessible, Interoperable, Reusable) manner. Here we present scFAIR, a consortium of single-cell data resources that has developed a unified metadata schema and common curation framework to improve the FAIRness of scRNA-seq data. Building on and extending the CZ CELLxGENE Discover metadata schema, the scFAIR consortium has been instrumental in driving key schema improvements, including the expansion of supported organisms, richer biological context, and structured reporting of computational workflows. To provide unified access to decentralized datasets, the consortium developed the sc-fair.org portal, which currently aggregates 2,346 datasets across partner resources through ontology-aware semantic search. We demonstrate the practical value of FAIR-compliant datasets through a cross-species validation between human and mouse Allen Brain Atlases, showing that standardized ontology annotations enable reliable annotation transfer across species, with 90% of neuronal clusters receiving an exact or equivalent label. Together, the scFAIR schema, validator, and portal constitute a community-driven framework that advances single-cell data standardization and lays the foundation for reproducible, large-scale integration of single-cell datasets.

bioinformatics↗

Whole-organism spatial transcriptomics at single-cell resolution in C. elegans

Spatial transcriptomics has advanced our understanding of tissue organization by mapping gene expression in its native context yet applying these techniques to whole organisms remains a significant challenge. Caenorhabditis elegans is well-suited to whole organism-level analysis because its compact size, transparency, reproducible anatomy, and genetic tractability make it possible to link molecular and cellular changes to circuit function and behavior within the same animal. However, current transcriptomic approaches in C. elegans are often limited by spatial resolution or multiplexing capacity, making it challenging to profile multiple gene expression patterns across intact worms while preserving spatial context. Here, we present a single-molecule fluorescence in situ hybridization workflow that enables multiplex imaging with single-cell resolution across the entire worm. This approach allows sequential imaging of one gene per fluorescent channel using two channels across 20 hybridization rounds, enabling the profiling of up to 40 genes while preserving spatial context. We further provide a curated marker-gene panel for reproducible neuron identification, which, together with probabilistic assignment of transcripts to segmented nuclei, enables quantitative measurements of gene expression levels. We used this method to identify up to 86 neuronal classes and reveal sex- and neuron-specific expression patterns at single-cell resolution. Together, these results establish a scalable framework for the spatial analysis of gene expression and cell identity in intact C. elegans.

neuroscience↗

k-spaces: Mixtures of Gaussian latent variable models

Principal component analysis (PCA) and k-means clustering are two seemingly different methods for dimension reduction and clustering, respectively, but can be understood as special cases of inference in a Gaussian latent variable model framework. We leverage this insight to develop a probabilistic framework and methods for simultaneous dimension reduction, clustering, and latent space learning that are efficient and interpretable, and that can replace current ad hoc combinations of PCA and clustering. The algorithm, k-spaces, has broad applicability, which we demonstrate in several distinct genomic settings. In particular, we show how k-spaces can be used to model gene expression in quantitative hybridization chain reaction (qHCR) images, for inference in epigenomics, and for dimension reduction of single-cell RNA-sequencing data.

bioinformatics↗

Synaptic MEMOIR: mapping individual synapses of neurons with protein barcodes

Obtaining wiring diagrams of brains has been a major achievement for neuroscience. However, an underlying challenge in connectomics is the fundamental tradeoff between the imaging resolution needed to resolve synapses and the volume of the brain that can be imaged. For example, electron microscopy (EM) visualizes synaptic sites with ~5 nm resolution, but is difficult to scale beyond volumes of 1 mm3. Here, we present Synaptic MEMOIR (Memory with Engineered Mutagenesis with Optical in situ Readout) that enables imaging of neuronal projections in animal brains with single-synapse resolution. Synaptic MEMOIR is built around three key design features. First, protein barcodes are transported to synapses to allow matching of synaptic barcodes to cell body barcodes without high resolution imaging and the error-prone process of tracing neuronal processes across long distances. Second, Synaptic MEMOIR uses continuous mutagenesis to generate a large diversity of barcodes to uniquely label cell bodies and synapses. Last, the timing of recombination and transport can be tuned to record synaptic age or projection information. Combining these features, we demonstrated projection mapping of 113 neurons in the Drosophila melanogaster optic lobe in a volume of 9.5 million m3. Because synapses are identified by transported barcodes with optical microscopy at 300 nm resolution, this approach can potentially scale to much larger volumes, similar at least to those imaged in recent mouse brain transcriptomics atlases. In addition, synaptic MEMOIR can match barcodes across brain sections, and does not require tissue clearing to track long-range projections. Together, these results provide the foundation for a scalable optical image-based system for reconstructing the neural wiring diagrams of brains across different developmental stages, genetic backgrounds and perturbations. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=46 SRC="FIGDIR/small/690442v1_ufig1.gif" ALT="Figure 1"> View larger version (14K): org.highwire.dtl.DTLVardef@8363cdorg.highwire.dtl.DTLVardef@d3240org.highwire.dtl.DTLVardef@5e2793org.highwire.dtl.DTLVardef@1784f2a_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Evolution of parasitism-related traits in nematodes

The abundant resources provided by the host provide an evolutionary rationale for parasitism and drive the metabolic and developmental divergence of parasitic and free-living animals. Two evolutionarily distant nematode genera, Steinernema and Heterorhabditis, independently evolved an entomopathogenic lifestyle, in which they invade insects and kill them with the assistance of specifically associated symbiotic pathogenic bacteria. It had been generally assumed that the worms, being bacterivores, feed on their symbiotic bacteria, which rapidly reproduce as they consume the insect host. The evolutionary adaptations of entomopathogenic nematodes to a parasitic lifestyle developmentally, and the symbiotic relationships of entomopathogenicity, remain largely unknown. We developed an axenic culture medium that supports robust and sustained growth of Steinernema hermaphroditum, with finite control of nutrients available to the nematodes. We found that, uniquely among the nematodes tested, S. hermaphroditum hatchlings cannot endure in a nutrient-poor environment; this ability is impaired but still present in Heterorhabditis bacteriophora. Similarly, the ability to forage for food is completely lost in H. bacteriophora hatchlings and severely compromised in S. hermaphroditum. We reasoned that these traits were lost because they are unnecessary to obligate parasites that always hatch in a resource-rich host. We further found that Steinernema and, to a limited extent, Heterorhabditis nematodes can successfully invade, develop, and reproduce inside a living insect host independent of their symbiotic bacteria, apparently feeding on the hemolymph, and emerge carrying bacteria found within, explaining the evolutionary origins of entomopathogenic nematodes. HighlightsO_LIA simple but robust axenic culturing method for the emerging model nematode Steinernema hermaphroditum and other nematode parasites of invertebrates. C_LIO_LINematode adaptation to parasitism is associated with changes in modes of feeding. C_LIO_LIConvergent evolution led to the loss of hatchling survival traits in entomopathogenic nematodes. C_LIO_LIEntomopathogenic nematodes evolved from parasitoid ancestors and likely acquired their bacterial symbionts from their hosts. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=146 HEIGHT=200 SRC="FIGDIR/small/678730v2_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@880785org.highwire.dtl.DTLVardef@a5cbcforg.highwire.dtl.DTLVardef@e78671org.highwire.dtl.DTLVardef@2b9d99_HPS_FORMAT_FIGEXP M_FIG C_FIG

evolutionary biology↗

Cyclohexyl acetate functions like a volatile sex pheromone mimic in Caenorhabditis nematodes

Nematodes communicate via diverse sex pheromones, including long-range volatile signals, short-range chemical cues, and contact-dependent molecules. While the ascaroside family of small molecules that mediate short-range attraction is well characterized, the identities and roles of volatile sex pheromones (VSPs) that act over longer ranges remain unknown. Using GC-MS analysis of crude VSP extracts, we identified cyclohexyl acetate (CA) as a candidate mimic, sharing retention time and mass spectral features with natural VSPs. Behavioral assays demonstrated that CA acts as a concentration-dependent, male-specific attractant in Caenorhabditis. Pre-exposure to VSPs induced cross-adaptation to CA, suggesting shared sensory processing. Surprisingly, genetic and calcium imaging analyses revealed that CA perception is mediated primarily by AWCon (str-2-expressing) neurons and involves VSPs chemoreceptor srd-1-independent pathways, which are distinct from the neural pathways involved in natural VSPs perception. These findings establish that CA is not a major component of VSPs but a structural and functional mimic of nematode VSPs, operating through a parallel sensory circuit. Although the endogenous source of CA remains unknown, its structural and behavioral mimicry provides new insights into the complexity of chemosensory signaling and the potential for interspecies chemical eavesdropping in nematode ecology.

biochemistry↗

A male-derived volatile sex pheromone in nematodes identified through its mimicry by a predator

Recent studies demonstrated that the predacious fungi Arthrobotrys oligospora emits a mixture of volatile chemical cues that function to attract nematode prey. The strong attraction elicited by one of the mixture components, methyl 3-methyl-2-butenoate (MMB), was highly female- and hermaphrodite-specific within several Caenorhabditis species, including C. remanei and C. elegans, suggesting that MMB might function as a mimic of an endogenous, male-produced, volatile sex pheromone (VSP) within these species. Here, we report evidence that MMB is produced by C. remanei males at levels that are attractive to C. remanei females and C. elegans hermaphrodites. Notably, MMB production was not detected for C. elegans males; a finding which correlates with behavioral assays for which worm-conditioned media (WCM) prepared from C. remanei, but not from C. elegans adult males is strongly attractive to both C. remanei females and C. elegans hermaphrodites. Our findings establish MMB as the first chemically identified VSP in nematodes and show that A. oligospora exploits a dual strategy of chemical deception--mimicry and eavesdropping--to enhance prey capture.

animal behavior and cognition↗

O-Acyltransferase Genes Involved in the Production of Volatile Sex Pheromones in Caenorhabditis elegans

Gene family expansions are critical for functional diversification, yet paralog contributions to metabolic pathways are often unclear. In Caenorhabditis, the expanded O-acyltransferase (OAC) family--enzymes that transfer acyl groups to hydroxylated substrates--remains poorly characterized despite having been implicated in lipid metabolism. Using CRISPR-Cas9 mutagenesis, behavioral assays, gas chromatographic-mass spectral (GC-MS) analyses, and metabolomics, we systematically analyzed 59 OAC-family protein-coding genes to define their roles in regulating signaling molecules. We found that four adjacent paralogs (oac-13, oac-16, oac-25, and oac-28) on chromosome I are required for synthesizing volatile sex pheromones (VSPs)--airborne signals critical for male mate-searching. Specifically, oac-13 and oac-16 are necessary for producing both major pheromone components, while the identical tandem paralogs oac-25 and oac-28 regulate the production of the later-eluting component in gas chromatography. Disruption of these genes reduced production of key pheromone components and impaired male attraction. Metabolomics revealed that oac-16 and other OACs also modulate synthesis and secretion of non-volatile ascaroside pheromones, indicating dual roles in chemical signaling. This work uncovers functional specialization within an expanded gene family, illustrating how redundancy and divergence enable adaptive evolution of communication systems.

biochemistry↗

The forkhead transcription factor FKH-7/FOXP acts in chemosensory neurons to regulate developmental decision-making

Autism is a complex neurodevelopmental disorder with many associated genetic factors, including the forkhead transcription factor FOXP1. Although FOXP1s neuronal role is well-studied, the specific molecular consequences of different FOXP1 pathogenic variants in physiologically-relevant contexts are unknown. Here we ascribe the first function to Caenorhabditis elegans FKH-7/FOXP, which acts in two chemosensory neuron classes to promote the larval decision to enter the alternative, developmentally-arrested dauer life stage. We demonstrate that human FOXP1 can functionally substitute for C. elegans FKH-7 in these neurons and that engineering analogous FOXP1 hypomorphic missense mutations in the endogenous fkh-7 locus also impairs developmental decision-making. In a fkh-7/FOXP1 missense variant, single-cell transcriptomics identifies downregulated expression of autism-associated kcnl-2/KCNN2 calcium-activated potassium channel in a serotonergic sensory neuron. Our findings establish a novel framework linking two evolutionarily-conserved autism-associated genes for deeper characterization of variant-specific molecular pathology at single neuron resolution in the context of a developmental decision-making paradigm.

neuroscience↗

Genomes of the entomopathogenic nematode Steinernema hermaphroditum and its associated bacteria

As an entomopathogenic nematode (EPN), Steinernema hermaphroditum parasitizes insect hosts and harbors symbiotic Xenorhabdus griffinae bacteria. In contrast to other Steinernematids, S. hermaphroditum has hermaphroditic genetics, offering the experimental scope found in Caenorhabditis elegans. To enable biological analysis of S. hermaphroditum, we have assembled and analyzed its reference genome. This genome assembly has five chromosomal scaffolds and 83 unassigned scaffolds totaling 90.7 Mb, with 19,426 protein-coding genes having a BUSCO completeness of 88.0%. Its autosomes show higher densities of strongly conserved genes in their centers, as in C. elegans, but repetitive elements are evenly distributed along all chromosomes, rather than with higher arm densities as in C. elegans. Either when comparing protein motif frequencies between nematode species or when analyzing gene family expansions during nematode evolution, we observed two categories of genes preferentially associated with the origin of Steinernema or S. hermaphroditum: orthologs of venom genes in S. carpocapsae or S. feltiae; and some types of chemosensory G protein-coupled receptors, despite the tendency of parasitic nematodes to have reduced numbers of chemosensory genes. Three-quarters of venom orthologs occurred in gene clusters, with the larger clusters comprising functionally diverse pathogenicity islands rather than paralogous repeats of a single venom gene. While assembling the genome of S. hermaphroditum, we coassembled bacterial genomes, finding sequence data for not only the known symbiont, X. griffinae, but also for eight other bacterial genera. All eight genera have previously been observed to be associated with Steinernema species or the EPN Heterorhabditis, and may constitute a "second bacterial circle" of EPNs. The genome assemblies of S. hermaphroditum and its associated bacteria will enable use of these organisms as a model system for both entomopathogenicity and symbiosis.

genomics↗

Characterization and automated classification of sentences in the biomedical literature: a case study for biocuration of gene expression and protein kinase activity

Biological knowledgebases are essential resources for biomedical researchers, providing ready access to gene function and genomic data. Professional, manual curation of knowledgebases, however, is labor-intensive and thus high-performing machine learning methods that improve biocuration efficiency are needed. Here we report on sentence-level classification to identify biocuration-relevant sentences in the full text of published references for two gene function data types: gene expression and protein kinase activity. We performed a detailed characterization of sentences from references in the WormBase bibliography and used this characterization to define three tasks for classifying sentences as either 1) fully curatable, 2) fully and partially curatable, or 3) all language-related. We evaluated various machine learning (ML) models applied to these tasks and found that GPT and BioBERT achieve the highest average performance, resulting in F1 performance scores ranging from 0.89 to 0.99 depending upon the task. Our findings demonstrate the feasibility of extracting biocuration-relevant sentences from full text. Integrating these models into professional biocuration workflows, such as those used by the Alliance of Genome Resources and the ACKnowledge community curation platform, might well facilitate efficient and accurate annotation of the biomedical literature.

bioinformatics↗

Efficient pheromone navigation via antagonistic detectors

Chemotaxis to a moving potential mate that emits a volatile sex pheromone poses a navigation challenge requiring rapid, precise responses to maximize reproductive success. Volatile chemicals form gradients that differ from soluble compounds, potentially making navigation based on comparisons between spatially separated sensors unreliable for small-bodied animals. Here we show that, rather than a simple spatial comparison, Caenorhabditis elegans males employ an antagonistic strategy, comparing inputs from sex-shared head (AWA) and male-specific tail (PHD) sensory neurons with distinct response properties. Despite sharing a receptor, SRD-1, these detectors play different roles: AWAs promote forward movement and acceleration, while PHDs induce reversals and deceleration. In rising pheromone gradients, AWA activity dominates; in falling gradients, AWA inactivates, allowing PHD to correct trajectories. AWAs are essential for mate-searching, while PHDs are crucial for complex tasks. A minimal computational model reproduces these behaviors and infers how head-tail signals are combined. Thus, a sexually dimorphic, antagonistic sensory system enables adaptive navigation in dynamic environments

neuroscience↗

Neuronal activity regulating the dauer entry decision in Caenorhabditis elegans

The model nematode Caenorhabditis elegans can choose between two alternative developmental trajectories. Larvae can either become reproductive adults or, under conditions of crowding or low food availability, enter a long-term, stress-resistant diapause known as the dauer stage. Previous studies showed that chemical signals from a secreted larval pheromone promote the dauer trajectory, and that their influence can be antagonised by increased availability of microbial food. The decision is known to be under neuronal control, involving both sensory and interneurons. To make an accurate decision, larvae must collect and compare complex patterns of environmental input over several hours of early larval development. The full composition of this circuit and the algorithm for decision-making are unknown. Here, we used cell-specific chemical silencing to systematically perturb several sensory and interneurons to further elucidate circuit composition. Our results suggest a role for gas-sensing neurons in regulating dauer entry. In addition, we quantitatively characterized the neuronal responses to food and pheromone inputs by measuring calcium traces from ASI and AIA neurons. We found that calcium in ASI increases linearly in response to food, and similarly decreases in response to pheromone, revealing a cellular site of antagonism between these key chemical inputs. Notably, the ASI response persists well beyond removal of the food stimulus, thus encoding a memory of recent food exposure. In contrast, AIA reports instantaneous food availability, and is unaffected by pheromone. We discuss how these findings may inform our understanding of this long-term decision-making process.

neuroscience↗

Sensory integration of food availability and population density during the diapause exit decision involves insulin-like signaling in Caenorhabditis elegans

Decisions made over long time scales, such as life cycle decisions, require coordinated interplay between sensory perception and sustained gene expression. The Caenorhabditis elegans dauer (or diapause) exit developmental decision requires sensory integration of population density and food availability to induce an all-or-nothing organismal-wide response, but the mechanism by which this occurs remains unknown. Here, we demonstrate how the ASJ chemosensory neurons, known to be critical for dauer exit, perform sensory integration at both the levels of gene expression and calcium activity. In response to favorable conditions, dauers rapidly produce and secrete the dauer exit-promoting insulin-like peptide INS-6. Expression of ins-6 in the ASJ neurons integrate population density and food level and can reflect decision commitment since dauers committed to exiting have higher ins-6 expression levels than those of non-committed dauers. Calcium imaging in dauers reveals that the ASJ neurons are activated by food, and this activity is suppressed by pheromone, indicating that sensory integration also occurs at the level of calcium transients. We find that ins-6 expression in the ASJ neurons depends on neuronal activity in the ASJs, cGMP signaling, a CaM-kinase pathway, and the pheromone components ascr#8 and ascr#2. We propose a model in which decision commitment to exit the dauer state involves an autoregulatory feedback loop in the ASJ neurons that promotes high INS-6 production and secretion. These results collectively demonstrate how insulin-like peptide signaling helps animals compute long-term decisions by bridging sensory perception to decision execution. Summary/Significance StatementAnimals must respond appropriately to multiple sensory stimuli to make informed decisions. It remains unclear how the nervous system is able to integrate different sensory cues and propagate that information towards making decisions over longer timescales. We use the nematode Caenorhabditis elegans to investigate how sensory integration occurs during the decision to exit diapause, a stress-resistant developmentally arrested state triggered by multiple sensory inputs including food availability and population density. We show how expression of an insulin-like peptide critical to dauer exit reflects the sensory integration process and decision commitment, and we dissect the regulation of this insulin-like peptides expression. Our study explicitly analyzes the relationship between neuronal activity and neuropeptide expression during a complex decision with diverse sensory inputs.

neuroscience↗

Single tissue proteomics in Caenorhabditis elegans reveals proteins resident in intestinal lysosome-related organelles

The nematode intestine is the primary site for nutrient uptake and storage as well as the synthesis of biomolecules; lysosome-related organelles known as gut granules are important for many of these functions. Aspects of intestine biology are not well understood, including the export of the nutrients it imports and the molecules it synthesizes, as well as the complete functions and protein content of the gut granules. Here, we report a mass spectrometry-based proteomic analysis of the intestine of the Caenorhabditis elegans and of its gut granules. Overall, we identified approximately 5,000 proteins each in the intestine and the gonad and showed that most of these proteins can be detected in samples extracted from a single worm, suggesting the feasibility of individual-level genetic analysis using proteomes. Comparing proteomes and published transcriptomes of the intestine and the gonad, we identified proteins that appear to be synthesized in the intestine and then transferred to the gonad. To identify gut granule proteins, we compared the proteome of individual intestines deficient in gut granules to the wild-type. The identified gut granule proteome includes proteins known to be exclusively localized to the granules and additional putative novel gut granule proteins. We selected two of these putative gut granule proteins for validation via immunohistochemistry, and our successful confirmation of both suggests that our strategy was effective in identifying the gut granule proteome. Our results demonstrate the practicability of single tissue mass-spectrometry- based proteomic analysis in small organisms and in its utility for making discoveries. Significance statementWe show that tissue-specific proteomic analysis is achievable and can be done efficiently at an individual level in a small nematode, with resolution sufficient for genetic analysis on a single animal basis. With data collected from single animals, we produced high-quality sets of proteins that described the proteomes of the gonad and the intestine. Comparison of these proteomes with the organs transcriptomes improved our understanding of interorgan protein transport. We applied single-tissue proteomic to describe the proteome of the gut granules in the nematode intestine, a specialized lysosome-related organelle with important functions but which is not well characterized, identifying proteins not previously known to be associated with LROs and verifying two by subcellular localization.

cell biology↗

Updates to the Alliance of Genome Resources Central Infrastructure

The Alliance of Genome Resources (Alliance) is an extensible coalition of knowledgebases focused on the genetics and genomics of intensively-studied model organisms. The Alliance is organized as individual knowledge centers with strong connections to their research communities and a centralized software infrastructure, discussed here. Model organisms currently represented in the Alliance are budding yeast, C. elegans, Drosophila, zebrafish, frog, laboratory mouse, laboratory rat, and the Gene Ontology Consortium. The project is in a rapid development phase to harmonize knowledge, store it, analyze it, and present it to the community through a web portal, direct downloads, and APIs. Here we focus on developments over the last two years. Specifically, we added and enhanced tools for browsing the genome (JBrowse), downloading sequences, mining complex data (AllianceMine), visualizing pathways, full-text searching of the literature (Textpresso), and sequence similarity searching (SequenceServer). We enhanced existing interactive data tables and added an interactive table of paralogs to complement our representation of orthology. To support individual model organism communities, we implemented species-specific "landing pages" and will add disease-specific portals soon; in addition, we support a common community forum implemented in Discourse. We describe our progress towards a central persistent database to support curation, the data modeling that underpins harmonization, and progress towards a state-of-the art literature curation system with integrated Artificial Intelligence and Machine Learning (AI/ML).

bioinformatics↗