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result(s) for
"Jang, Yong Eun"
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Development of Anticancer Peptides Using Artificial Intelligence and Combinational Therapy for Cancer Therapeutics
by
Shin, Tae Hwan
,
Kim, Seok Gi
,
Lee, Gwang
in
Amino acids
,
anticancer peptides
,
Artificial intelligence
2022
Cancer is a group of diseases causing abnormal cell growth, altering the genome, and invading or spreading to other parts of the body. Among therapeutic peptide drugs, anticancer peptides (ACPs) have been considered to target and kill cancer cells because cancer cells have unique characteristics such as a high negative charge and abundance of microvilli in the cell membrane when compared to a normal cell. ACPs have several advantages, such as high specificity, cost-effectiveness, low immunogenicity, minimal toxicity, and high tolerance under normal physiological conditions. However, the development and identification of ACPs are time-consuming and expensive in traditional wet-lab-based approaches. Thus, the application of artificial intelligence on the approaches can save time and reduce the cost to identify candidate ACPs. Recently, machine learning (ML), deep learning (DL), and hybrid learning (ML combined DL) have emerged into the development of ACPs without experimental analysis, owing to advances in computer power and big data from the power system. Additionally, we suggest that combination therapy with classical approaches and ACPs might be one of the impactful approaches to increase the efficiency of cancer therapy.
Journal Article
Analysis of Nanotoxicity with Integrated Omics and Mechanobiology
2021
Nanoparticles (NPs) in biomedical applications have benefits owing to their small size. However, their intricate and sensitive nature makes an evaluation of the adverse effects of NPs on health necessary and challenging. Since there are limitations to conventional toxicological methods and omics analyses provide a more comprehensive molecular profiling of multifactorial biological systems, omics approaches are necessary to evaluate nanotoxicity. Compared to a single omics layer, integrated omics across multiple omics layers provides more sensitive and comprehensive details on NP-induced toxicity based on network integration analysis. As multi-omics data are heterogeneous and massive, computational methods such as machine learning (ML) have been applied for investigating correlation among each omics. This integration of omics and ML approaches will be helpful for analyzing nanotoxicity. To that end, mechanobiology has been applied for evaluating the biophysical changes in NPs by measuring the traction force and rigidity sensing in NP-treated cells using a sub-elastomeric pillar. Therefore, integrated omics approaches are suitable for elucidating mechanobiological effects exerted by NPs. These technologies will be valuable for expanding the safety evaluations of NPs. Here, we review the integration of omics, ML, and mechanobiology for evaluating nanotoxicity.
Journal Article
Integrative Analysis of Metabolome and Proteome in the Cerebrospinal Fluid of Patients with Multiple System Atrophy
2025
Multiple system atrophy (MSA) is a progressive neurodegenerative synucleinopathy. Differentiating MSA from other synucleinopathies, especially in the early stages, is challenging because of its overlapping symptoms with other forms of Parkinsonism. Thus, there is a pressing need to clarify the underlying biological mechanisms and identify specific biomarkers for MSA. The metabolic profile of cerebrospinal fluid (CSF) is known to be altered in MSA. To further investigate the biological mechanisms behind the metabolic changes, we created a network of altered CSF metabolites in patients with MSA and analysed these changes using bioinformatic software. Acknowledging the limitations of metabolomics, we incorporated proteomic data to improve the overall comprehensiveness of the study. Our in silico predictions showed elevated ROS, cytoplasmic inclusions, white matter demyelination, ataxia, and neurodegeneration, with ATP concentration, neurotransmitter release, and oligodendrocyte count predicted to be suppressed in MSA CSF samples. Machine learning and dimension reduction are important multi-omics approaches as they handle large amounts of data, identify patterns, and make predictions while reducing variance without information loss and generating easily visualised plots that help identify clusters, patterns, or outliers. Thus, integrated multiomics and machine learning approaches are essential for elucidating neurodegenerative mechanisms and identifying potential diagnostic biomarkers of MSA.
Journal Article
Reduction in the Migration Activity of Microglia Treated with Silica-Coated Magnetic Nanoparticles and their Recovery Using Citrate
by
Basith, Shaherin
,
Shin, Tae Hwan
,
Kim, Seok Gi
in
Artificial intelligence
,
Blood-brain barrier
,
Brain research
2022
Nanoparticles have garnered significant interest in neurological research in recent years owing to their efficient penetration of the blood–brain barrier (BBB). However, significant concerns are associated with their harmful effects, including those related to the immune response mediated by microglia, the resident immune cells in the brain, which are exposed to nanoparticles. We analysed the cytotoxic effects of silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)] in a BV2 microglial cell line using systems toxicological analysis. We performed the invasion assay and the exocytosis assay and transcriptomics, proteomics, metabolomics, and integrated triple-omics analysis, generating a single network using a machine learning algorithm. The results highlight alteration in the mechanisms of the nanotoxic effects of nanoparticles using integrated omics analysis.
Journal Article
Cerebrospinal Fluid Metabolome in Parkinson’s Disease and Multiple System Atrophy
by
Shin, Tae Hwan
,
Kim, Seok Gi
,
Lee, Gwang
in
Biomarkers
,
Biomarkers - cerebrospinal fluid
,
Computational Biology - methods
2022
Parkinson’s disease (PD) and multiple system atrophy (MSA) belong to the neurodegenerative group of synucleinopathies; differential diagnosis between PD and MSA is difficult, especially at early stages, owing to their clinical and biological similarities. Thus, there is a pressing need to identify metabolic biomarkers for these diseases. The metabolic profile of the cerebrospinal fluid (CSF) is reported to be altered in PD and MSA; however, the altered metabolites remain unclear. We created a single network with altered metabolites in PD and MSA based on the literature and assessed biological functions, including metabolic disorders of the nervous system, inflammation, concentration of ATP, and neurological disorder, through bioinformatics methods. Our in-silico prediction-based metabolic networks are consistent with Parkinsonism events. Although metabolomics approaches provide a more quantitative understanding of biochemical events underlying the symptoms of PD and MSA, limitations persist in covering molecules related to neurodegenerative disease pathways. Thus, omics data, such as proteomics and microRNA, help understand the altered metabolomes mechanism. In particular, integrated omics and machine learning approaches will be helpful to elucidate the pathological mechanisms of PD and MSA. This review discusses the altered metabolites between PD and MSA in the CSF and omics approaches to discover diagnostic biomarkers.
Journal Article
Integrative Metabolome and Proteome Analysis of Cerebrospinal Fluid in Parkinson’s Disease
by
Kim, Seok Gi
,
Jang, Yong Eun
,
Kwon, Minjun
in
Bioinformatics
,
Biomarkers
,
Biomarkers - cerebrospinal fluid
2024
Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra. Recent studies have highlighted the significant role of cerebrospinal fluid (CSF) in reflecting pathophysiological PD brain conditions by analyzing the components of CSF. Based on the published literature, we created a single network with altered metabolites in the CSF of patients with PD. We analyzed biological functions related to the transmembrane of mitochondria, respiration of mitochondria, neurodegeneration, and PD using a bioinformatics tool. As the proteome reflects phenotypes, we collected proteome data based on published papers, and the biological function of the single network showed similarities with that of the metabolomic network. Then, we analyzed the single network of integrated metabolome and proteome. In silico predictions based on the single network with integrated metabolomics and proteomics showed that neurodegeneration and PD were predicted to be activated. In contrast, mitochondrial transmembrane activity and respiration were predicted to be suppressed in the CSF of patients with PD. This review underscores the importance of integrated omics analyses in deciphering PD’s complex biochemical networks underlying neurodegeneration.
Journal Article
Biological Function Analysis of MicroRNAs and Proteins in the Cerebrospinal Fluid of Patients with Parkinson’s Disease
by
Kim, Seok Gi
,
Kwon, Minjun
,
Jang, Yong Eun
in
Bioinformatics
,
Biomarkers
,
Biomarkers - cerebrospinal fluid
2024
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by alpha-synuclein aggregation into Lewy bodies in the neurons. Cerebrospinal fluid (CSF) is considered the most suited source for investigating PD pathogenesis and identifying biomarkers. While microRNA (miRNA) profiling can aid in the investigation of post-transcriptional regulation in neurodegenerative diseases, information on miRNAs in the CSF of patients with PD remains limited. This review combines miRNA analysis with proteomic profiling to explore the collective impact of CSF miRNAs on the neurodegenerative mechanisms in PD. We constructed separate networks for altered miRNAs and proteomes using a bioinformatics method. Altered miRNAs were poorly linked to biological functions owing to limited information; however, changes in protein expression were strongly associated with biological functions. Subsequently, the networks were integrated for further analysis. In silico prediction from the integrated network revealed relationships between miRNAs and proteins, highlighting increased reactive oxygen species generation, neuronal loss, and neurodegeneration and suppressed ATP synthesis, mitochondrial function, and neurotransmitter release in PD. The approach suggests the potential of miRNAs as biomarkers for critical mechanisms underlying PD. The combined strategy could enhance our understanding of the complex biochemical networks of miRNAs in PD and support the development of diagnostic and therapeutic strategies for precision medicine.
Journal Article
SurgT challenge: Benchmark of Soft-Tissue Trackers for Robotic Surgery
2023
This paper introduces the ``SurgT: Surgical Tracking\" challenge which was organised in conjunction with MICCAI 2022. There were two purposes for the creation of this challenge: (1) the establishment of the first standardised benchmark for the research community to assess soft-tissue trackers; and (2) to encourage the development of unsupervised deep learning methods, given the lack of annotated data in surgery. A dataset of 157 stereo endoscopic videos from 20 clinical cases, along with stereo camera calibration parameters, have been provided. Participants were assigned the task of developing algorithms to track the movement of soft tissues, represented by bounding boxes, in stereo endoscopic videos. At the end of the challenge, the developed methods were assessed on a previously hidden test subset. This assessment uses benchmarking metrics that were purposely developed for this challenge, to verify the efficacy of unsupervised deep learning algorithms in tracking soft-tissue. The metric used for ranking the methods was the Expected Average Overlap (EAO) score, which measures the average overlap between a tracker's and the ground truth bounding boxes. Coming first in the challenge was the deep learning submission by ICVS-2Ai with a superior EAO score of 0.617. This method employs ARFlow to estimate unsupervised dense optical flow from cropped images, using photometric and regularization losses. Second, Jmees with an EAO of 0.583, uses deep learning for surgical tool segmentation on top of a non-deep learning baseline method: CSRT. CSRT by itself scores a similar EAO of 0.563. The results from this challenge show that currently, non-deep learning methods are still competitive. The dataset and benchmarking tool created for this challenge have been made publicly available at https://surgt.grand-challenge.org/.
Poly(fluorenyl aryl piperidinium) membranes and ionomers for anion exchange membrane fuel cells
by
Lee, Won Hee
,
Chung, Yong-Chae
,
Yoo, Sung Jong
in
639/301/299/893
,
639/4077/893
,
639/638/161/893
2021
Low-cost anion exchange membrane fuel cells have been investigated as a promising alternative to proton exchange membrane fuel cells for the last decade. The major barriers to the viability of anion exchange membrane fuel cells are their unsatisfactory key components—anion exchange ionomers and membranes. Here, we present a series of durable poly(fluorenyl aryl piperidinium) ionomers and membranes where the membranes possess high OH
−
conductivity of 208 mS cm
−1
at 80 °C, low H
2
permeability, excellent mechanical properties (84.5 MPa TS), and 2000 h ex-situ durability in 1 M NaOH at 80 °C, while the ionomers have high water vapor permeability and low phenyl adsorption. Based on our rational design of poly(fluorenyl aryl piperidinium) membranes and ionomers, we demonstrate alkaline fuel cell performances of 2.34 W cm
−2
in H
2
-O
2
and 1.25 W cm
−2
in H
2
-air (CO
2
-free) at 80 °C. The present cells can be operated stably under a 0.2 A cm
−2
current density for ~200 h.
Developing high-performance anion exchange membranes and ionomers is crucial for low-cost alkaline fuel cells. Here, the authors explore rigid and high ion conductive poly(fluorenyl aryl piperidinium) copolymers, extending their applications to anion exchange membrane fuel cells.
Journal Article
Genome-wide functional analysis of phosphatases in the pathogenic fungus Cryptococcus neoformans
2020
Phosphatases, together with kinases and transcription factors, are key components in cellular signalling networks. Here, we present a systematic functional analysis of the phosphatases in
Cryptococcus neoformans
, a fungal pathogen that causes life-threatening fungal meningoencephalitis. We analyse 230 signature-tagged mutant strains for 114 putative phosphatases under 30 distinct in vitro growth conditions, revealing at least one function for 60 of these proteins. Large-scale virulence and infectivity assays using insect and mouse models indicate roles in pathogenicity for 31 phosphatases involved in various processes such as thermotolerance, melanin and capsule production, stress responses,
O-
mannosylation, or retromer function. Notably, phosphatases Xpp1, Ssu72, Siw14, and Sit4 promote blood-brain barrier adhesion and crossing by
C. neoformans
. Together with our previous systematic studies of transcription factors and kinases, our results provide comprehensive insight into the pathobiological signalling circuitry of
C. neoformans
.
Phosphatases are key components in cellular signalling networks. Here, the authors present a systematic functional analysis of phosphatases of the fungal pathogen
Cryptococcus neoformans
, revealing roles in virulence, stress responses,
O
-mannosylation, retromer function and other processes.
Journal Article