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1. List of contributors

Author

Aizawa, Shin-Ichi, primary, Alberdi, Pilar, additional, Alexander, David C., additional, Alía, Alberto, additional, Allison, D.G., additional, Amyes, Sebastian G.B., additional, An, Haoran, additional, Andrade, María J., additional, Antelmann, Haike, additional, Arias, Cesar A., additional, Asensio, Miguel A., additional, Axell-House, Dierdre B., additional, Bae, Hee-Won, additional, Baena, Laura Muñoz, additional, Baig, Abdul Mannan, additional, Bailey, Spenser O., additional, Baize, Sylvain, additional, Baldi, Pablo C., additional, Barbosa, Angela Silva, additional, Barbuddhe, Sukhadeo B., additional, Bard, Emilie, additional, Barry, Eileen M., additional, Basarab, Gregory S., additional, Beloborodova, N.V, additional, Bermúdez, Elena, additional, Bidmos, Fadil A., additional, Bisgaard, Magne, additional, Blakely, Garry W., additional, Bloch, Evan, additional, Boesen, Thias Oberg, additional, Bose, Dipayan, additional, Botero, Javier Enrique, additional, Bouabe, Hicham, additional, Bouchard, Michael J., additional, Bozue, Joel A., additional, Bradbury, Richard S., additional, Brett Moreau, G., additional, Cabezas-Cruz, Alejandro, additional, Cai, Rong-Jun, additional, Calderón, Enrique J., additional, Cao, Boyang, additional, Carmena, David, additional, Carvalho, Eneas, additional, Caulfield, Amanda D., additional, Cen, Shan, additional, Chai, Jong-Yil, additional, Chamberland, Robin R., additional, Champredon, David, additional, Chan, Edward D., additional, Charbon, Godefroid, additional, Chato, Connor, additional, Chelomina, G.N., additional, Chen, Jingyu, additional, Chen, Min, additional, Chen, Shuyu, additional, Chen, Suilin, additional, Chen, Yanfei, additional, Chen, Zhaoyuan, additional, Cheng, Aimin, additional, Cheng, Keding, additional, Chiu, Charles Y., additional, Cho, You-Hee, additional, Christensen, Henrik, additional, Chrtdernevskaya, E.A., additional, Contreras, Adolfo, additional, Contreras, Marinela, additional, Córdoba, Juan J., additional, Córdoba, María G., additional, Costa, Rita, additional, Cote, Christopher K., additional, Cui, Xiangling, additional, Cui, Yujun, additional, Dacal, Elena, additional, Dammann, Allison N., additional, Das, Shubhagata, additional, Dashti, Alejandro, additional, de la Fuente, José, additional, de la Garza, Mireya, additional, Delgado, Josué, additional, Delgado-Cuesta, Juan, additional, Deng, Haiteng, additional, Deng, Li, additional, Dey, Debajit, additional, Dhama, Kuldeep, additional, Diego, Juan García-Bernalt, additional, Ding, Hao, additional, Doern, Christopher D., additional, Dorman, Charles J., additional, Du, Zongmin, additional, Dunbar, Sherry A., additional, Duthie, Malcolm, additional, Dybvig, Kevin F., additional, Eakin, Ann E., additional, Eallonardo, Samuel J., additional, Eberly, Allison R., additional, Echeverry, Adriana Jaramillo, additional, Egland, Paul G., additional, El Zowalaty, Mohamed E., additional, Endsley, Janice Jones, additional, Eom, Keeseon S., additional, Evans, Benjamin A., additional, Falkinham, Joseph O., additional, Feng, Siwei, additional, Feng, Yaoyu, additional, Feng, Zongdi, additional, Fernández-Soto, Pedro, additional, Ferreira, Roux-Cil, additional, Flores-Huerta, Nadia, additional, Foster, Timothy J., additional, Fox-Moon, Sandra M., additional, Fraga, Tatiana Rodrigues, additional, Fredricks, David N., additional, Freitag, Nancy E., additional, Frimodt-Møller, Jakob, additional, Fuller, Risa, additional, Ganesh, Balasubramanian, additional, Gao, Ning, additional, García-Carnero, Laura C., additional, Garzetti, Debora, additional, Geoghegan, Joan A., additional, Ghenim, Raed, additional, Giambartolomei, Guillermo H., additional, Gilbert, Nicole M., additional, Gillis, Thomas Phillip, additional, Gladstone, Camilla A., additional, Gómez-Gaviria, Manuela, additional, Gómez-Marín, Jorge E., additional, Gong, Tengfang, additional, González, Ramón A., additional, Gray-Owen, Scott D., additional, Gu, Bing, additional, Guzmán-Téllez, Paula, additional, Hajal, Caroline, additional, Han, Yanping, additional, Hao, Yi, additional, Harrington, Amanda T., additional, Harris, Jason B., additional, Harvill, Eric T., additional, Hasan, S. Saif, additional, He, Guang-Jun, additional, He, Yongqun, additional, Heffron, Jared D., additional, Hidalgo, Paloma, additional, Hindiyeh, Musa Y., additional, Hreha, Teri N., additional, Hu, Xiaoyu, additional, Huang, Guanghua, additional, Huang, Jiangqing, additional, Huang, Liang, additional, Huang, Shifeng, additional, Huang, Xingxu, additional, Huang, Xueting, additional, Huang, Yilun, additional, Huffman, Anthony, additional, Humphreys, Tricia L., additional, Hunstad, David A., additional, Inglis, Timothy J.J., additional, Isaac, Lourdes, additional, Jacobs, Samantha E., additional, Janowicz, Diane M., additional, Jeon, Hyeong-Kyu, additional, Ji, Quanjiang, additional, Jia, Qi, additional, Jia, Wei, additional, Jin, Shouguang, additional, Jneidi, Lama, additional, Jose, Shinsmon, additional, Jung, Bong-Kwang, additional, Kattan, Randa, additional, Kaushik, Rahul, additional, Khare, Reeti, additional, Kim, Eun Sook, additional, Kirn, Thomas J., additional, Koo, Hyun, additional, Köster, Pamela C., additional, Krause, Peter J., additional, Kumar, Sanjai, additional, Kupz, Andreas, additional, Lambert, P.A., additional, Lamont, Richard J., additional, Langford, Paul R., additional, Lebeaux, David, additional, Legname, Giuseppe, additional, Li, Bin, additional, Li, Chunhao, additional, Li, Fen, additional, Li, Jun, additional, Li, Lanjuan, additional, Li, Ruofan, additional, Li, Ruoyu, additional, Li, Ting, additional, Li, Yang-Yang, additional, Li, Yanhua, additional, Li, Zhuorong, additional, Liang, Xiaomeng, additional, Liao, Guojian, additional, Lin, Ping, additional, Ling, Yun, additional, Liu, Bo, additional, Liu, Dongyou, additional, Liu, Guohua, additional, Liu, Huidi, additional, Liu, Jiafeng, additional, Liu, Jintao, additional, Liu, Qi, additional, Liu, Shu-Lin, additional, Liu, Taiping, additional, Liu, Tongbao, additional, Liu, Wei, additional, Liu, Yan, additional, Liu, Yanni, additional, Liu, Yisong, additional, Liu, Yuan, additional, Løbner-Olesen, Anders, additional, Loeffelholz, Michael, additional, Lu, Hongzhou, additional, Luna, Brian, additional, Ma, Bingting, additional, Ma, Chengying, additional, Ma, Shuang, additional, Ma, TianLi, additional, Madan, Rajat, additional, Mahle, Rachael E., additional, Mahlen, Steven D., additional, Malik, Satya Veer Singh, additional, Malik, Yashpal Singh, additional, Malvy, Denis, additional, Mann, Barbara J., additional, Marasini, Daya, additional, Maris, Alexander S., additional, Marjomäki, Varpu, additional, Marjuki, Henju, additional, Martín, Alberto, additional, Martín, Irene, additional, Martínez-Castillo, Moisés, additional, Martínez-Pabón, María Cecilia, additional, Mathison, Blaine A., additional, Ma’ayeh, Showgy, additional, McDowell, Andrew, additional, McLaughlin, Stephanie E., additional, McSheffrey, Gordon G., additional, Medrano, Francisco J., additional, Meehan, Conor J., additional, Mehta, Dhwani, additional, Mejía-Oquendo, Manuela, additional, Melo-Cristino, José, additional, Mendoza-Barberá, Elena, additional, Meng, Xinan, additional, Merino, Susana, additional, Merritt, Adam J., additional, Miller, Steve, additional, Miller, William R., additional, Minamino, Tohru, additional, Mirzaei, Mohammadali Khan, additional, Mora-Montes, Héctor M., additional, Mortensen, Joel, additional, Mostafa, Heba H., additional, Muhsen, Khitam, additional, Mujahed, Ahlam, additional, Muro, Antonio, additional, Murphy, Olwen C., additional, Newton, Hayley J., additional, Nguyen, April H., additional, Nichols, Wright W., additional, Niu, Siqiang, additional, Núñez, Félix, additional, Obregon, Dasiel, additional, Okamoto, Akira, additional, Okutani, Akiko, additional, Olabode, Abayomi, additional, Omar, Muna, additional, Ong, Edison, additional, Ouyang, Zhiming, additional, Pacak, Christina A., additional, Pacheco-Yépez, Judith, additional, Palmer, John, additional, Pang, Xiaoli, additional, Paredes-Sabja, Daniel, additional, Peng, Zhong, additional, Peng, Zonggen, additional, Pérez-Nevado, Francisco, additional, Poon, Art, additional, Pospíšilová, Petra, additional, Potts, Caelin C., additional, Pu, Qinqin, additional, Pujic, Petar, additional, Qi, Rui, additional, Qian, Chenyun, additional, Qian, Liu, additional, Qin, Aiping, additional, Qu, Fen, additional, Rakin, Alexander, additional, Ramesh, Ashwin, additional, Ramirez, Mario, additional, Rao, Yu, additional, Ratner, Adam J., additional, Rawool, Deepak B., additional, Rehman, Asma, additional, Ren, Jie, additional, Ren, Ping, additional, Retchless, Adam C., additional, Robertson, Erle S., additional, Rodríguez, Alicia, additional, Rodriguez, Azucena, additional, Rodríguez-Medina, Carolina, additional, Rodriguez-Nava, Veronica, additional, Rohde, Manfred, additional, Romero-Rodríguez, Alba, additional, Rosales-Morgan, Gabriela, additional, Rosenkranz, Andrea L., additional, Ruiz-Moyano, Santiago, additional, Ruokolainen, Visa, additional, Sabateen, Ali, additional, Sahu, Radhakrishna, additional, Sails, Andrew, additional, Sang, Yu, additional, Santana, Clarissa H., additional, Santos, Jesus A., additional, Santos, Renato L., additional, Schmitz, Jonathan E., additional, Serrano-Luna, Jesús, additional, Shen, Jianzhong, additional, Shen, Zhangqi, additional, Shibayama, Mineko, additional, Shirtliff, Mark E., additional, Silva-Costa, Catarina, additional, Silva-Olivares, Angélica, additional, Singh, Niraj Kumar, additional, Šmajs, David, additional, Smith, Robert P., additional, Smith, Sophie, additional, Snyder, Lori A.S., additional, Song, Yinggai, additional, Soro, Aurea Simon, additional, Spearman, Paul, additional, Spellberg, Brad, additional, Sprague, Lisa D., additional, Stratton, Charles W., additional, Strenk, Susan M., additional, Strugnell, Richard A., additional, Sun, Keer, additional, Suo, Xun, additional, Suzuki-Hatano, Silveli, additional, Svärd, Staffan, additional, Talbot, Elizabeth A., additional, Tamez-Castrellón, Alma K., additional, Tan, Nie, additional, Tang, Cynthia Y., additional, Tang, Yi-Wei, additional, Tao, Jia, additional, Tao, Lili, additional, Terrero-Salcedo, David, additional, Tharmalingam, Jayaraman, additional, Thwe, Phyu M., additional, Tiamani, Kawtar, additional, Tomás, Juan M., additional, Topaz, Nadav, additional, Tsai, Ang-Chen, additional, Tsalik, Ephraim L., additional, Tuomanen, Elaine I., additional, Turenne, Christine Y., additional, Tyagi, Anuj, additional, Uprety, Priyanka, additional, Valour, Florent, additional, van Hensbergen, Vincent P., additional, Venkatesan, Arun, additional, Vergis, Jess, additional, Villar, Margarita, additional, Vollmer, Waldemar, additional, Waites, Ken B., additional, Wan, Xiu-Feng, additional, Wang, Guiqing, additional, Wang, Lijun, additional, Wang, Lin, additional, Wang, Linqi, additional, Wang, Xiangru, additional, Wang, Xin, additional, Wang, Xinjie, additional, Wang, Ya-Ting, additional, Wang, Yang, additional, Wang, Yating, additional, Weil, Ana A., additional, Welkos, Susan L., additional, Wengenack, Nancy L., additional, Westblade, Lars F., additional, Whitfield, Chris, additional, Wu, Hui, additional, Wu, Lijuan, additional, Wu, Min, additional, Wu, Yarong, additional, Wu, Zhaowei, additional, Xiang, Ye, additional, Xiao, Di, additional, Xiao, Li, additional, Xiao, Lihua, additional, Xu, Tao, additional, Xu, Wenyue, additional, Xu, Xinping, additional, Xue, Jinling, additional, Yadav, Jay Prakash, additional, Yan, Junxiang, additional, Yan, Yixin, additional, Yang, Changmei, additional, Yang, Ruifu, additional, Yang, Ying, additional, Yao, Kaihu, additional, Yao, Yu-Feng, additional, Yeakle, Kyle C., additional, Yu, Demin, additional, Yu, Hao, additional, Yu, Xue-Jie, additional, Yuan, Zhenghong, additional, Zai, Wenjing, additional, Zhang, Jianzhong, additional, Zhang, Jing-Ren, additional, Zhang, Lanyue, additional, Zhang, Lijie, additional, Zhang, Qiwei, additional, Zhang, Wenbao, additional, Zhang, Wenhong, additional, Zhang, Xinxin, additional, Zhao, Youbao, additional, Zhou, Chuanmin, additional, Zhu, Feng, additional, Zhu, Jingting, additional, and Zhu, Yongqun, additional

Published
2024
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3. Ontology-based systematic classification and analysis of coronaviruses, hosts, and host-coronavirus interactions towards deep understanding of COVID-19

Author

Yu, Hong, Li, Li, Huang, Hsin-hui, Wang, Yang, Liu, Yingtong, Ong, Edison, Huffman, Anthony, Zeng, Tao, Zhang, Jingsong, Li, Pengpai, Liu, Zhiping, Zhang, Xiangyan, Ye, Xianwei, Handelman, Samuel K., Higgins, Gerry, Omenn, Gilbert S., Athey, Brian, Hur, Junguk, Chen, Luonan, and He, Yongqun

Subjects
Quantitative Biology - Other Quantitative Biology
Abstract

Given the existing COVID-19 pandemic worldwide, it is critical to systematically study the interactions between hosts and coronaviruses including SARS-Cov, MERS-Cov, and SARS-CoV-2 (cause of COVID-19). We first created four host-pathogen interaction (HPI)-Outcome postulates, and generated a HPI-Outcome model as the basis for understanding host-coronavirus interactions (HCI) and their relations with the disease outcomes. We hypothesized that ontology can be used as an integrative platform to classify and analyze HCI and disease outcomes. Accordingly, we annotated and categorized different coronaviruses, hosts, and phenotypes using ontologies and identified their relations. Various COVID-19 phenotypes are hypothesized to be caused by the backend HCI mechanisms. To further identify the causal HCI-outcome relations, we collected 35 experimentally-verified HCI protein-protein interactions (PPIs), and applied literature mining to identify additional host PPIs in response to coronavirus infections. The results were formulated in a logical ontology representation for integrative HCI-outcome understanding. Using known PPIs as baits, we also developed and applied a domain-inferred prediction method to predict new PPIs and identified their pathological targets on multiple organs. Overall, our proposed ontology-based integrative framework combined with computational predictions can be used to support fundamental understanding of the intricate interactions between human patients and coronaviruses (including SARS-CoV-2) and their association with various disease outcomes., Comment: 32 pages, 1 table, 6 figures

Published
2020

4. Modelling kidney disease using ontology: insights from the Kidney Precision Medicine Project

Author

Ong, Edison, Wang, Lucy L, Schaub, Jennifer, O’Toole, John F, Steck, Becky, Rosenberg, Avi Z, Dowd, Frederick, Hansen, Jens, Barisoni, Laura, Jain, Sanjay, de Boer, Ian H, Valerius, M Todd, Waikar, Sushrut S, Park, Christopher, Crawford, Dana C, Alexandrov, Theodore, Anderton, Christopher R, Stoeckert, Christian, Weng, Chunhua, Diehl, Alexander D, Mungall, Christopher J, Haendel, Melissa, Robinson, Peter N, Himmelfarb, Jonathan, Iyengar, Ravi, Kretzler, Matthias, Mooney, Sean, and He, Yongqun

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Kidney Disease, Networking and Information Technology R&D (NITRD), Generic health relevance, Renal and urogenital, Good Health and Well Being, Atlases as Topic, Big Data, Biological Ontologies, Humans, Kidney Diseases, Phenotype, Precision Medicine, Kidney Precision Medicine Project, Urology & Nephrology, Clinical sciences
Abstract

An important need exists to better understand and stratify kidney disease according to its underlying pathophysiology in order to develop more precise and effective therapeutic agents. National collaborative efforts such as the Kidney Precision Medicine Project are working towards this goal through the collection and integration of large, disparate clinical, biological and imaging data from patients with kidney disease. Ontologies are powerful tools that facilitate these efforts by enabling researchers to organize and make sense of different data elements and the relationships between them. Ontologies are critical to support the types of big data analysis necessary for kidney precision medicine, where heterogeneous clinical, imaging and biopsy data from diverse sources must be combined to define a patient's phenotype. The development of two new ontologies - the Kidney Tissue Atlas Ontology and the Ontology of Precision Medicine and Investigation - will support the creation of the Kidney Tissue Atlas, which aims to provide a comprehensive molecular, cellular and anatomical map of the kidney. These ontologies will improve the annotation of kidney-relevant data, and eventually lead to new definitions of kidney disease in support of precision medicine.

Published
2020

5. A comprehensive update on CIDO: the community-based coronavirus infectious disease ontology

Author

He, Yongqun, Yu, Hong, Huffman, Anthony, Lin, Asiyah Yu, Natale, Darren A., Beverley, John, Zheng, Ling, Perl, Yehoshua, Wang, Zhigang, Liu, Yingtong, Ong, Edison, Wang, Yang, Huang, Philip, Tran, Long, Du, Jinyang, Shah, Zalan, Shah, Easheta, Desai, Roshan, Huang, Hsin-hui, Tian, Yujia, Merrell, Eric, Duncan, William D., Arabandi, Sivaram, Schriml, Lynn M., Zheng, Jie, Masci, Anna Maria, Wang, Liwei, Liu, Hongfang, Smaili, Fatima Zohra, Hoehndorf, Robert, Pendlington, Zoë May, Roncaglia, Paola, Ye, Xianwei, Xie, Jiangan, Tang, Yi-Wei, Yang, Xiaolin, Peng, Suyuan, Zhang, Luxia, Chen, Luonan, Hur, Junguk, Omenn, Gilbert S., Athey, Brian, and Smith, Barry

Published
2022
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6. CanVaxKB: a web-based cancer vaccine knowledgebase

Author

Asfaw, Eliyas, primary, Lin, Asiyah Yu, additional, Huffman, Anthony, additional, Li, Siqi, additional, George, Madison, additional, Darancou, Chloe, additional, Kalter, Madison, additional, Wehbi, Nader, additional, Bartels, Davis, additional, Fleck, Elyse, additional, Tran, Nancy, additional, Faghihnia, Daniel, additional, Berke, Kimberly, additional, Sutariya, Ronak, additional, Reyal, Farah, additional, Tammam, Youssef, additional, Zhao, Bin, additional, Ong, Edison, additional, Xiang, Zuoshuang, additional, He, Virginia, additional, Song, Justin, additional, Seleznev, Andrey I, additional, Guo, Jinjing, additional, Pan, Yuanyi, additional, Zheng, Jie, additional, and He, Yongqun, additional

Published
2024
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9. Ontobee: A linked ontology data server to support ontology term dereferencing, linkage, query and integration

Author

Ong, Edison, Xiang, Zuoshuang, Zhao, Bin, Liu, Yue, Lin, Yu, Zheng, Jie, Mungall, Chris, Courtot, Mélanie, Ruttenberg, Alan, and He, Yongqun

Subjects
Networking and Information Technology R&D (NITRD), Biological Ontologies, Databases, Factual, Software, Web Browser, Environmental Sciences, Biological Sciences, Information and Computing Sciences, Developmental Biology
Abstract

Linked Data (LD) aims to achieve interconnected data by representing entities using Unified Resource Identifiers (URIs), and sharing information using Resource Description Frameworks (RDFs) and HTTP. Ontologies, which logically represent entities and relations in specific domains, are the basis of LD. Ontobee (http://www.ontobee.org/) is a linked ontology data server that stores ontology information using RDF triple store technology and supports query, visualization and linkage of ontology terms. Ontobee is also the default linked data server for publishing and browsing biomedical ontologies in the Open Biological Ontology (OBO) Foundry (http://obofoundry.org) library. Ontobee currently hosts more than 180 ontologies (including 131 OBO Foundry Library ontologies) with over four million terms. Ontobee provides a user-friendly web interface for querying and visualizing the details and hierarchy of a specific ontology term. Using the eXtensible Stylesheet Language Transformation (XSLT) technology, Ontobee is able to dereference a single ontology term URI, and then output RDF/eXtensible Markup Language (XML) for computer processing or display the HTML information on a web browser for human users. Statistics and detailed information are generated and displayed for each ontology listed in Ontobee. In addition, a SPARQL web interface is provided for custom advanced SPARQL queries of one or multiple ontologies.

Published
2017

10. A scalable method for molecular network reconstruction identifies properties of targets and mutations in acute myeloid leukemia

Author

Ong, Edison, Szedlak, Anthony, Kang, Yunyi, Smith, Peyton, Smith, Nicholas, McBride, Madison, Finlay, Darren, Vuori, Kristiina, Mason, James, Ball, Edward D., Piermarocchi, Carlo, and Paternostro, Giovanni

Subjects
Quantitative Biology - Molecular Networks, Quantitative Biology - Quantitative Methods
Abstract

A key aim of systems biology is the reconstruction of molecular networks, however we do not yet have networks that integrate information from all datasets available for a particular clinical condition. This is in part due to the limited scalability, in terms of required computational time and power, of existing algorithms. Network reconstruction methods should also be scalable in the sense of allowing scientists from different backgrounds to efficiently integrate additional data. We present a network model of acute myeloid leukemia (AML). In the current version (AML 2.1) we have used gene expression data (both microarray and RNA-seq) from five different studies comprising a total of 771 AML samples and a protein-protein interactions dataset. Our scalable network reconstruction method is in part based on the well-known property of gene expression correlation among interacting molecules. The difficulty of distinguishing between direct and indirect interactions is addressed optimizing the coefficient of variation of gene expression, using a validated gold standard dataset of direct interactions. Computational time is much reduced compared to other network reconstruction methods. A key feature is the study of the reproducibility of interactions found in independent clinical datasets. An analysis of the most significant clusters, and of the network properties (intraset efficiency, degree, betweenness centrality and PageRank) of common AML mutations demonstrated the biological significance of the network. A statistical analysis of the response of blast cells from eleven AML patients to a library of kinase inhibitors provided an experimental validation of the network. A combination of network and experimental data identified CDK1, CDK2, CDK4 and CDK6 and other kinases as potential therapeutic targets in AML.

Published
2014
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11. A Scalable Method for Molecular Network Reconstruction Identifies Properties of Targets and Mutations in Acute Myeloid Leukemia

Author

Ong, Edison, Szedlak, Anthony, Kang, Yunyi, Smith, Peyton, Smith, Nicholas, McBride, Madison, Finlay, Darren, Vuori, Kristiina, Mason, James, Ball, Edward D, Piermarocchi, Carlo, and Paternostro, Giovanni

Subjects
Biochemistry and Cell Biology, Bioinformatics and Computational Biology, Biological Sciences, Bioengineering, Genetics, Pediatric Cancer, Pediatric Research Initiative, Pediatric, Networking and Information Technology R&D (NITRD), Hematology, Rare Diseases, Cancer, Childhood Leukemia, Biotechnology, Antineoplastic Agents, Gene Expression Regulation, Leukemic, Gene Ontology, Gene Regulatory Networks, Humans, Leukemia, Myeloid, Acute, Molecular Targeted Therapy, Mutation, Protein Interaction Maps, Protein Kinase Inhibitors, Reproducibility of Results, Transcriptome, acute myeloid leukemia, gene networks, Mathematical Sciences, Information and Computing Sciences, Bioinformatics, Biological sciences, Information and computing sciences, Mathematical sciences
Abstract

A key aim of systems biology is the reconstruction of molecular networks. We do not yet, however, have networks that integrate information from all datasets available for a particular clinical condition. This is in part due to the limited scalability, in terms of required computational time and power, of existing algorithms. Network reconstruction methods should also be scalable in the sense of allowing scientists from different backgrounds to efficiently integrate additional data. We present a network model of acute myeloid leukemia (AML). In the current version (AML 2.1), we have used gene expression data (both microarray and RNA-seq) from 5 different studies comprising a total of 771 AML samples and a protein-protein interactions dataset. Our scalable network reconstruction method is in part based on the well-known property of gene expression correlation among interacting molecules. The difficulty of distinguishing between direct and indirect interactions is addressed by optimizing the coefficient of variation of gene expression, using a validated gold-standard dataset of direct interactions. Computational time is much reduced compared to other network reconstruction methods. A key feature is the study of the reproducibility of interactions found in independent clinical datasets. An analysis of the most significant clusters, and of the network properties (intraset efficiency, degree, betweenness centrality, and PageRank) of common AML mutations demonstrated the biological significance of the network. A statistical analysis of the response of blast cells from 11 AML patients to a library of kinase inhibitors provided an experimental validation of the network. A combination of network and experimental data identified CDK1, CDK2, CDK4, and CDK6 and other kinases as potential therapeutic targets in AML.

Published
2015

12. Prediction of kinase inhibitor response using activity profiling, in-vitro screening, and elastic net regression

Author

Tran, Trish, Ong, Edison, Hodges, Andrew P., Paternostro, Giovanni, and Piermarocchi, Carlo

Subjects
Quantitative Biology - Quantitative Methods, Quantitative Biology - Molecular Networks
Abstract

Many kinase inhibitors have been approved as cancer therapies. Recently, libraries of kinase inhibitors have been extensively profiled, thus providing a map of the strength of action of each compound on a large number of its targets. These profiled libraries define drug-kinase networks that can predict the effectiveness of new untested drugs and elucidate the role played by specific kinases in different cellular systems. Predictions of drug effectiveness based on a comprehensive network model of cellular signalling are difficult, due to our partial knowledge of the complex biological processes downstream of the targeted kinases. We have developed the Kinase Inhibitors Elastic Net (KIEN) method, which integrates information contained in drug-kinase networks with in vitro screening. The method uses the in vitro cell response of single drugs and drug pair combinations as a training set to build linear and nonlinear regression models. Besides predicting the effectiveness of untested drugs, the method identifies sets of kinases that are statistically associated to drug sensitivity in a given cell line. We compare different versions of the method, which is based on a regression technique known as elastic net. Data from two-drug combinations leads to predictive models, and predictivity can be improved by applying logarithmic transformation to the data. The method is applied to the A549 lung cancer cell line. A pathway enrichment analysis of the set of kinases identified by the method shows that axon guidance, activation of Rac, and semaphorin interactions pathways are associated to a selective response to therapeutic intervention in this cell line.

Published
2013
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13. The RSVPreF3-AS01 vaccine elicits broad neutralization of contemporary and antigenically distant respiratory syncytial virus strains

Author

Sacconnay, Lionel, primary, De Smedt, Jonathan, additional, Rocha-Perugini, Vera, additional, Ong, Edison, additional, Mascolo, Romuald, additional, Atas, Anne, additional, Vanden Abeele, Carline, additional, de Heusch, Magali, additional, De Schrevel, Nathalie, additional, David, Marie-Pierre, additional, Bouzya, Badiaa, additional, Stobbelaar, Kim, additional, Vanloubbeeck, Yannick, additional, Delputte, Peter L., additional, Mallett, Corey P., additional, Dezutter, Nancy, additional, and Warter, Lucile, additional

Published
2023
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19. A new framework for host-pathogen interaction research

Author

Yu, Hong, primary, Li, Li, additional, Huffman, Anthony, additional, Beverley, John, additional, Hur, Junguk, additional, Merrell, Eric, additional, Huang, Hsin-hui, additional, Wang, Yang, additional, Liu, Yingtong, additional, Ong, Edison, additional, Cheng, Liang, additional, Zeng, Tao, additional, Zhang, Jingsong, additional, Li, Pengpai, additional, Liu, Zhiping, additional, Wang, Zhigang, additional, Zhang, Xiangyan, additional, Ye, Xianwei, additional, Handelman, Samuel K., additional, Sexton, Jonathan, additional, Eaton, Kathryn, additional, Higgins, Gerry, additional, Omenn, Gilbert S., additional, Athey, Brian, additional, Smith, Barry, additional, Chen, Luonan, additional, and He, Yongqun, additional

Published
2022
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21. Additional file 3 of A comprehensive update on CIDO: the community-based coronavirus infectious disease ontology

Author

He, Yongqun, Yu, Hong, Huffman, Anthony, Lin, Asiyah Yu, Natale, Darren A., Beverley, John, Zheng, Ling, Perl, Yehoshua, Wang, Zhigang, Liu, Yingtong, Ong, Edison, Wang, Yang, Huang, Philip, Tran, Long, Du, Jinyang, Shah, Zalan, Shah, Easheta, Desai, Roshan, Huang, Hsin-hui, Tian, Yujia, Merrell, Eric, Duncan, William D., Arabandi, Sivaram, Schriml, Lynn M., Zheng, Jie, Masci, Anna Maria, Wang, Liwei, Liu, Hongfang, Smaili, Fatima Zohra, Hoehndorf, Robert, Pendlington, Zoë May, Roncaglia, Paola, Ye, Xianwei, Xie, Jiangan, Tang, Yi-Wei, Yang, Xiaolin, Peng, Suyuan, Zhang, Luxia, Chen, Luonan, Hur, Junguk, Omenn, Gilbert S., Athey, Brian, and Smith, Barry

Abstract

Additional file 3: Supplemental Table 2. CIDO statistics including terms imported from major reference ontologies.

Published
2022
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22. Additional file 2 of A comprehensive update on CIDO: the community-based coronavirus infectious disease ontology

Author

He, Yongqun, Yu, Hong, Huffman, Anthony, Lin, Asiyah Yu, Natale, Darren A., Beverley, John, Zheng, Ling, Perl, Yehoshua, Wang, Zhigang, Liu, Yingtong, Ong, Edison, Wang, Yang, Huang, Philip, Tran, Long, Du, Jinyang, Shah, Zalan, Shah, Easheta, Desai, Roshan, Huang, Hsin-hui, Tian, Yujia, Merrell, Eric, Duncan, William D., Arabandi, Sivaram, Schriml, Lynn M., Zheng, Jie, Masci, Anna Maria, Wang, Liwei, Liu, Hongfang, Smaili, Fatima Zohra, Hoehndorf, Robert, Pendlington, Zoë May, Roncaglia, Paola, Ye, Xianwei, Xie, Jiangan, Tang, Yi-Wei, Yang, Xiaolin, Peng, Suyuan, Zhang, Luxia, Chen, Luonan, Hur, Junguk, Omenn, Gilbert S., Athey, Brian, and Smith, Barry

Abstract

Additional file 2: Supplemental Table 1. Resources used for our coronavirus disease-related data collection.

Published
2022
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23. Additional file 1 of A comprehensive update on CIDO: the community-based coronavirus infectious disease ontology

Author

He, Yongqun, Yu, Hong, Huffman, Anthony, Lin, Asiyah Yu, Natale, Darren A., Beverley, John, Zheng, Ling, Perl, Yehoshua, Wang, Zhigang, Liu, Yingtong, Ong, Edison, Wang, Yang, Huang, Philip, Tran, Long, Du, Jinyang, Shah, Zalan, Shah, Easheta, Desai, Roshan, Huang, Hsin-hui, Tian, Yujia, Merrell, Eric, Duncan, William D., Arabandi, Sivaram, Schriml, Lynn M., Zheng, Jie, Masci, Anna Maria, Wang, Liwei, Liu, Hongfang, Smaili, Fatima Zohra, Hoehndorf, Robert, Pendlington, Zoë May, Roncaglia, Paola, Ye, Xianwei, Xie, Jiangan, Tang, Yi-Wei, Yang, Xiaolin, Peng, Suyuan, Zhang, Luxia, Chen, Luonan, Hur, Junguk, Omenn, Gilbert S., Athey, Brian, and Smith, Barry

Abstract

Additional file 1: Supplemental file 1. Visualization of the Evolution of CIDO.

Published
2022
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24. A new framework for hostpathogen interaction research.

Author

Hong Yu, Li Li, Huffman, Anthony, Beverley, John, Hur, Junguk, Merrell, Eric, Hsin-hui Huang, Yang Wang, Yingtong Liu, Ong, Edison, Liang Cheng, Tao Zeng, Jingsong Zhang, Pengpai Li, Zhiping Liu, Zhigang Wang, Xiangyan Zhang, Xianwei Ye, Handelman, Samuel K., and Sexton, Jonathan

Subjects
DRUG design, COVID-19, COMMUNICABLE diseases, PROTEIN-protein interactions
Abstract

COVID-19 often manifests with different outcomes in different patients, highlighting the complexity of the host-pathogen interactions involved in manifestations of the disease at the molecular and cellular levels. In this paper, we propose a set of postulates and a framework for systematically understanding complex molecular host-pathogen interaction networks. Specifically, we first propose four host-pathogen interaction (HPI) postulates as the basis for understanding molecular and cellular host-pathogen interactions and their relations to disease outcomes. These four postulates cover the evolutionary dispositions involved in HPIs, the dynamic nature of HPI outcomes, roles that HPI components may occupy leading to such outcomes, and HPI checkpoints that are critical for specific disease outcomes. Based on these postulates, an HPI Postulate and Ontology (HPIPO) framework is proposed to apply interoperable ontologies to systematically model and represent various granular details and knowledge within the scope of the HPI postulates, in a way that will support AI-ready data standardization, sharing, integration, and analysis. As a demonstration, the HPI postulates and the HPIPO framework were applied to study COVID-19 with the Coronavirus Infectious Disease Ontology (CIDO), leading to a novel approach to rational design of drug/vaccine cocktails aimed at interrupting processes occurring at critical host-coronavirus interaction checkpoints. Furthermore, the host-coronavirus protein-protein interactions (PPIs) relevant to COVID-19 were predicted and evaluated based on prior knowledge of curated PPIs and domain-domain interactions, and how such studies can be further explored with the HPI postulates and the HPIPO framework is discussed. [ABSTRACT FROM AUTHOR]

Published
2022
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27. VaximmutorDB: A Web-Based Vaccine Immune Factor Database and Its Application for Understanding Vaccine-Induced Immune Mechanisms

Author

Berke, Kimberly, primary, Sun, Peter, additional, Ong, Edison, additional, Sanati, Nasim, additional, Huffman, Anthony, additional, Brunson, Timothy, additional, Loney, Fred, additional, Ostrow, Joseph, additional, Racz, Rebecca, additional, Zhao, Bin, additional, Xiang, Zuoshuang, additional, Masci, Anna Maria, additional, Zheng, Jie, additional, Wu, Guanming, additional, and He, Yongqun, additional

Published
2021
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35. Towards precision informatics of pharmacovigilance: OAE-CTCAE mapping and OAE-based representation and analysis of adverse events in patients treated with cancer drugs

Author

Wong, Mei U, Racz, Rebecca, Ong, Edison, and He, Yongqun

Subjects
Pharmacovigilance, Biological Ontologies, Drug-Related Side Effects and Adverse Reactions, Neoplasms, Humans, Antineoplastic Agents, Articles, Severity of Illness Index, Medical Informatics, Semantics
Abstract

A critical issue in the usage of cancer drugs is its association with various adverse events (AEs) in some, but not all, patients. The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) is a controlled terminology for AE classification and analysis in cancer clinical trials. The Ontology of Adverse Events (OAE) is a community-based ontology in the domain of AEs. In this study, OAE was first updated by including AE severity grading and OAE-CTCAE mapping. An OAE subset containing CTCAE-related terms and their associated OAE terms was generated to facilitate term usage. A use case study based on a published cancer drug clinical trial demonstrates that OAE provides better hierarchical representation, includes semantic relations, and supports automated reasoning. Demonstrated with a single patient analysis, the OAE framework supports precision informatics for representing AEs and related genetic and clinical conditions in individual patients treated with cancer drugs.

Published
2018

36. Victors: a web-based knowledge base of virulence factors in human and animal pathogens

Author

Sayers, Samantha, primary, Li, Li, additional, Ong, Edison, additional, Deng, Shunzhou, additional, Fu, Guanghua, additional, Lin, Yu, additional, Yang, Brian, additional, Zhang, Shelley, additional, Fa, Zhenzong, additional, Zhao, Bin, additional, Xiang, Zuoshuang, additional, Li, Yongqing, additional, Zhao, Xing-Ming, additional, Olszewski, Michal A, additional, Chen, Luonan, additional, and He, Yongqun, additional

Published
2018
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42. Integrative representation and analysis of the LINCS cell lines using the Cell Line Ontology

Author

Ong, Edison, Jiangan Xie, Zhaohui Ni, Lin, Yu, Stathias, Vasileios, Chung, Caty, Schürer, Stephan, and Yongqun He

Abstract

Cell lines are crucial to study molecular signatures and pathways, and are widely used in the NIH Common Fund LINCS project. The Cell Line Ontology (CLO) is a community-based ontology representing and classifying cell lines from different resources. To better serve the LINCS research community, from the LINCS Data Portal and ChEMBL we identified 1,097 LINCS cell lines among which 717 cell lines were associated with 121 cancer types. 352 cell line terms did not exist in CLO. To harmonize LINCS cell line representation and CLO, CLO design patterns were slightly updated to add new information of the LINCS cell lines including different database cross-reference IDs. A new shortcut relation was generated to directly link a cell line to the disease of the patient from whom the cell line was originated. After new LINCS cell lines and related information were added to CLO, a CLO subset/view (LINCS-CLOview) of LINCS cell lines was generated and analyzed to identify scientific insights into these LINCS cell lines. Furthermore, we used the LINCS-CLOview to link and analyze various data generated from different LINCS cell lines. This study provides a first time use case on how CLO can be updated and applied to support cell line research from a specific research community or project initiative.

Published
2016
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