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Annual international Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)

作者： Sheau-Ling Hsieh Yung-Ching Weng Chi-Huang Chen Kai-Ping Hsu Jeng-Wei Lin Feipei Lai EECS International Graduate Program Institute IT Center National Chiao Tung University Hsinchu Taiwan Taiwan University Taipei Taiwan Department of Electrical Engineering National Taiwan University Taipei Taiwan Computer and Information Networking Center National Taiwan University Taipei Taiwan Department of Information Management Tunghai University Taichung Taiwan Graduate Institute of Biomedical Electronics and Bioinformatics National Taiwan University Taipei Taiwan

The paper addresses Medical Hand Drawing Management System architecture and implementation. In the system, we developed four modules: hand drawing management module; patient medical records query module; hand drawing editing and upload module; hand drawing query module. The system adapts windows-based applications and encompasses web pages by *** hosting mechanism under web services platforms. The hand drawings implemented as files are stored in a FTP server. The file names with associated data, e.g. patient identification, drawing physician, access rights, etc. are reposited in a database. The modules can be conveniently embedded, integrated into any system. Therefore, the system possesses the hand drawing features to support daily medical operations, effectively improve healthcare qualities as well. Moreover, the system includes the printing capability to achieve a complete, computerized medical document process. In summary, the system allows web-based applications to facilitate the graphic processes for healthcare operations.

关键词： Medical services Biomedical imaging Printing Conferences Web services Graphics Databases

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Annual international Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)

作者： Chi-Huang Chen Sheau-Ling Hsieh Yung-Ching Weng Wen-Yung Chang Feipei Lai Department of Electrical Engineering National Taiwan University Taipei Taiwan EECS International Graduate Program Institute IT Center National Chiao Tung University Hsinchu Taiwan Department of Computer Science and Engineering National Taiwan University Taiwan Institute of Computer Science and Engineering College of Computer Science National Chiao Tung University Taiwan Graduate Institute of Biomedical Electronics and Bioinformatics National Taiwan University Taiwan

Semantic similarity measure plays an essential role in Information Retrieval and Natural Language Processing. In this paper we propose a page-count-based semantic similarity measure and apply it in biomedical domains. Previous researches in semantic web related applications have deployed various semantic similarity measures. Despite the usefulness of the measurements in those applications, measuring semantic similarity between two terms remains a challenge task. The proposed method exploits page counts returned by the Web Search Engine. We define various similarity scores for two given terms P and Q, using the page counts for querying P, Q and P AND Q. Moreover, we propose a novel approach to compute semantic similarity using lexico-syntactic patterns with page counts. These different similarity scores are integrated adapting support vector machines, to leverage the robustness of semantic similarity measures. Experimental results on two datasets achieve correlation coefficients of 0.798 on the dataset provided by A. Hliaoutakis, 0.705 on the dataset provide by T. Pedersen with physician scores and 0.496 on the dataset provided by T. Pedersen et al. with expert scores.

关键词： Semantics Biomedical measurements Correlation Kernel Training Medical services Support vector machine classification

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Predicting drug response through tumor deconvolution by cancer cell lines

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Patterns 2024年第4期5卷 100949页

作者： Hsu, Yu-Ching Chiu, Yu-Chiao Lu, Tzu-Pin Hsiao, Tzu-Hung Chen, Yidong Bioinformatics Program Taiwan International Graduate Program National Taiwan University Taipei115 Taiwan Bioinformatics Program Institute of Statistical Science Taiwan International Graduate Program Academia Sinica Taipei115 Taiwan Institute of Health Data Analytics and Statistics Department of Public Health College of Public Health National Taiwan University Taipei100 Taiwan Greehey Children's Cancer Research Institute University of Texas Health San Antonio San AntonioTX78229 United States Department of Medicine School of Medicine University of Pittsburgh PittsburghPA15261 United States UPMC Hillman Cancer Center University of Pittsburgh PittsburghPA15232 United States Department of Medical Research Taichung Veterans General Hospital Taichung40705 Taiwan Department of Population Health Sciences University of Texas Health San Antonio San AntonioTX78229 United States

Large-scale cancer drug sensitivity data have become available for a collection of cancer cell lines, but only limited drug response data from patients are available. Bridging the gap in pharmacogenomics knowledge between in vitro and in vivo datasets remains challenging. In this study, we trained a deep learning model, Scaden-CA, for deconvoluting tumor data into proportions of cancer-type-specific cell lines. Then, we developed a drug response prediction method using the deconvoluted proportions and the drug sensitivity data from cell lines. The Scaden-CA model showed excellent performance in terms of concordance correlation coefficients (>0.9 for model testing) and the correctly deconvoluted rate (>70% across most cancers) for model validation using Cancer Cell Line Encyclopedia (CCLE) bulk RNA data. We applied the model to tumors in The Cancer Genome Atlas (TCGA) dataset and examined associations between predicted cell viability and mutation status or gene expression levels to understand underlying mechanisms of potential value for drug repurposing. © 2024 The Authors

关键词： Tumors

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Revised JNLPBA corpus: A revised version of biomedical NER corpus for relation extraction task

arXiv

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arXiv 2019年

作者： Huang, Ming-Siang Lai, Po-Ting Tsai, Richard Tzong-Han Hsu, Wen-Lian Bioinformatics Program Taiwan International Graduate Program Institute of Information Science Academia Sinica Taipei Taiwan Institute of Biomedical Informatics National Yang Ming University Taipei Taiwan Department of Computer Science National Tsing-Hua University Hsinchu Taiwan Intelligent Agent Systems Laboratory Institute of Information Science Academia Sinica Taipei Taiwan Intelligent Information Service Research Laboratory Department of Computer Science and Information Engineering National Central University Taoyuan Taiwan

The advancement of biomedical named entity recognition (BNER) and biomedical relation extraction (BRE) researches promotes the development of text mining in biological domains. As a cornerstone of BRE, robust BNER system is required to identify the mentioned NEs in plain texts for further relation extraction stage. However, the current BNER corpora, which play important roles in these tasks, paid less attention to achieve the criteria for BRE task. In this study, we present Revised JNLPBA corpus, the revision of JNLPBA corpus, to broaden the applicability of a NER corpus from BNER to BRE task. We preserve the original entity types including protein, DNA, RNA, cell line and cell type while all the abstracts in JNLPBA corpus are manually curated by domain experts again basis on the new annotation guideline focusing on the specific NEs instead of general terms. Simultaneously, several imperfection issues in JNLPBA are pointed out and made up in the new corpus. To compare the adaptability of different NER systems in Revised JNLPBA and JNLPBA corpora, the F1-measure was measured in three open sources NER systems including BANNER, Gimli and NERSuite. In the same circumstance, all the systems perform average 10% better in Revised JNLPBA than in JNLPBA. Moreover, the cross-validation test is carried out which we train the NER systems on JNLPBA/Revised JNLPBA corpora and access the performance in both protein-protein interaction extraction (PPIE) and biomedical event extraction (BEE) corpora to confirm that the newly refined Revised JNLPBA is a competent NER corpus in biomedical relation application. The revised JNLPBA corpus is freely available at ***/BNER/Content/Revised_***. Copyright © 2019, The Authors. All rights reserved.

关键词： Proteins

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Development of label-free triboelectric nanosensors as screening platforms for anti-tumor drugs

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Nano Energy 2024年 125卷

作者： Cheng, Yu-Ying Ganguly, Anindita Cheng, Yi-Yun Ortiz, Christopher Llynard D. Pal, Arnab Shah, Pramod Kaswan, Kuldeep Yang, Lee-Wei Lin, Zong-Hong Department of Biomedical Engineering National Taiwan University Taipei10617 Taiwan Institute of Biomedical Engineering National Tsing Hua University Hsinchu30013 Taiwan Internet of Senses Research Center National Tsing Hua University Hsinchu30013 Taiwan Praexisio Taiwan Inc. New Taipei221425 Taiwan Institute of Bioinformatics and Structural Biology National Tsing Hua University Hsinchu300044 Taiwan Chemical Biology and Molecular Biophysics Program Taiwan International Graduate Program Institute of Biological Chemistry Academia Sinica Taipei115 Taiwan Department of Chemistry National Tsing Hua University Hsinchu300044 Taiwan International Intercollegiate PhD Program National Tsing Hua University Hsinchu300044 Taiwan Department of Power Mechanical Engineering National Tsing Hua University Hsinchu300044 Taiwan Biomedical Artificial Intelligence PhD Program National Tsing Hua University Hsinchu300044 Taiwan Physics Division National Center for Theoretical Sciences Taipei Taiwan

This study introduces a general label-free drug screening platform with potential to support high-throughput drug screening for any protein target. Its innovation lies in quantifying the affinity of molecule-molecule interactions via voltage output variation, which achieves unprecedented selectivity and sensitivity. It combines computational analysis complemented by experimental substantiation with a solid-liquid triboelectric nanosensor. Owing to its high binding affinity, FKBP-rapamycin is used as a model system to demonstrate the platform's sensitivity. Subsequently, the research is extended to study drug interactions with an oncogenic protein ATG4B. The findings unveil the binding of S130 and Tioconazole to ATG4B, a critical cysteine protease involved in autophagy, while revealing that Dexamethasone does not bind ATG4B. This binding exerts a specific inhibitory effect on autophagic flux and triggers cancer cell apoptosis. The results support the previously verified inhibitory effects of these drugs and the effectiveness of a newly developed self-powered drug screening platform, leveraging the principles of solid-liquid contact electrification. This approach adeptly confronts enduring challenges in traditional drug development methods where biochemical assays need to be designed for each individual protein target or only time-consuming and concentration-demanding molecular interaction measurements were made available. © 2024 Elsevier Ltd

关键词： Nanosensors

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Structural insights into the role of N-terminal integrity in PhoSL for core-fucosylated N-glycan recognition

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international Journal of Biological Macromolecules 2024年 255卷 128309页

作者： Lou, Yuan-Chao Tu, Cheng-Fen Chou, Chun-Chi Yeh, Hsin-Hong Chien, Chia-Yu Sadotra, Sushant Chen, Chinpan Yang, Ruey-Bing Hsu, Chun-Hua Institute of Biomedical Sciences Academia Sinica Taipei115 Taiwan Department of Agricultural Chemistry National Taiwan University Taipei106 Taiwan Chemical Biology and Molecular Biophysics Taiwan International Graduate Program Academia Sinica Taipei115 Taiwan Institute of Bioinformatics and Structural Biology National Tsing Hua University Hsinchu300 Taiwan Biomedical Translation Research Center Academia Sinica Taipei115 Taiwan Ph.D. Program in Drug Discovery and Development Industry College of Pharmacy Taipei Medical University Taipei110 Taiwan Genome and Systems Biology Degree Program National Taiwan University and Academia Sinica Taipei106 Taiwan Institute of Biochemical Sciences National Taiwan University Taipei106 Taiwan Center for Computational and Systems Biology National Taiwan University Taipei106 Taiwan

PhoSL (Pholiota squarrosa Lectin) has an exceptional binding affinity for biomolecules with core-fucosylated N-glycans. This modification involves the addition of fucose to the inner N-acetylglucosamine within the N-glycan structure and is known to influence many physiological processes. Nevertheless, the molecular interactions underlying high-affinity binding of native PhoSL to core-fucosylated N-glycans remain largely unknown. In this study, we devised a strategy to produce PhoSL with the essential structural characteristics of the native protein (n-PhoSL). To do so, a fusion protein was expressed in E. coli and purified. Then, enzymatic cleavage and incubation with glutathione were utilized to recapitulate the native primary structure and disulfide bonding pattern. Subsequently, we identified the residues crucial for n-PhoSL binding to core-fucosylated chitobiose (N2F) via NMR spectroscopy. Additionally, crystal structures were solved for both apo n-PhoSL and its N2F complex. These analyses suggested a pivotal role of the N-terminal amine in maintaining the integrity of the binding pocket and actively contributing to core-fucose recognition. In support of this idea, the inclusion of additional residues at the N-terminus considerably reduced binding affinity and PhoSL cytotoxicity toward breast cancer cells. Taken together, these findings can facilitate the utilization of PhoSL in basic research, diagnostics and therapeutic strategies. © 2023 Elsevier B.V.

关键词： Proteins

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Improving quantitation accuracy in isobaric-labeling mass spectrometry experiments with spectral library searching and feature-based peptide-spectrum match filter

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Scientific Reports 2023年第1期13卷 1-10页

作者： Kuo, Tzu-Yun Wang, Jen-Hung Huang, Yung-Wen Sung, Ting-Yi Chen, Ching-Tai Department of Biochemical Science and Technology National Taiwan University Taipei 10617 Taiwan Bioinformatics Program Taiwan International Graduate Program Institute of Statistical Science Academia Sinica Taipei 11529 Taiwan Institute of Information Science Academia Sinica Taipei 11529 Taiwan Institute of Biomedical Informatics National Yang Ming Chiao Tung University Taipei 11221 Taiwan Department of Computer Science and Information Engineering National Taiwan University Taipei 10617 Taiwan Department of Bioinformatics and Biomedical Engineering Asia University Taichung 41354 Taiwan Center for Precision Health Research Asia University Taichung 41354 Taiwan

Isobaric labeling relative quantitation is one of the dominating proteomic quantitation technologies. Traditional quantitation pipelines for isobaric-labeled mass spectrometry data are based on sequence database searching. In this study, we present a novel quantitation pipeline that integrates sequence database searching, spectral library searching, and a feature-based peptide-spectrum-match (PSM) filter using various spectral features for filtering. The combined database and spectral library searching results in larger quantitation coverage, and the filter removes PSMs with larger quantitation errors, retaining those with higher quantitation accuracy. Quantitation results show that the proposed pipeline can improve the overall quantitation accuracy at the PSM and protein levels. To our knowledge, this is the first study that utilizes spectral library searching to improve isobaric labeling-based quantitation. For users to conveniently perform the proposed pipeline, we have implemented the feature-based filter being executable on both Windows and Linux platforms;its executable files, user manual, and sample data sets are freely available at https://***/comics/Software_*** . Furthermore, with the developed filter, the proposed pipeline is fully compatible with the Trans-Proteomic Pipeline. © 2023, Springer Nature Limited.

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Successive responses of three coral holobiont components (coral hosts, symbiotic algae, and bacteria) to daily temperature fluctuations

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Ecological Indicators 2024年 158卷

作者： Hsieh, Yunli Eric Lu, Chih-Ying Liu, Po-Yu Kao, Jia-Min Yang, Sung-Yin Wu, Chien-Yi Wong, Jing-Wen Michelle Shikina, Shinya Fan, Tung-Yung Yang, Shan-Hua Systems Biology and Mathematical Modelling group Max Planck Institute of Molecular Plant Physiology Potsdam Germany Institute of Biochemistry and Biology Bioinformatics Department University of Potsdam Potsdam Germany School of BioSciences The University of Melbourne ParkvilleVIC Australia Molecular and Biological Agricultural Sciences Program Taiwan International Graduate Program National Chung Hsing University and Academia Sinica Taipei Taiwan Graduate Institute of Biotechnology National Chung Hsing University Taichung Taiwan Biodiversity Research Center Academia Sinica Taipei Taiwan School of Medicine College of Medicine National Sun Yat-sen University Kaohsiung Taiwan Institute of Fisheries Science National Taiwan University Taipei Taiwan Department of Aquatic Bioscience National Chiayi University Chiayi Taiwan Institute of Marine Environment and Ecology National Taiwan Ocean University Keelung Taiwan National Museum of Marine Biology and Aquarium Pingtung Taiwan

Corals and their associated microbiota form a "holobiont," which includes symbiotic algae and other associated microbiota dominated by bacteria. The composition of holobiont is influenced by various environmental factors, such as increasing sea water temperatures. Previous studies of the effects of temperature changes on coral physiology and associated bacterial communities have been conducted based on stable water temperatures set by mean temperatures, or by slowly increasing/decreasing temperatures. However, the daily temperature fluctuations that corals experience in nature are not stable. The current understanding of the effects of large daily temperature fluctuations on coral and associated bacterial community dynamics is limited. Hence, we conducted a four-week tank experiment using different large daily temperature fluctuations (±5 °C and ±7 °C) accompanied by continuous warming conditions (26 °C to 29 °C) to investigate the effects on two common reef-building corals, Stylophora pistillata and Pocillopora acuta. During the experiment, the activity of coral host catalase and superoxide dismutase were measured, the photosynthetic ability of symbiotic algae was recorded, and the variation in bacterial communities was analyzed using the V6-V8 region of 16S rDNA. According to the results, different parts of the holobionts of two coral species exhibited varying response rates to the continuous warming conditions and diurnal temperature fluctuations. Additionally, it was found that diurnal temperature fluctuations may mitigate the heat stress on the host and reduce the changes in bacterial response to warming. Therefore, it is suggested that the holobionts of different coral species may adopt different adaptation and survival strategies in response to diurnal temperature fluctuations and warming. Finally, based on the response of these two coral species under the conditions of diurnal temperature fluctuations and continuous warming, Acinetobacter and Rhodobacteracea

关键词： Temperature distribution

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Glycans on influenza hemagglutinin affect receptor binding and immune response

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Proceedings of the National Academy of Sciences of the United States of America 2009年第43期106卷 18137-18142页

作者： Wang, Cheng-Chi Chen, Juine-Ruey Tseng, Yung-Chieh Hsu, Che-Hsiung Hung, Yu-Fu Chen, Shih-Wei Chen, Chin-Mei Khoo, Kay-Hooi Cheng, Ting-Jen Cheng, Yih-Shyun E. Jan, Jia-Tsrong Wu, Chung-Yi Ma, Che Wong, Chi-Huey Genomics Research Center Taipei 115 Taiwan Institute of Biochemical Sciences National Taiwan University Taipei 106 Taiwan Institute of Biochemistry and Molecular Biology National Yang-Ming University Taipei 112 Taiwan Chemical Biology and Molecular Biophysics Taiwan International Graduate Program Taipei 115 Taiwan Institute of Bioinformatics and Structural Biology National Tsing Hua University Hsinchu 300 Taiwan Institute of Biological Chemistry Academia Sinica Taipei 115 Taiwan

Recent cases of avian influenza H5N1 and the swine-origin 2009 H1N1 have caused a great concern that a global disaster like the 1918 influenza pandemic may occur again. Viral transmission begins with a critical interaction between hemagglutinin (HA) glycoprotein, which is on the viral coat of influenza, and sialic acid (SA) containing glycans, which are on the host cell surface. To elucidate the role of HA glycosylation in this important interaction, various defined HA glycoforms were prepared, and their binding affinity and specificity were studied by using a synthetic SA microarray. Truncation of the N-glycan structures on HA increased SA binding affinities while decreasing specificity toward disparate SA ligands. The contribution of each monosaccharide and sulfate group within SA ligand structures to HA binding energy was quantitatively dissected. It was found that the sulfate group adds nearly 100-fold (2.04 kcal/mol) in binding energy to fully glycosylated HA, and so does the biantennary glycan to the monoglycosylated HA glycoform. Antibodies raised against HA protein bearing only a single N-linked GlcNAc at each glycosylation site showed better binding affinity and neutralization activity against influenza subtypes than the fully glycosylated HAs elicited. Thus, removal of structurally nonessential glycans on viral surface glycoproteins may be a very effective and general approach for vaccine design against influenza and other human viruses.

关键词： Flu vaccine Glycan binding Glycosylation

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Phosphoproteomic analysis reveals distinctive responses in Mangrovibacter phragmatis under high-salinity condition

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Biochemical and biophysical research communications 2024年 736卷 150514页

作者： Hong Soon Chin Narendrakumar Ravi Varadharajulu Zhi-Han Lin Chuan-Chih Hsu Steve S-F Yu Institute of Chemistry Academia Sinica Taipei Taiwan Chemical Biology and Molecular Biophysics Program Taiwan International Graduate Program Academia Sinica Taipei Taiwan Institute of Bioinformatics and Structural Biology National Tsing Hua University Hsinchu Taiwan. Molecular Science and Technology Program Taiwan International Graduate Program Academia Sinica Taipei Taiwan Department of Chemistry National Tsing Hua University Hsinchu Taiwan. Institute of Biochemical Sciences National Taiwan University Taipei Taiwan. Institute of Plant and Microbial Biology Academia Sinica Taipei Taiwan. Molecular Science and Technology Program Taiwan International Graduate Program Academia Sinica Taipei Taiwan. Electronic address: sfyu@gate.sinica.edu.tw.

We conducted a thorough genome-wide investigation of protein phosphorylation in the halotolerant bacterium Mangrovibacter phragmitis (MPH) ASIOC01, using the Fe-IMAC enrichment method combined with tandem mass spectrometry under low- and high-salinity conditions. The phosphoproteome comprises 86 unique phosphorylated proteins, crucially involving pathways such as glycolysis/gluconeogenesis, the citrate cycle, chaperones, ribosomal proteins, and cell division. This study represents the first and most extensive investigation to-date comparing the bacterial phosphoproteome under different osmotic conditions using a gel-free approach. We identified 45 unique phosphoproteins in MPH cultured in media containing 1 % NaCl, and 33 exclusive phosphoproteins in MPH cultured in media containing 5 % NaCl. Eight phosphoproteins were detected in both growth conditions. Analysis of high-confidence phosphosites reveals that phosphorylation predominantly occurs on serine residues (52.3 %), followed by threonine (35.1 %) and tyrosine (12.6 %) residues. Interestingly, 34 % of the phosphopeptides display multiple phosphosites. Currently, prokaryotic phosphorylation site prediction platforms like MPSite and NetPhosBac 1.0 demonstrate an average prediction accuracy of only 21 % when applied to our dataset. Fourteen phosphoproteins did not yield matches when compared against dbPSP 2.0 (database of Phosphorylation Sites in Prokaryotes), indicating that these proteins may be novel phosphoproteins. These unique proteins undergoing phosphorylation under high salinity growth conditions potentially enhance their adaptive capabilities to environmental challenges.

关键词： Halotolerance LC-MS/MS Mangrovibacter phragmitis Osmotic-stress Phosphoproteomes Ser/thr/tyr phosphorylation

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