PubChem 2025 update

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 53(D1), P. D1516 - D1525

Published: Nov. 18, 2024

Abstract PubChem (https://pubchem.ncbi.nlm.nih.gov) is a large and highly-integrated public chemical database resource at NIH. In the past two years, significant updates were made to PubChem. With additions from over 130 new sources, contains >1000 data 119 million compounds, 322 substances 295 bioactivities. New interfaces, such as consolidated literature panel patent knowledge panel, developed. The combines all references about compound into single list, allowing users easily find, sort, export relevant articles for in one place. panels given query or gene display chemicals, genes, diseases co-mentioned with documents, helping explore relationships between co-occurring entities within documents. PubChemRDF was expanded include co-occurrence underlying enabling exploit semantic web technologies entity based on co-occurrences scientific literature. usability accessibility of information chemicals non-discrete structures (e.g. biologics, minerals, polymers, UVCBs glycans) greatly improved dedicated pages that provide comprehensive view available these chemicals.

Language: Английский

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Updates to the Alliance of Genome Resources central infrastructure

Genetics, Journal Year: 2024, Volume and Issue: 227(1)

Published: March 29, 2024

Abstract The Alliance of Genome Resources (Alliance) is an extensible coalition knowledgebases focused on the genetics and genomics intensively studied model organisms. organized as individual knowledge centers with strong connections to their research communities a centralized software infrastructure, discussed here. Model organisms currently represented in are budding yeast, Caenorhabditis elegans, Drosophila, zebrafish, frog, laboratory mouse, rat, Gene Ontology Consortium. project rapid development phase harmonize knowledge, store it, analyze present it community through web portal, direct downloads, application programming interfaces (APIs). Here, we focus developments over last 2 years. Specifically, added enhanced tools for browsing genome (JBrowse), downloading sequences, mining complex data (AllianceMine), visualizing pathways, full-text searching literature (Textpresso), sequence similarity (SequenceServer). We existing interactive tables table paralogs complement our representation orthology. To support organism communities, implemented species-specific “landing pages” will add disease-specific portals soon; addition, common forum Discourse software. describe progress toward central persistent database curation, modeling that underpins harmonization, state-of-the-art curation system integrated artificial intelligence machine learning (AI/ML).

Language: Английский

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The Caenorhabditis elegans cuticle and precuticle: a model for studying dynamic apical extracellular matrices in vivo

Genetics, Journal Year: 2024, Volume and Issue: 227(4)

Published: July 12, 2024

Apical extracellular matrices (aECMs) coat the exposed surfaces of animal bodies to shape tissues, influence social interactions, and protect against pathogens other environmental challenges. In nematode Caenorhabditis elegans, collagenous cuticle zona pellucida protein-rich precuticle aECMs alternately external epithelia across molt cycle play many important roles in worm's development, behavior, physiology. Both these types contain matrix proteins related those vertebrates, as well some that are nematode-specific. Extensive differences observed among tissues life stages demonstrate a major feature epithelial cell identity. addition forming discrete layers, components assemble into complex substructures such ridges, furrows, nanoscale pillars. The epidermis mechanically linked, allowing sense damage induce protective innate immune stress responses. C. elegans model, with its optical transparency, facilitates study aECM biology structure/function relationships all myriad ways by which can an organism.

Language: Английский

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NCBI RefSeq: reference sequence standards through 25 years of curation and annotation

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 53(D1), P. D243 - D257

Published: Nov. 11, 2024

Reference sequences and annotations serve as the foundation for many lines of research today, from organism sequence identification to providing a core description genes, transcripts proteins found in an organism's genome. Interpretation data including transcriptomics, proteomics, variation comparative analyses based on reference gene informs our understanding function possible disease mechanisms, leading new biomedical discoveries. The Sequence (RefSeq) resource created at National Center Biotechnology Information (NCBI) leverages both automatic processes expert curation create robust set genomic, transcript protein spanning tree life. RefSeq continues refine its annotation quality control utilize better genomes resulting advances sequencing technologies well RNA-Seq produce high-quality annotated genomes, ortholog predictions across more organisms other products that are easily accessible through multiple NCBI resources. This report summarizes current status eukaryotic, prokaryotic viral resources, with focus eukaryotic annotation, increase taxonomic representation effect it will have genomics. is publicly https://www.ncbi.nlm.nih.gov/refseq.

Language: Английский

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Naturally occurring variation in a cytochrome P450 modifies thiabendazole responses independently of beta-tubulin

PLoS Pathogens, Journal Year: 2025, Volume and Issue: 21(1), P. e1012602 - e1012602

Published: Jan. 14, 2025

Widespread anthelmintic resistance has complicated the management of parasitic nematodes. Resistance to benzimidazole (BZ) drug class is nearly ubiquitous in many species and associated with mutations beta-tubulin genes. However, alone do not fully explain all BZ resistance. We performed a genome-wide association study using genetically diverse panel Caenorhabditis elegans strains identify loci that contribute thiabendazole (TBZ). identified quantitative trait locus (QTL) on chromosome V independent genes overlapping two promising candidate genes, cytochrome P450 gene cyp-35D1 nuclear hormone receptor nhr-176 . Both were previously demonstrated play role TBZ metabolism. NHR-176 binds induces expression CYP-35D1, which metabolizes TBZ. generated single deletions found both response. A predicted high-impact lysine-to-glutamate substitution at position 267 (K267E) CYP-35D1 was sensitive strain, reciprocal allele replacement different genetic backgrounds used show lysine conferred increased Using competitive fitness assays, we neither deleterious, but selected presence Additionally, significantly rate metabolism compared glutamate allele. Moreover, yeast assays showed version had twice enzymatic activity To connect our results nematodes, analyzed four Haemonchus contortus orthologs did find variation fenbendazole-resistant populations. Overall, confirmed this first

Language: Английский

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The Nematode Pristionchus pacificus Requires the Gβ and Gγ Proteins for Light Adaptation But Not For Light Avoidance

ZOOLOGICAL SCIENCE, Journal Year: 2025, Volume and Issue: 42(1)

Published: Jan. 29, 2025

Most organisms can sense and adapt to a wide range of light intensities. Although animals commonly use opsins for detection, the nematode Pristionchus pacificus lacks conserved photoreceptors. The cyclic GMP signaling pathway G protein-coupled receptor kinase are essential light-avoidance behavior in P. pacificus. mechanism sensing has been partially elucidated, it remains unclear whether, how, adapts light. Here, we found that prior exposure reduced frequency pacificus, indicating its ability To reveal adaptation used CRISPR/Cas9 genome editing generate Gβ Gγ subunit mutants, as these subunits involved chemosensory Caenorhabditis elegans. mutants exhibited similar wild type, but was impaired mutants. Similarly, arrestin showed minor abnormalities adaptation. These findings suggest proteins play role sensory beyond chemosensation could contribute response mechanisms nematodes.

Language: Английский

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Caenorhabditis elegans Hedgehog-related proteins are tissue- and substructure-specific components of the cuticle and precuticle

Genetics, Journal Year: 2024, Volume and Issue: 227(4)

Published: May 13, 2024

Abstract In Caenorhabditis elegans, expanded families of divergent Hedgehog-related and patched-related proteins promote numerous processes ranging from epithelial sense organ development to pathogen responses cuticle shedding during the molt cycle. The molecular functions these have been mysterious since nematodes lack a canonical Hedgehog signaling pathway. Here we show that are components precuticle apical extracellular matrices coat, shape, protect external epithelia. Of four imaged, two (GRL-2 GRL-18) stably associated with cuticles specific tubes (GRL-7 WRT-10) labeled substructures such as furrows or alae. We found wrt-10 mutations disrupt alae ridges, consistent structural role in matrix organization. hypothesize most nematode components, model could explain many reported for this family. These results highlight ancient connections between suggest any roles C. elegans will be intimately related their association.

Language: Английский

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NEKL-4 regulates microtubule stability and mitochondrial health in ciliated neurons

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 223(9)

Published: May 20, 2024

Ciliopathies are often caused by defects in the ciliary microtubule core. Glutamylation is abundant cilia, and its dysregulation may contribute to ciliopathies neurodegeneration. Mutation of deglutamylase CCP1 causes infantile-onset In C. elegans, ccpp-1 loss age-related degradation that suppressed a mutation conserved NEK10 homolog nekl-4. NEKL-4 absent from yet it negatively regulates stability via an unknown, glutamylation-independent mechanism. We show was mitochondria-associated. Additionally, nekl-4 mutants had longer mitochondria, higher baseline mitochondrial oxidation state, ccpp-1∆ mutant lifespan extension response oxidative stress. A kinase-dead nekl-4(KD) ectopically localized cilia rescued degenerating doublet B-tubules. nondegradable nekl-4(PEST∆) resembled with dye-filling B-tubule breaks. The Dyf phenotype depolymerizing kinesin-8 KLP-13/KIF19A. conclude influences activating kinesins promoting homeostasis.

Language: Английский

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Chromosome-contiguous genome for the Haecon-5 strain of Haemonchus contortus reveals marked genetic variability and enables the discovery of essential gene candidates

International Journal for Parasitology, Journal Year: 2024, Volume and Issue: 54(13), P. 705 - 715

Published: Aug. 22, 2024

Millions of livestock animals worldwide are infected with the haematophagous barber's pole worm, Haemonchus contortus, aetiological agent haemonchosis. Despite major significance this parasite and its widespread resistance to current treatments, lack a high-quality genome for well-defined strain from Australia, called Haecon-5, has constrained research in number areas including host-parasite interactions, drug discovery population genetics. To enable these areas, we report here chromosome-contiguous (∼280 Mb) Haecon-5 models 19,234 protein-coding genes. Comparative genomic analyses show significant similarity (synteny) UK H. MHco3(ISE).N1 (abbreviated as "ISE"), but also discover marked differences structure/gene arrangements, distribution nucleotide variability (single polymorphisms (SNPs) indels) orthology between ISE. We used extensive transcriptomic resources predict subset essential single-copy genes employing "cross-species" machine learning (ML) approach using range features nucleotide/protein sequences, protein orthology, subcellular localisation, single-cell RNA-seq and/or histone methylation data available model organisms Caenorhabditis elegans Drosophila melanogaster. From set 1,464 conserved single copy genes, transcribed key life-cycle stages identified 232 whose homologs have critical functions C. D. melanogaster, prioritised 10 them further characterisation; nine likely play roles neurophysiological processes, germline, hypodermis respiration, one is an unknown (orphan) gene which no detailed functional information exists. Future studies genes/gene products warranted elucidate their biology, interplay disease. Clearly, present reference associated now underpin broad fundamental investigations contortus could assist accelerating novel intervention targets candidates combat

Language: Английский

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A probe-based capture enrichment method for detection of A-to-I editing in low abundance transcripts

Methods in enzymology on CD-ROM/Methods in enzymology, Journal Year: 2025, Volume and Issue: unknown, P. 55 - 75

Published: Jan. 1, 2025

Language: Английский

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