Biology subjects

Ryu, Y.

Publications and source records attributed to Ryu, Y..

9 recordsLinked to original sources

bioRxiv2026

AI-driven framework modeling perturbation in brain organoids reveals candidate genes for autism

Autism gene discovery is constrained by the rarity and heterogeneity of damaging variants, requiring large cohorts to identify susceptibility genes. Neural organoids and single-cell foundation models enable perturbation modeling in neurodevelopmental contexts. Here, we show that perturbation-informed foundation modeling of neural organoids can provide functional context for prioritizing candidate genes with genomic and clinical support. We constructed a 3.6-million-cell organoid atlas and trained models to predict genome-wide perturbation responses. Benchmarking 17 models identified a telencephalic neuron-specific model best preserving autism-relevant perturbation structure. Genome-wide profiling revealed two clusters associated with mid-fetal synaptic neuronal processes and early radial glia ubiquitin signaling. These clusters were supported by damaging-variant enrichment and clinical phenotypes across 89,916 family-based samples. Logistic-regression prioritization identified 343 candidates, including 167 in the key clusters, with convergence across TADA signals and recurrent evidence for NBEA and KLHDC10. This framework integrates predicted perturbation effects with genomic evidence to support autism candidate prioritization.

bioinformatics↗

bioRxiv2026

megaMine: a scalable, rule-based framework for mining gene-cancer-drug evidence from biomedical literature

The rapid expansion of the oncology literature has outpaced manual curation of clinically relevant gene-cancer-drug associations and oncogenic driver evidence. Existing automated approaches often lack transparency or are difficult to scale across heterogeneous data sources. To address this gap, we developed megaMine, a transparent, rule-based, and context-aware literature-mining framework that integrates therapeutic and driver evidence from PubMed, PubTator, and Europe PMC by combining entity recognition, hierarchical heuristics, and contextual labeling. In therapy mode, megaMine was applied to approximately 100,000 oncology articles published between 2015 and 2025, yielding more than 23,000 structured sentence-level evidence records, with standardized annotations for drug response, resistance, and study context. Internal evaluation of context labels showed strong separability between efficacy and non-efficacy evidence using ridge logistic regression (AUROC = 0.915; AUPRC = 0.941). Benchmarking against NCI/OncoKB-supported drug-cancer associations showed that curated clinical associations had higher megaMine composite evidence scores than unlabeled comparison pairs [median (IQR): 25.6 (9.07-72.5) vs. 3.61 (1.69-8.69); Wilcoxon rank-sum test, P < 2.2 x 10^-16]. In driver mode, megaMine retrieved mutation- and biomarker-related evidence from an ERBB-focused gastric cancer query, generating 750 evidence rows from 200 PMIDs. These results demonstrate that deterministic and interpretable approaches can support scalable evidence extraction for downstream applications such as knowledge graph construction and literature-based evidence synthesis.

bioinformatics↗

bioRxiv2026

Auto-sumoylation of UBC9 coordinates meiotic prophase and protects ovarian reserves

The small ubiquitin-like modifier SUMO regulates key events of meiosis, including pairing and crossing over between homologous chromosomes. Auto-sumoylation of the SUMO E2-conjugating enzyme UBC9 at lysine 14 alters its substrate selectivity in vitro, but the role of this modification in vivo is unknown. Here, we show that UBC9-K14 auto-sumoylation helps coordinate meiotic prophase and is important for maintenance of the ovarian reserve. Ubc9K14R/K14R knock-in mice show a variety of defects in meiotic prophase I, including altered assembly of DNA strand-exchange complexes, delayed and defective homolog synapsis, and unstable crossover recombination complexes. In spermatocytes, these defects are associated with reduced efficiency of crossing over between the X and Y chromosomes. Oocytes from Ubc9K14R/K14R females show related but distinct defects in recombination and synapsis. Moreover, maintenance of the primordial follicle reserve is defective in Ubc9K14R/K14R females, and their fecundity is reduced. Finally, we identify the meiosis-specific homolog-axis protein SYCP3 as a direct target of UBC9 in vitro and show that SYCP3 modification is strongly stimulated by K14 auto-sumoylation. We infer that auto-sumoylation enables UBC9 to modify a subset of targets in vivo, helping to coordinate key events of meiotic prophase and enhance the survival of primordial follicles to maximize fecundity.

genetics↗

bioRxiv2023

A unifying principle for global greenness patterns and trends

Vegetation cover regulates the exchanges of energy, water and carbon between land and atmosphere. Remotely-sensed fractional absorbed photosynthetically active radiation (fAPAR), a land-surface greenness metric, depends on carbon allocation to foliage while also controlling photon flux for photosynthesis. Greenness is thus both a driver and an outcome of gross primary production (GPP). An equation with just two (globally) fitted parameters describes annual maximum fAPAR (fAPARmax) as the smaller of a water-limited value, transpiring a constant fraction of annual precipitation, and an energy-limited value, maximizing annual plant growth. This minimalist description reproduces global greenness patterns, and the consistent temporal trends among remote-sensing products, as accurately as the best-performing dynamic global vegetation models. Widely observed greening is attributed to the influence of rising carbon dioxide on the light- and water-use efficiencies of GPP, augmented by wetting in some dry regions and warming in high latitudes. Limited regions show browning, attributed to drying.

ecology↗

bioRxiv2022

Application of Passive Head Motion to Generate Defined Accelerations at the Heads of Rodents

Exercise is widely recognized as effective for various diseases and physical disorders, including those related to brain dysfunction. However, molecular mechanisms behind the beneficial effects of exercise are poorly understood. Many physical workouts, particularly those classified as aerobic exercises such as jogging and walking, produce impulsive forces at the time of foot contact with the ground. Therefore, it was speculated that mechanical impact might be implicated in how exercise contributes to organismal homeostasis. For testing this hypothesis on the brain, a custom-designed passive head motion (hereafter referred to as PHM) system was developed that can generate vertical accelerations with controlled and defined magnitudes and modes and reproduce mechanical stimulation that might be applied to the heads of rodents during treadmill running at moderate velocities, a typical intervention to test the effects of exercise in animals. By using this system, it was demonstrated that PHM recapitulates the serotonin (5-hydroxytryptamine, hereafter referred to as 5-HT) receptor subtype 2A (5-HT2A) signaling in the prefrontal cortex (PFC) neurons of mice. This work provides detailed protocols for applying PHM and measuring its resultant mechanical accelerations at rodents heads. SUMMARYThe present protocol describes a custom-designed passive head motion system, which reproduces mechanical accelerations at rodents heads generated during their treadmill running at moderate velocities. It allows dissecting mechanical factors/elements from the beneficial effects of physical exercise.

bioengineering↗

bioRxiv2022

Genetic or transcranial magnetic stimulation of B-RAF-MEK signaling promotes CST axon sprouting and functional regeneration

Facilitating axon regeneration in the injured central nervous system remains a challenging task. RAF-MEK signaling plays an important role in axon elongation during nervous system development. Here we show that activation of B-RAF in mature corticospinal neurons elicited the expression of a discrete set of transcription factors previously implicated in the regeneration of zebrafish optic nerve axons. Genetic activation of B-RAF-MEK signaling promoted robust regeneration and sprouting of corticospinal tract axons after injury. Newly sprouting axon collaterals formed synaptic connections with spinal interneurons, correlating with the recovery of skilled motor function. Seeking a non-invasive way to stimulate axon regeneration, we found that suprathreshold high-frequency repetitive transcranial magnetic stimulation activates the B-RAF canonical effectors MEK1/2 and requires MEK1/2 activity to promote corticospinal axon regeneration and sprouting after injury. These data demonstrate a central role of neuron-intrinsic RAF-MEK signaling in enhancing the growth capacity of mature corticospinal neurons and propose HF-rTMS as a potential therapy for spinal cord injury. One Sentence SummaryGenetic or HF-rTMS-mediated activation of B-RAF- MEK signaling promotes CST axon sprouting and functional regeneration after a spinal cord injury.

neuroscience↗

bioRxiv2021

Amelioration of DSS-induced Acute Colitis in Mice by Recombinant Monomeric Human Interleukin-22

Interleukin-22 (IL-22), a pleiotropic cytokine, is known to have a profound effect on the regeneration of damaged intestinal barriers. The tissue-protective properties of IL-22 are expected to be potentially exploited in the attenuation and treatment of colitis. However, because of the disease-promoting role of IL-22 in chronic inflammation, a comprehensive evaluation is required to translate IL-22 into the clinical domain. Here, we present the effective production of soluble human IL-22 in bacteria to prove whether recombinant IL-22 has the ability to ameliorate colitis and inflammation. IL-22 was expressed in the form of a biologically active monomer and a non-functional dimer. Monomeric IL-22 (mIL-22) was highly purified through a series of three separate chromatographic methods and an enzymatic reaction. We reveal that the resulting mIL-22 is correctly folded and is able to phosphorylate signal transducer and activator of transcription 3 in HT-29 cells. Subsequently, we demonstrate that mIL-22 enables the attenuation of dextran sodium sulfate-induced acute colitis in mice, as well as the suppression of pro-inflammatory cytokine production. Collectively, our results suggest that the recombinant mIL-22 is suitable to study the biological roles of endogenous IL-22 in immune responses and can be developed as a biological agent associated with inflammatory disorders.

immunology↗

bioRxiv2021

A Combination Strategy of Solubility Enhancers for Effective Production of Soluble and Bioactive Human Enterokinase

Enterokinase is one of the hydrolases that catalyze hydrolysis to regulate biological processes in intestinal visceral mucosa. Enterokinase plays an essential role in accelerating the process of protein digestion as it converts trypsinogen into active trypsin by accurately recognizing and cleaving a specific peptide sequence, (Asp)4-Lys. Due to its exceptional substrate specificity, enterokinase is widely used as a versatile molecular tool in various bioprocessing, especially in removing fusion tags from recombinant proteins. Despite its biotechnological importance, mass production of soluble enterokinase in bacteria still remains an unsolved challenge. Here, we present an effective production strategy of human enterokinase using tandemly linked solubility enhancers consisting of thioredoxin, phosphoglycerate kinase or maltose-binding protein. The resulting enterokinases exhibited significantly enhanced solubility and bacterial expression level while retaining enzymatic activity, which demonstrates that combinatorial design of fusion proteins has the potential to provide an efficient way to produce recombinant proteins in bacteria.

bioengineering↗

bioRxiv2018

C. elegans Mediator 15 permits low temperature-induced longevity via regulation of lipid and protein homeostasis

Low temperatures slow aging and extend lifespan in many organisms, including Caenorhabditis elegans. However, the metabolic and homeostatic aspects of low temperature-induced longevity remain poorly understood. Here, we show that changes in lipid composition regulated by MDT-15/Mediator 15, transcriptional co-regulator, is essential for low temperature-induced longevity and proteostasis in C. elegans. We find that inhibition of mdt-15 prevents animals from living long at low temperatures. We show that MDT-15 up-regulates fat-7, a fatty acid desaturase, at low temperatures, which increases the ratio of unsaturated to saturated fatty acids. We further demonstrate that maintaining this increased fatty acid ratio is essential for protein homeostasis and longevity at low temperatures. Thus, the homeostasis of lipid composition by MDT-15 appears to be a limiting factor for C. elegans proteostasis and longevity at low temperatures. Our findings highlight the crucial roles of fat regulation in maintaining normal organismal physiology under different environmental conditions.

developmental biology↗