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Targeting DNA junction sites by bis-intercalators induces topological changes with potent antitumor effects

Nucleic acids research 2024年第15期52卷 9303-9316页

作者： Shih-Chun Huang Chia-Wei Chen Roshan Satange Chang-Chih Hsieh Chih-Chun Chang Shun-Ching Wang Chi-Li Peng Tai-Lin Chen Ming-Hsi Chiang Yih-Chern Horng Ming-Hon Hou Doctoral Program in Medical Biotechnology National Chung Hsing University Taichung 402 Taiwan. Graduate Institute of Genomics and Bioinformatics National Chung Hsing University Taichung 402 Taiwan. Department of Chemistry National Changhua University of Education Changhua 50058 Taiwan. Institute of Chemistry Academia Sinica Taipei 11528 Taiwan. Graduate Institute of Biotechnology National Chung Hsing University Taichung 402 Taiwan. Post Baccalaureate Medicine School of Medicine National Chung Hsing University Taichung 402 Taiwan. Biotechnology Center National Chung Hsing University Taichung 402 Taiwan.

Targeting inter-duplex junctions in catenated DNA with bidirectional bis-intercalators is a potential strategy for enhancing anticancer effects. In this study, we used d(CGTATACG)2, which forms a tetraplex base-pair junction that resembles the DNA-DNA contact structure, as a model target for two alkyl-linked diaminoacridine bis-intercalators, DA4 and DA5. Cross-linking of the junction site by the bis-intercalators induced substantial structural changes in the DNA, transforming it from a B-form helical end-to-end junction to an over-wounded side-by-side inter-duplex conformation with A-DNA characteristics and curvature. These structural perturbations facilitated the angled intercalation of DA4 and DA5 with propeller geometry into two adjacent duplexes. The addition of a single carbon to the DA5 linker caused a bend that aligned its chromophores with CpG sites, enabling continuous stacking and specific water-mediated interactions at the inter-duplex contacts. Furthermore, we have shown that the different topological changes induced by DA4 and DA5 lead to the inhibition of topoisomerase 2 activities, which may account for their antitumor effects. Thus, this study lays the foundations for bis-intercalators targeting biologically relevant DNA-DNA contact structures for anticancer drug development.

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Database Design for Pre-Eclampsia Case Administration

Database Design for Pre-Eclampsia Case Administration

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Information Technology and Digital Applications (ICITDA), IEEE International Conference on

作者： Faisal Asadi Gregorius Natanael Elwirehardja Joko Pebrianto Trinugroho Reza Rahutomo Bens Pardamean Computer Science Department School of Computer Science Bina Nusantara University Jakarta Indonesia Bioinformatics and Data Science Research Center Bina Nusantara University Jakarta Indonesia Information System Department School of Information Systems Bina Nusantara University Jakarta Indonesia Computer Science Department BINUS Graduate Program Master of Computer Science Bina Nusantara University Jakarta Indonesia

The Ministry of Health of Indonesia has referred to pre-eclampsia as one of the most severe diseases affecting women. As an urgency, it is crucial to administrate pre-eclampsia cases for disease prevention as a long-term national healthcare strategy. Regarding health science, case data was significant in developing research and innovation. However, the main problem regarding pre-eclampsia case administration is data handling, recording, and management incompetence. Hence, this research proposed a conceptual design of a database for pre-eclampsia case administration. The proposed design covered conceptual, logical, and physical design. We elaborate the concept into three concepts of pre-eclampsia disease: pre-treatment, treatment, and post-treatment. This study proposed a solution to gain more data and study pre-eclampsia disease in Indonesia.

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Identification of Meteorological Parameters Affecting Dengue Hemorrhagic Fever Incidences

Identification of Meteorological Parameters Affecting Dengue...

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International Conference on Informatics, Multimedia, Cyber and Information System (ICIMCIS)

作者： Faisal Asadi Joko Pebrianto Trinugroho Alam Ahmad Hidayat Reza Rahutomo Bens Pardamean Bioinformatics and Data Science Research Center Bina Nusantara University Jakarta Indonesia Information System Department School of Information Systems Bina Nusantara University Jakarta Indonesia Computer Science Department BINUS Graduate Program Master of Computer Science Bina Nusantara University Jakarta Indonesia

ISBN: (纸本)9781665473286

Tropical disease is one of the infectious diseases that affect Indonesia. Many people die because of tropical diseases, such as dengue hemorrhagic fever (DHF), chikungunya, leprosy, lymphatic, and filariasis. The Indonesian government's lack of public policy is the main problem in treating and preventing tropical diseases. The paper aims to describe the analysis results of the incidence of DHF in Jakarta, Indonesia. The analysis used the DHF incidences data from the Jakarta Health service surveillance office representative and combined it with the meteorological parameters data. The meteorological parameters were collected from the Bureau of Meteorological Climatology and Geophysics (BMKG). The statistical analysis of this research used Pearson's correlation. The results show that the meteorological parameters affecting DHF incidences are temperature, humidity, and wind speed.

关键词： Correlation Statistical analysis Wind speed Surveillance Multimedia systems Sociology Humidity

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Machine Learning Implementations in Childhood Stunting Research: A Systematic Literature Review

Machine Learning Implementations in Childhood Stunting Resea...

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International Conference on Information Management and Technology (ICIMTech)

作者： Reza Rahutomo Gregorius Natanael Elwirehardja Mahmud Isnan Faisal Asadi Bens Pardamean Information Systems Department School of Information Systems Bina Nusantara University Jakarta Indonesia Computer Science Department School of Computer Science Bina Nusantara University Jakarta Indonesia Bioinformatics and Data Science Research Center Bina Nusantara University Jakarta Indonesia Computer Science Department BINUS Graduate Program - Master of Computer Science Bina Nusantara University Jakarta Indonesia

Childhood stunting is a condition anticipated to affect the growth potential of children under the age of five. With numerous stunting researches that have been conducted, stunting datasets are now widely available to facilitate stunting research. This provides an opportunity to implement machine learning (ML) principles to produce a broader insight or a novel technique in stunting prediction. A systematic literature review is necessary to discover the landscape of machine learning implementation in the application domain as a preliminary study for creating an effective research roadmap. This paper presents a systematic literature review (SLR) of 22 curated manuscripts that focuses on identifying the ML models applied in stunting research, as well as the datasets used in such studies that were published during 2017–2022. The SLR process found that ML principles have been applied in stunting research since 2017, and the diversity of ML implementation has become more varied in 2021–2022. In terms of ML models, XGBoost and Random Forest are recognized as the two most utilized models, and stunting prediction is the most common ML implementation. The majority of stunting research utilizing ML has been conducted in Indonesia. Although national survey data has been the most commonly utilized dataset in stunting research, researchers in Indonesia have shown a preference for utilizing data from regional or independent surveys. This study will be followed by developing a classifier model for stunted children using XGBoost and Random Forest algorithms. The model will be trained on a dataset generated from StuntingDB.

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The Technology Behind Genomic Database

The Technology Behind Genomic Database

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International Conference on Cybernetics and Intelligent System (ICORIS)

作者： Joko Pebrianto Trinugroho Anzaludin Samsinga Perbangsa Bens Pardamean Bioinformatics and Data Science Research Center Bina Nusantara University Jakarta Indonesia Information Systems Department School of Information Systems Bina Nusantara University Jakarta Indonesia Computer Science Department BINUS Graduate Program - Master of Computer Science Bina Nusantara University Jakarta Indonesia

ISBN: (纸本)9781665453967

In this digital era, we are exposed to a large amount of data. This includes biological data, which stores information about living organisms, including Deoxyribonucleic acid (DNA), genes, and proteins. With the development of information technology and information system, most of available biological data are stored in an online public database. Many of the databases are free-access and easily used, which helps the users, especially researchers, to make use of the data. Among the known public biological databases are the University of California Santa Cruz (UCSC) Genome Browser Database and the Rat Genome Database (RGD). These two databases provide access to the biological data from different organisms. This paper aims to describe the technology of public biological databases. Also elucidated in this paper are the differences features between UCSC Genome Browser Database and the RGD. Our results showed that the UCSC contains much more biological data and features than the RGD. However, the genome browser of UCSC has a complex display, while the RGD has a simple display. Overall, both databases give the users the option to choose the most suitable database for them.

关键词： Proteins Databases Genomics DNA Rats Biology Organisms

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IoT for Water Quality Categorization

IoT for Water Quality Categorization

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International Conference on Cybernetics and Intelligent System (ICORIS)

作者： Hermantoro Sastrohartono Andreas Wahyu Krisdiarto Arief Ika Uktoro Reza Rahutomo Teddy Suparyanto Bens Pardamean Agricultural Engineering Department Faculty of Agricultural Technology Institute of Agriculture STIPER Yogyakarta Indonesia Information System Department School of Information Systems Bina Nusantara University Jakarta Indonesia Bioinformatics & Data Science Research Center Bina Nusantara University Jakarta Indonesia Computer Science Department BINUS Graduate Program Master of Computer Science Bina Nusantara University Jakarta Indonesia

In agricultural water research, the adoption of Internet of Things (IoT) technology has emerged as a pivotal approach for large-scale data collection. Water availability in the context of water quality is very important, both for domestic and industrial purposes. For domestic purposes, drinking water and bathing water are separated. Meanwhile, for the palm oil industry, boiler filler is differentiated from additional process water (dilution water). Water quality parameters can be assessed from turbidity and Total Dissolve Solid (TDS). Measurements using measuring instruments separately and repeatedly require significant energy, time, and costs. This research was conducted with the primary objective of presenting a novel method for categorizing water quality with the approach of IoT sensor technology. The research methodology entailed the utilization of an integrated IoT water sensors system in conjunction with manual water categorization. The methods consist of (1) system design, (2) design and installation of sensor and IoT-based microcontrollers, and (3) accuracy and precision testing compared with laboratory measurements. The precision of the integrated IoT water sensors was assessed through a dedicated sensor precision test, resulting in an accuracy rate of 94.4% for the turbidity sensor and 97.5% for the TDS sensor. Notably, this approach successfully discriminated drinking water with valid categorization, while other water types, including groundwater, water with tea, and water with coffee, yielded null categorization results.

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Inhibition of ADAM9 promotes the selective degradation of KRAS and sensitizes pancreatic cancers to chemotherapy

Nature Cancer

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Nature Cancer 2024年第3期5卷 400-419页

作者： Huang, Yu-Kai Cheng, Wei-Chung Kuo, Ting-Ting Yang, Juan-Cheng Wu, Yang-Chang Wu, Heng-Hsiung Lo, Chia-Chien Hsieh, Chih-Ying Wong, Sze-Ching Lu, Chih-Hao Wu, Wan-Ling Liu, Shih-Jen Li, Yi-Chuan Lin, Ching-Chan Shen, Chia-Ning Hung, Mien-Chie Lin, Jaw-Town Yeh, Chun-Chieh Sher, Yuh-Pyng Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan Cancer Biology and Precision Therapeutics Center China Medical University Taichung Taiwan Ph.D. Program for Cancer Biology and Drug Discovery China Medical University and Academia Sinica Taichung Taiwan School of Chinese Medicine College of Chinese Medicine China Medical University Taichung Taiwan Graduate Institute of Integrated Medicine College of Chinese Medicine China Medical University Taichung Taiwan Department of Medical Laboratory Science and Biotechnology College of Medical and Health Science Asia University Taichung Taiwan Center for Molecular Medicine China Medical University Hospital Taichung Taiwan Institute of Bioinformatics and Systems Biology National Yang Ming Chiao Tung University Taipei Taiwan National Institute of Infectious Diseases and Vaccinology National Health Research Institutes Miaoli Taiwan Graduate Institute of Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan Department of Biological Science and Technology China Medical University Taichung Taiwan Division of Hematology and Oncology China Medical University Hospital Taichung Taiwan Genomics Research Center Academia Sinica Taipei Taiwan Division of Gastroenterology and Hepatology Department of Internal Medicine E-Da Hospital Kaohsiung Taiwan Department of Medicine School of Medicine China Medical University Taichung Taiwan Department of Surgery Organ Transplantation Center China Medical University Hospital Taichung Taiwan Institute of Biochemistry and Molecular Biology China Medical University Taichung Taiwan

Kirsten rat sarcoma virus (KRAS) signaling drives pancreatic ductal adenocarcinoma (PDAC) malignancy, which is an unmet clinical need. Here, we identify a disintegrin and metalloproteinase domain (ADAM)9 as a modulator of PDAC progression via stabilization of wild-type and mutant KRAS proteins. Mechanistically, ADAM9 loss increases the interaction of KRAS with plasminogen activator inhibitor 1 (PAI-1), which functions as a selective autophagy receptor in conjunction with light chain 3 (LC3), triggering lysosomal degradation of KRAS. Suppression of ADAM9 by a small-molecule inhibitor restricts disease progression in spontaneous models, and combination with gemcitabine elicits dramatic regression of patient-derived tumors. Our findings provide a promising strategy to target the KRAS signaling cascade and demonstrate a potential modality to enhance sensitivity to chemotherapy in PDAC. © The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.

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Dual-targeting compounds possessing enhanced anticancer activity via microtubule disruption and histone deacetylase inhibition

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European Journal of Medicinal Chemistry 2024年 265卷 116042页

作者： Tseng, Yu-Wei Yang, Tsung-Jung Hsu, Yuan-Ling Liu, Jyung-Hurng Tseng, Yin-Chen Hsu, Tse-Wei Lu, Yueh Pan, Szu-Hua Cheng, Ting-Jen Rachel Fang, Jim-Min Department of Chemistry National Taiwan University Taipei 106 Taiwan Graduate Institute of Medical Genomics and Proteomics College of Medicine National Taiwan University Taipei 100 Taiwan Graduate Institute of Genomics and Bioinformatics College of Life Sciences National Chung Hsing University Taichung 40227 Taiwan The Genomics Research Center Academia Sinica Taipei 115 Taiwan Doctoral Degree Program of Translational Medicine National Taiwan University Taipei 100 Taiwan Genome and Systems Biology Degree Program National Taiwan University and Academia Sinica Taipei 100 Taiwan

Dual-targeting anticancer agents 4–29 are designed by combining the structural features of purine-type microtubule-disrupting compounds and HDAC inhibitors. A library of the conjugate compounds connected by appropriate linkers was synthesized and found to possess HDACs inhibitory activity and render microtubule fragmentation by activating katanin, a microtubule-severing protein. Among various zinc-binding groups, hydroxamic acid shows the highest inhibitory activity of Class I HDACs, which was also reconfirmed by three-dimensional quantitative structure-activity relationship (3D-QSAR) pharmacophore prediction. The purine–hydroxamate conjugates exhibit enhanced cytotoxicity against MDA-MB231 breast cancer cells, H1975 lung cancer cells, and various clinical isolated non-small-cell lung cancer cells with different epidermal growth factor receptor (EGFR) status. Pyridyl substituents could be used to replace the C2 and N9 phenyl moieties in the purine-type scaffold, which can help to improve the solubility under physiological conditions, thus increasing cytotoxicity. In mice treated with the purine–hydroxamate conjugates, the tumor growth rate was significantly reduced without causing toxic effects. Our study demonstrates the potential of the dual-targeting purine–hydroxamate compounds for cancer monotherapy. © 2023 Elsevier Masson SAS

关键词： Breast cancer Histidine deacetylase Hydroxamate Katanin Lung cancer Microtubule Purine-type conjugate

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Correction to: Droplet Hi-C enables scalable, single-cell profiling of chromatin architecture in heterogeneous tissues (Nature Biotechnology, (2024), 10.1038/s41587-024-02447-1)

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Nature Biotechnology 2025年

作者： Chang, Lei Xie, Yang Taylor, Brett Wang, Zhaoning Sun, Jiachen Armand, Ethan J. Mishra, Shreya Xu, Jie Tastemel, Melodi Lie, Audrey Gibbs, Zane A. Indralingam, Hannah S. Tan, Tuyet M. Bejar, Rafael Chen, Clark C. Furnari, Frank B. Hu, Ming Ren, Bing Department of Cellular and Molecular Medicine University of California San Diego La JollaCA United States Biomedical Sciences Graduate Program University of California San Diego La JollaCA United States Medical Scientist Training Program University of California San Diego La JollaCA United States Department of Quantitative Health Sciences Lerner Research Institute Cleveland Clinic Foundation ClevelandOH United States Systems Biology and Bioinformatics PhD Program Case Western Reserve University School of Medicine ClevelandOH United States Bioinformatics and Systems Biology Program University of California San Diego La JollaCA United States Moores Cancer Center UC San Diego La JollaCA United States Department of Neurosurgery University of Minnesota MinneapolisMN United States Department of Medicine University of California San Diego School of Medicine La JollaCA United States Center for Epigenomics Institute for Genomic Medicine School of Medicine University of California San Diego La JollaCA United States

Correction to: Nature Biotechnologyhttps://***/10.1038/s41587-024-02447-1, published online 18 October 2024. In the version of the article initially published, in the Methods section, both mentions of "MboII" should have read "MboI (NEB, R0147M)" and have now been corrected in the HTML and PDF versions of the article. © The Author(s) 2025.

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Genome data mining approach to identify potential protein in crop plants

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AIP Conference Proceedings 2024年第1期3026卷

作者： Joko Pebrianto Trinugroho Faisal Asadi Bens Pardamean Bioinformatics & Data Science Research Center Bina Nusantara University Jakarta Indonesia 11480 Computer Science Department BINUS Graduate Program - Master of Computer Science Program Bina Nusantara University Jakarta Indonesia 11480

There is a need to produce more crop plants to meet the future global demand. However, the climate change has affected the global crop yield. Consequently, finding an alternative approach to improve crop yield becomes essential. The development of sequencing techniques, as well as information technologies, have enabled us to perform genome data mining. Using genome data mining approach, it is possible to identify or discover a protein which has a particular characteristic. This study aims to identify a protein, which could potentially improve crop yield, using genome data mining approach. D1 protein was used as the target, as this protein is highly involved in photosynthesis. Then, protein sequences of various crop plants were collected from biological database. After conducting data trimming and filtering, sequence analysis was performed. The analysis was used to construct phylogenetic tree and create a 3D protein model. Sequence analysis displayed variation in amino acid sequence in D1 protein. Protein modelling located the variations, which scattered within D1 protein. Furthermore, we highlighted the amino acid residues that are the targets for genetic engineering. The research findings may provide a reference to improve crop production through genome mining approach.

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