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

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

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

Language: Английский

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Intestinal RICT-1 regulates the larval germline progenitor pool via the vitellogenin VIT-3 inC. elegans

Published: Jan. 9, 2025

Populations of proliferating cells such as stem and tumors are often nutrient responsive. Highly conserved signaling pathways communicate information about the surrounding environmental, organismal, cellular conditions. One pathway is Target Rapamycin (TOR) pathway. The TOR kinase exists in two complexes, complex 1 (TORC1) 2 (TORC2). TORC1 has been researched extensively its regulation, particularly by amino acids, well characterized. activity promotes both cell fate proliferation Caenorhabditis elegans hermaphrodite germline system to facilitate expansion larval Progenitor Zone (PZ) pool response nutrients. By contrast, a role for TORC2 development not investigated. Here, we show that RICT-1, sole ortholog TORC2-specific component RICTOR, also PZ, acting largely through SGK-1. Further, unlike germline-autonomous components, intestinal rict-1 necessary sufficient full PZ establishment. Furthermore, neither DAF-2/IIS nor DAF-7/TGF-ß mediate effects RICT-1. Rather, RICT-1 likely acts via vitellogenins, intestinally produced yolk proteins previously characterized provisioning adult germ line, but line development. comparative RNA-seq on staged L4 larvae, found vitellogenin genes among highly differentially abundant mRNAs. Genetic analysis supports vit-3 linear with . Our results establish C. fruitful model investigating connection lipid biology.

Language: Английский

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Developmental and conditional regulation of DAF-2/INSR ubiquitination in Caenorhabditis elegans

G3 Genes Genomes Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Abstract Insulin/IGF signaling (IIS) regulates developmental and metabolic plasticity. Conditional regulation of insulin-like peptide expression secretion promotes different phenotypes in environments. However, IIS can also be regulated by other, less-understood mechanisms. For example, stability the only known insulin/IGF receptor C. elegans, DAF-2/INSR, is CHIP-dependent ubiquitination. Disruption chn-1/CHIP reduces longevity elegans increasing DAF-2/INSR abundance activity adults. Likewise, mutation a ubiquitination site causes daf-2(gk390525) to display gain-of-function we show that this allele displays loss-of-function larvae, its effect on transitions from negative positive during development. In contrast, acts like larvae cultured at high temperature, inhibiting temperature-dependent dauer formation. an increase starved L1 unlike daf-2(gk390525). CHN-1/CHIP ubiquitinates multiple sites. These results suggest sites are functionally relevant vary adults, temperatures, nutrient-dependent fashion, revealing additional layers regulation.

Language: Английский

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Multiple regulators constrain the abundance of C. elegans DLK-1 in ciliated sensory neurons

G3 Genes Genomes Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Abstract The conserved MAP3K DLKs are widely known for their functions in synapse formation, axonal regeneration and degeneration, neuronal survival, notably under traumatic injury chronic disease conditions. In contrast, roles other compartments much less explored. Through an unbiased forward genetic screening C. elegans altered patterns of GFP-tagged DLK-1 expressed from the endogenous locus, we have recently uncovered a mechanism by which abundance is tightly regulated intraflagellar transport ciliated sensory neurons. Here, report additional mutants identified screen. Most exhibit increased accumulation GFP::DLK-1 endings, levels misaccumulated exacerbated loss function cebp-1, b-Zip transcription factor acting downstream DLK-1. We identify several new mutations genes encoding proteins functioning cilia assembly, components BBSome, MAPK-15 DYF-5 kinases. novel mutation chaperone HSP90 that causes misaccumulation up-regulation CEBP-1 selectively also find guanylate cyclase ODR-1 constrains throughout dendrites AWC Moreover, odr-1 mutants, display distorted morphology, ameliorated dlk-1 or cebp-1. These data expand landscape signaling neurons underscore high degree cell- neurite- specific regulation.

Language: Английский

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Animal models of kabuki syndrome and their applicability to novel drug discovery

Expert Opinion on Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 25, 2025

Kabuki Syndrome (KS) is a rare genetic disorder characterized by distinctive facial features, intellectual disability, and multiple congenital anomalies. It caused pathogenic variants in the KMT2D KDM6A genes. Despite its significant disease burden, there are currently no approved therapies for KS, highlighting need advanced research therapeutic development. This review examines use of animal models KS research, including mice, fish, frogs, nematodes. These replicate key mechanistic clinical aspects Syndrome, facilitating preclinical studies to demonstrate efficacy. The literature search focused on identifying that utilized these investigate pathophysiology evaluate potential treatments. Refining essential enhance their relevance human accelerate development effective Syndrome. Insights from invaluable understanding underlying molecular mechanisms targets. Continued collaboration crucial translating findings into practice, offering hope future

Language: Английский

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Sequence variants in HECTD1 result in a variable neurodevelopmental disorder

The American Journal of Human Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Protein sequence editing defines distinct and overlapping functions of SKN-1A/Nrf1 and SKN-1C/Nrf2.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

ABSTRACT The Nrf/NFE2L family of transcription factors regulates redox balance, xenobiotic detoxification, metabolism, proteostasis, and aging. Nrf1/NFE2L1 is primarily responsible for stress-responsive upregulation proteasome subunit genes essential adaptation to proteotoxic stress. Nrf2/NFE2L2 mainly involved in activating oxidative stress responses promoting detoxification. Nrf1 Nrf2 contain very similar DNA binding domains can drive transcriptional responses. In C. elegans , a single gene, skn-1 encodes distinct protein isoforms, SKN-1A SKN-1C, that function analogously mammalian Nrf2, respectively, share an identical domain. Thus, the extent which SKN-1A/Nrf1 SKN-1C/Nrf2 functions are or overlapping has been unclear. Regulation by requires post-translational conversion N-glycosylated asparagine residues aspartate PNG-1/NGLY1 peptide:N-glycanase, process we term ‘sequence editing’. Here, reveal consequences sequence editing transcriptomic output activated SKN-1A. We confirm activation strictly dependent on editing. addition, find edited also activate linked homeostasis detoxification regulated but these genes’ antagonized Using mutant alleles selectively inactivate either show both isoforms promote optimal resistance, acting as effectors signaling pathways. These findings suggest governs SKN-1/Nrf tuning transcriptome.

Language: Английский

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Crossovers are regulated by a conserved and disordered synaptonemal complex domain

Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(4)

Published: Feb. 4, 2025

Abstract During meiosis, the number and distribution of crossovers (COs) must be precisely regulated through CO assurance interference to prevent chromosome missegregation genomic instability in progeny. Here we show that this regulation COs depends on a disordered conserved domain within synaptonemal complex (SC). This is located at C-terminus central element protein SYP-4 Caenorhabditis elegans. While not necessary for synapsis, crucial both interference. Although contains many potential phosphorylation sites, found primary regulator events. Instead, discovered nine phenylalanines are required recruit pro-CO factor predicted an E3 ligase regulate physical properties SC. We propose plays role maintaining SC state allows transmitting signals formation. underlying mechanisms remain fully understood, our findings align with existing models suggesting critical determining along chromosomes, thereby safeguarding genome future generations.

Language: Английский

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The neuron-intrinsic membrane skeleton is required for motor neuron integrity throughout lifespan

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 24, 2025

Axons experience physical stress throughout an organism's lifetime, and disruptions in axonal integrity are hallmarks of both neurodegenerative diseases traumatic injuries. The spectrin-based membrane periodic skeleton (MPS) is proposed to have a crucial role maintaining strength, flexibility, resilience. To investigate the importance intrinsic MPS for GABAergic motor neuron C. elegans , we employed auxin-inducible degron system degrade β-spectrin/UNC-70 cell-type specific time-dependent manner. Degradation β-spectrin from all neurons beginning at larval development resulted widespread axon breakage regeneration VD/DD adult animals. Similarly, targeted degradation GABA alone extensive breakage. Moreover, found that depleting mature nervous also induced breaks. By contrast, epidermal was not required neurons. These findings demonstrate cell-intrinsic neuronal during adulthood.

Language: Английский

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Protocol to identify transcription factor target genes using TargetOrtho2

STAR Protocols, Journal Year: 2025, Volume and Issue: 6(1), P. 103680 - 103680

Published: March 1, 2025

TargetOrtho2 uses transcription factor binding site information to predict targets in C. elegans, based on an silico phylogenetic footprinting approach. Here, we present a protocol identify target genes using new version of TargetOrtho2. We provide instructions for installing and its required suite programs, predicting genes, updating adding genomes

Language: Английский

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