Biology subjects

Choe, S.

Publications and source records attributed to Choe, S..

4 recordsLinked to original sources

bioRxiv2025

RobPicker: A Meta Learning Framework for Robust Identification of Macromolecules in Cryo-Electron Tomograms

Accurate particle picking of macromolecules of all kinds, shapes, and sizes in cryogenic electron tomograms (cryo-ET) is critical for understanding the molecular architecture of biological systems in their native state. Current deep learning methods have shown potential in identifying macromolecules from tomograms, but they are vulnerable to issues of noise in the training dataset obtained through human or automatic labeling and imbalanced distribution of macromolecule species. To address these limitations, we developed RobPicker, a meta-learning framework that effectively mitigates these issues by automatically learning deep neural networks to correct label errors and give greater emphasis to underrepresented macromolecule species. In evaluations across diverse cryo-ET datasets with noisy labels and imbalanced species distributions, RobPicker substantially outperforms state-of-the-art methods, particularly in identifying small and rare macromolecules. The efficiency and robustness of RobPicker can also be used for rapid fine-tuning of the tilt-series alignment, leading to improved tomogram reconstruction and enabling high-resolution cellular structural biology analysis.

bioinformatics↗

bioRxiv2021

The Rice propiconazole resistant 1-D mutant, with activated expression of a DPb transcription factor gene, exhibits increased seed yields

Mutants defective in brassinosteroid (BR) biosynthesis or signaling pathways often display semi-dwarfism, as do the highly productive gibberellin mutants that enabled the Green Revolution. However, reduced vegetative growth in BR mutants does not necessarily correspond to increased seed yields. To better understand the mode of action of BR, we isolated a rice propiconazole resistant1-D (pzr1-D) mutant by screening an activation-tagging mutant population in the presence of the BR biosynthesis inhibitor propiconazole (Pcz). The expression of a putative transcription factor gene homologous to Arabidopsis Dimerization Partner (DPb) was activated in pzr1-D. pzr1-D exhibited characteristic phenotypes such as reduced height, and increased seed yields and tiller numbers. Like Arabidopsis DPb, rice PZR1 is expressed differentially in the tissues examined. Furthermore, pzr1-D displayed altered cell division phenotypes, including the production of small calli. In addition, the cell number and size in mutant roots and leaves differed from those in wild-type plants of the same age. RNA sequencing revealed that the promoters of differentially expressed genes are enriched with cognate sequences for both BZR1 and EF-DPb transcription factors, suggesting that PZR1 functions in BR-mediated cell division in rice. PZR1 expression may thus be manipulated to increase seed yield in economically important rice varieties. SIGNIFICANCE STATEMENTMutants defective in brassinosteroid biosynthesis or signaling pathways often display semi-dwarfism. However, in many cases these mutants do not necessarily produce increased seed yields. We show a rice propiconazole resistant1-D (pzr1-D) mutant which exhibits reduced height phenotypes along with increase tiller number and seed yields. pzr1-D shows activation of a putative homologous to Arabidopsis Dimerization Partner (DPb) with functions in cell division, pointing that PZR1 may function in BR-mediated cell division in rice.

plant biology↗

bioRxiv2021

Production and assessment of monoclonal antibodies against the SpyCas9 protein of Streptococcus pyogenes

The biotechnological applications of the programmable DNA-cleaving enzymes known as clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) continue to expand from agricultural trait development to therapeutic gene therapies. The Cas9 CRISPR system isolated from Streptococcus pyogenes (SpyCas9) is classified as class II, which is popular due to high efficiency and robustness. Antibodies that specifically detect SpyCas9 could expand the applicability of this enzyme. Here, we report on the development of monoclonal antibodies against SpyCas9. Four hybridoma cells were selected for their expression of anti-SpyCas9. Hybridoma supernatant contained reactive and highly specific antibodies to SpyCas9. Anti-SpyCas9 antibody was purified and was non-selective against six other bacterial Cas9 proteins. SpyCas9 protein could be detected in HEK293T cells in decreasing amounts over a 48 hour period, indicating the antibody could be used to detect residual levels of SpyCas9 remaining following cell treatment with a CRISPR/SpyCas9 system. The anti-SpyCas9 antibody may help researchers facilitate Cas9 for further study for the use of techniques such as enzyme-linked immunosorbent assays (ELISAs), western blot, immunoprecipitation, and immunohistochemical staining.

molecular biology↗

bioRxiv2018

Isoform switching as a mechanism of acquired resistance to isocitrate dehydrogenase inhibition

Somatic mutations in cytosolic or mitochondrial isoforms of isocitrate dehydrogenase (IDH1 or IDH2, respectively) contribute to oncogenesis via production of the metabolite 2-hydroxyglutarate (2HG). Isoform-selective IDH inhibitors suppress 2HG production and induce clinical responses in patients with IDH1- and IDH2-mutant malignancies. Despite the promising activity of IDH inhibitors, the mechanisms that mediate resistance to IDH inhibition are poorly understood. Here, we describe four clinical cases that identify mutant IDH isoform switching, either from mutant IDH1 to mutant IDH2 or vice versa, as a mechanism of acquired clinical resistance to IDH inhibition in solid and liquid tumors.\n\nSignificanceIDH-mutant cancers can develop resistance to isoform-selective IDH inhibition by \"isoform switching\" from mutant IDH1 to mutant IDH2 or vice versa, thereby restoring 2-hydroxyglutarate (2HG) production by the tumor. These findings underscore a role for continued 2HG production in tumor progression and suggest therapeutic strategies to prevent or overcome resistance.

cancer biology↗