Article
Biochemistry & Molecular Biology
Chi-Cheng Huang, Chih-Yi Liu, Chi-Jung Huang, Yao-Chun Hsu, Heng-Hui Lien, Jia-Uei Wong, Feng-Chuan Tai, Wen-Hui Ku, Chi-Feng Hung, Jaw-Town Lin, Ching-Shui Huang, Han-Sun Chiang
Summary: Pancreatic adenocarcinoma (PAC) is the 8th leading cause of cancer-related deaths in Taiwan, and its incidence is increasing. Targeted next-generation sequencing can identify somatic mutations in PAC patients, providing insights into the molecular changes and potential therapeutic options.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemical Research Methods
Weili Miao, David Bade, Yinsheng Wang
Summary: The study utilized SILAC and PRM methods to investigate the differential expression of kinases in breast cancer cells, revealing that the differentially expressed kinase TAF9 enhances radioresistance in breast cancer cells and plays a role in upregulating genes associated with radioresistance.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Multidisciplinary Sciences
David R. Blair, Thomas J. Hoffmann, Joseph T. Shieh
Summary: This study investigates the relationship between the severity of rare genetic diseases and common genetic variations using biobank-scale clinical and genetic data. The study develops a model-based approach to infer quantitative traits capturing disease-related phenotypic variability and identifies common genetic variations that predict the diagnosis and outcomes of Mendelian diseases.
NATURE COMMUNICATIONS
(2022)
Article
Agronomy
Kai Sun, Dandan Li, Aoyun Xia, Hua Zhao, Qin Wen, Sisi Jia, Jiafeng Wang, Guili Yang, Danhua Zhou, Cuihong Huang, Hui Wang, Zhiqiang Chen, Tao Guo
Summary: In this study, extensive variation in granulotype in rice was observed through targeted sequencing and whole genome sequencing. Key mutants and new allelic variants associated with grain type were identified, providing valuable information for molecular breeding and genotype mutation analysis. The proposed method combining targeted sequencing of mixed samples and whole genome sequencing proved to be cost-effective, efficient, and flexible for trait and gene detection.
Article
Pathology
Cedric Chuan Young Ng, Nur Diyana Md Nasir, Benjamin Nathanael Loke, Timothy Kwang Yong Tay, Aye Aye Thike, Vikneswari Rajasegaran, Wei Liu, Jing Yi Lee, Peiyong Guan, Abner Herbert Lim, Kenneth Tou En Chang, Mihir Ananta Gudi, Preetha Madhukumar, Benita Kiat Tee Tan, Veronique Kiak Mien Tan, Chow Yin Wong, Wei Sean Yong, Gay Hui Ho, Kong Wee Ong, George Wai Cheong Yip, Boon Huat Bay, Patrick Tan, Bin Tean Teh, Puay Hoon Tan
Summary: This study analyzed genetic mutations in breast fibroepithelial lesions, finding that benign phyllodes tumors have more mutations and higher rates of cancer driver gene alterations compared to fibroadenomas. Cases with MED12 mutations were also more likely to have other key mutations. TERT promoter alterations were most effective in distinguishing between different types of lesions in the breast.
Article
Biochemistry & Molecular Biology
Yizhou Yin, Matthew G. Romei, Kannan Sankar, Lipika R. Pal, Kam Hon Hoi, Yanli Yang, Brandon Leonard, Gladys De Leon Boenig, Nikit Kumar, Marissa Matsumoto, Jian Payandeh, Seth F. Harris, John Moult, Greg A. Lazar
Summary: This study analyzed and characterized the structural interactions of the antibody fragment antigen-binding (Fab) regions, leading to the discovery of previously unnoticed interfaces between antibodies. Experimental validation revealed the potential of these interfaces and provided new opportunities for their drug optimization.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Urology & Nephrology
Anthony J. Bleyer, Maggie Westemeyer, Jing Xie, Michelle S. Bloom, Katya Brossart, Jason J. Eckel, Frederick Jones, Miklos Z. Molnar, Wayne Kotzker, Prince Anand, Stanislav Kmoch, Yuan Xue, Samuel Strom, Sumit Punj, Zachary P. Demko, Hossein Tabriziani, Paul R. Billings, Trudy McKanna
Summary: The use of broad panel genetic testing by clinical nephrologists had a high success rate, similar to results obtained by academic centers specializing in genetics. Positive genetic findings were identified in 21.1% of cases, with the most common gene variants being PKD1, COL4A5, PKD2, COL4A4, COL4A3, and TTR.
AMERICAN JOURNAL OF NEPHROLOGY
(2022)
Article
Oncology
Hee Young Na, Jeong Hwan Park, Sun Ah Shin, Sejoon Lee, Heonyi Lee, Heejoon Chae, HoKyung Choung, Namju Kim, Jin-Haeng Chung, Ji Eun Kim
Summary: This study investigated genetic alterations in ocular and extraocular sebaceous carcinoma in Korean patients, revealing distinct genetic differences between the two types of tumors and identifying important prognostic molecular markers. Mutations in potentially actionable genes were noted, suggesting consideration of clinical trials in intractable cases.
Article
Biochemical Research Methods
Yan Zheng, Xuequn Shang
Summary: Researchers propose a new deep learning-based method, SVcnn, for detecting structural variations (SVs) using long-read sequencing data. The method outperforms other SV callers, improving F1-score by 2-8% when the read depth is greater than 5x. It also shows better performance in detecting multi-allelic SVs.
BMC BIOINFORMATICS
(2023)
Article
Multidisciplinary Sciences
Anke Faehnrich, Isabel Stephan, Misa Hirose, Franziska Haarich, Mosab Ali Awadelkareem, Saleh Ibrahim, Hauke Busch, Inken Wohlers
Summary: This study created the most comprehensive quality-controlled North and East African mitochondrial dataset to date and used it to characterize mitochondrial genetic variation in this region. The study identified previously unexplored common variants in mitochondrial genomes of North and East Africa, leading to novel phylogenetic relationships between haplogroups present in these regions.
JOURNAL OF ADVANCED RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Natalia Kunowska, Ulrich Stelzl
Summary: Genetic differences mainly affect the abundance and stoichiometry of protein complexes, while large-scale binary interaction analyses show that loss of interaction is widespread and caused by disease-associated mutations. Through protein-protein interactions, genetic variation ultimately affects the functional consequences of the cellular proteome.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2022)
Article
Genetics & Heredity
Xiangyin Liu, Han Zhang, Xinyue Zhang, Hongguo Zhang, Yuting Jiang, Ruizhi Liu, Jia Fei, Ying Wang, Yang Yu
Summary: The NGS method was validated as an alternative to traditional STS-PCR method for detecting Y chromosome microdeletions in infertile men. It not only detects CNV like partial deletion or duplication, but also provides detailed information on the abnormal range and size of variations.
JOURNAL OF ASSISTED REPRODUCTION AND GENETICS
(2021)
Article
Biochemical Research Methods
Yadong Liu, Tao Jiang, Junhao Su, Bo Liu, Tianyi Zang, Yadong Wang
Summary: The SKSV toolkit is proposed for detecting structural variations, which shows a significantly faster speed and higher F1 scores compared to state-of-the-art SV calling approaches.
Article
Biochemistry & Molecular Biology
Bailing Zu, Xiaoqing Zhang, Yunlan Xu, Ying Xiang, Zhigang Wang, Haiqing Cai, Bo Wang, Guoling You, Qihua Fu
Summary: By conducting targeted sequencing analysis on 181 patients, a high frequency of deleterious variants in patients with polydactyly was identified, providing an efficient method for genetic diagnosis with a positive molecular diagnostic rate of 7.7%.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Biotechnology & Applied Microbiology
Nicolas Dierckxsens, Tong Li, Joris R. Vermeesch, Zhi Xie
Summary: Accurate simulations of structural variation distributions and sequencing data are essential for new tool development and benchmarking. The Sim-it tool is developed to simulate both structural variation and long-read data, revealing strengths and weaknesses of current available tools. Using these findings, the combiSV method is introduced to combine results from structural variation callers, resulting in a superior call set with increased recall and precision.
Article
Multidisciplinary Sciences
Jonathan Poh, Kao Chin Ngeow, Michelle Pek, Kian-Hin Tan, Jing Shan Lim, Hao Chen, Choon Kiat Ong, Jing Quan Lim, Soon Thye Lim, Chwee Ming Lim, Boon Cher Goh, Yukti Choudhury
Summary: Next-generation sequencing of circulating tumor DNA offers a promising approach to cancer diagnostics, providing minimally invasive serial testing and broad genomic coverage through a simple blood draw, maximizing therapeutic benefit for patients.
Article
Oncology
Le Ying, Phoebe Liu, Zhoujie Ding, Georgie Wray-McCann, Jack Emery, Nina Colon, Lena H. M. Le, Le Son Tran, Ping Xu, Liang Yu, Dana J. Philpott, Yugang Tu, Daryl M. Z. Cheah, Chee L. Cheng, Soon T. Lim, Choon K. Ong, Richard L. Ferrero
Summary: This study established a new mouse model to study gastric MALT lymphoma and found that mice with a myeloid-specific deletion of Nlrc5 develop precursor B-cell lesions to MALT lymphoma after Helicobacter infection in a shorter time. The lesions in these mice have similar histopathological features to the human disease and are accompanied by an immunosuppressive tissue microenvironment. The study also demonstrated that anti-CD40L antibody can prevent gastric B-cell lesions in mice and reduce the number of immune cells in the stomach.
JOURNAL OF PATHOLOGY
(2023)
Correction
Multidisciplinary Sciences
Lina Sieverling, Chen Hong, Sandra D. Koser, Philip Ginsbach, Kortine Kleinheinz, Barbara Hutter, Delia M. Braun, Isidro Cortes-Ciriano, Ruibin Xi, Rolf Kabbe, Peter J. Park, Roland Eils, Matthias Schlesner, Benedikt Brors, Karsten Rippe, David T. W. Jones, Lars Feuerbach
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Jinghong Chen, Zhixiang Zuo, Yan Gao, Xiaosai Yao, Peiyong Guan, Yali Wang, Zhimei Li, Zhilong Liu, Jing Han Hong, Peng Deng, Jason Yongsheng Chan, Daryl Ming Zhe Cheah, Jingquan Lim, Kelila Xin Ye Chai, Burton Kuan Hui Chia, Jane Wan Lu Pang, Joanna Koh, Dachuan Huang, Haixia He, Yichen Sun, Lizhen Liu, Shini Liu, Yuhua Huang, Xiaoxiao Wang, Hua You, Sahil Ajit Saraf, Nicholas Francis Grigoropoulos, Xiaoqiu Li, Jinxin Bei, Tiebang Kang, Soon Thye Lim, Bin Tean Teh, Huiqiang Huang, Choon Kiat Ong, Jing Tan
Summary: This study suggests that combination therapy with chidamide and JAK-STAT inhibitors can be a novel targeted therapy in the standard of care for NKTL (Natural killer/T-cell lymphoma).
CLINICAL EPIGENETICS
(2023)
Review
Immunology
Daniel Ren Yi Yap, Jing Quan Lim, Dachuan Huang, Choon Kiat Ong, Jason Yongsheng Chan
Summary: Peripheral T-cell lymphoma (PTCL) and natural killer/T-cell lymphoma (NKTCL) are rare subtypes of non-Hodgkin's lymphoma with poor treatment outcomes. Current treatment strategies involve combination chemoimmunotherapy, radiation, and/or stem cell transplant. However, there is a lack of validated biomarkers for personalized therapy, leading to high failure rates and missed treatment opportunities. Recent research advancements have improved our understanding of these diseases, but clinical translation is still hindered. This review summarizes the progress and challenges in predictive biomarker landscape and implications for novel therapeutics development in PTCL and NKTCL.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jianfeng Chen, Jing Han Hong, Yulin Huang, Shini Liu, Jiaxin Yin, Peng Deng, Yichen Sun, Zhaoliang Yu, Xian Zeng, Rong Xiao, Jason Yongsheng Chan, Peiyong Guan, Yali Wang, Peili Wang, Lizhen Liu, Shijun Wen, Qiang Yu, Choon Kiat Ong, Bin-Tean Teh, Ying Xiong, Jing Tan
Summary: This study reveals that EZH2 plays an oncogenic role in ovarian cancer through noncatalytic activity. Inhibition of EZH2 degradation, rather than its catalytic activity, can effectively block ovarian cancer growth and tumor formation. Furthermore, EZH2 has extensive occupancy at promoters independent of PRC2 and can upregulate IDH2 to promote metabolic rewiring and contribute to ovarian cancer growth.
Article
Biochemistry & Molecular Biology
Jianbiao Zhou, Sabrina Hui-Min Toh, Tze King Tan, Kalpnaa Balan, Jing Quan Lim, Tuan Zea Tan, Sinan Xiong, Yunlu Jia, Siok-Bian Ng, Yanfen Peng, Anand D. Jeyasekharan, Shuangyi Fan, Soon Thye Lim, Chin-Ann Johnny Ong, Choon Kiat Ong, Takaomi Sanda, Wee-Joo Chng
Summary: This study identified several super-enhancers (SEs) associated with key transcription factor (TF) genes in extranodal natural killer/T-cell lymphoma (NKTL), including a novel SE named TOX2. Overexpression of TOX2 was found to be associated with worse survival in NKTL patients. Modulating the expression of TOX2 affected the proliferation, survival, and colony formation ability of NKTL cells. Furthermore, a downstream effector of TOX2-mediated oncogenesis, PRL-3, was identified and validated.
Article
Oncology
Michal Marek Hoppe, Patrick Jaynes, Shuangyi Fan, Yanfen Peng, Shruti Sridhar, Phuong Mai Hoang, Clementine Xin Liu, Sanjay De Mel, Limei Poon, Esther Hian Li Chan, Joanne Lee, Choon Kiat Ong, Tiffany Tang, Soon Thye Lim, Chandramouli Nagarajan, Nicholas F. Grigoropoulos, Soo-Yong Tan, Susan Swee-Shan Hue, Sheng-Tsung Change, Shih-Sung Chuange, Shaoying Li, Joseph D. Khoury, Hyungwon Choi, Carl Harris III, Alessia Bottos, Laura J. Gay, Hendrik F. P. Runge, Ilias Moutsopoulos, Irina Mohorianu, Daniel J. Hodson, Pedro Farinha, Anja Mottok, David W. Scott, Jason J. Pitt, Jinmiao Chen, Gayatri Kumar, Kasthuri Kannan, Wee Joo Chug, Yen Lin Chee, Siok-Bia Ng, Claudio Tripodoe, Anand D. Jeyasekharan
Summary: This study demonstrates that combinations of oncogenes in cellular subpopulations within a cancer can influence clinical outcomes. The percentage of cells with a unique combination of MYC, BCL2, and BCL6 predicts survival in diffuse large B-cell lymphoma (DLBCL), and can be derived mathematically from quantitative measurements of the individual oncogenes. Comparative analysis of DLBCL samples and transformed B cells identifies potential regulators of the unfavorable biology associated with this combination. These findings have implications for understanding cancer evolution and therapy resistance.
Article
Biology
Jui Wan Loh, Jing Yi Lee, Abner Herbert Lim, Peiyong Guan, Boon Yee Lim, Bavani Kannan, Elizabeth Chun Yong Lee, Ning Xin Gu, Tun Kiat Ko, Cedric Chuan-Young Ng, Jeffrey Chun Tatt Lim, Joe Yeong, Jing Quan Lim, Choon Kiat Ong, Bin Tean Teh, Jason Yongsheng Chan
Summary: A genomic and transcriptomic analysis of angiosarcomas, including samples from the head and neck region, revealed recurrent mutations in CSMD3, LRP1B, MUC16, POT1, and TP53 genes. The study also found that UV-positive angiosarcomas have a higher tumor mutation burden than UV-negative cases. Spatial transcriptomics identified the tumor immune landscape of angiosarcomas, providing insights for the implementation of treatment strategies.
COMMUNICATIONS BIOLOGY
(2023)
Article
Cell Biology
Xiao-Peng Tian, Yu-Chen Zhang, Ning-Jing Lin, Liang Wang, Zhi-Hua Li, Han-Guo Guo, Shu-Yun Ma, Ming-Jie An, Jing Yang, Yu-Heng Hong, Xian-Huo Wang, Hui Zhou, Ya-Jun Li, Hui-Lan Rao, Mei Li, Shao-Xuan Hu, Tong-Yu Lin, Zhi-Ming Li, He Huang, Yang Liang, Zhong-Jun Xia, Yue Lv, Yu-Ying Liu, Zhao-Hui Duan, Qing-Yu Chen, Jin-Ni Wang, Jun Cai, Ying Xie, Choon-Kiat Ong, Fang Liu, Yan-yan Liu, Zheng Yan, Liang Huang, Rong Tao, Wen-Yu Li, Hui-Qiang Huang, Qing-Qing Cai
Summary: By analyzing the methylation profiles of ENKTL plasma samples, we identified ENKTL-specific ctDNA methylation markers and established a diagnostic and prognosis prediction model. The model is based on ctDNA methylation markers with high specificity and sensitivity, closely related to tumor staging and therapeutic response. Furthermore, we developed a prognostic prediction model with excellent performance, surpassing the Ann Arbor staging and PINK risk system.
CELL REPORTS MEDICINE
(2023)
Article
Medicine, Research & Experimental
Yali Wang, Wenbo Zhou, Jianfeng Chen, Jinghong Chen, Peng Deng, Huang Chen, Yichen Sun, Zhaoliang Yu, Diwen Pang, Lizhen Liu, Peili Wang, Jing Han Hong, Bin Tean Teh, Huiqiang Huang, Wenyu Li, Zhengfang Yi, Soon Thye Lim, Yihua Chen, Choon Kiat Ong, Mingyao Liu, Jing Tan
Summary: A new and potent STAT3 inhibitor, WB737, has been developed as a potential therapeutic option for NKTL. It selectively inhibits NKTL with STAT3-activating mutations and suppresses both canonical and noncanonical STAT3 signaling. WB737 shows significant antitumor effects with minimal toxicity, providing a promising strategy for treating NKTL patients.
Article
Oncology
Esther Wei Yin Chang, Valerie Shiwen Yang, Shin Yeu Ong, Hilda Xueqi Kang, Boon Yee Lim, Sanjay de Mel, Esther Ka Yan Ng, Michelle Limei Poon, Ya Hwee Tan, Jianbang Chiang, Eileen Poon, Nagavalli Somasundaram, Mohamad Farid, Tiffany Tang, Miriam Tao, Lay Poh Khoo, Chee Leong Cheng, Dachuan Huang, Choon Kiat Ong, Soon Thye Lim, Jason Yongsheng Chan
Summary: In our multicenter study in Asia, we investigated the clinical factors that affect the outcomes of AITL patients and identified a new prognostic index relevant to Asian patients. In our cohort of 174 patients, the median PFS and OS were 1.8 years and 5.6 years, respectively. Age >60, bone marrow involvement, total white cell count >12 x 10(9)/L, and elevated serum lactate dehydrogenase were associated with poorer PFS and OS in multivariate analyses. A prognostic index (AITL-PI) was developed to categorize patients into low, moderate, and high-risk subgroups, with 5-year OS rates of 84.0%, 44.0%, and 28.0% respectively (p < 0.0001). POD24 was found to be a strong prognostic factor (5-year OS 24% vs 89%, p < 0.0001). Exploratory gene expression studies revealed distinct immune cell profiles and cell signaling signatures among the different risk groups.
LEUKEMIA & LYMPHOMA
(2023)
Review
Oncology
Jason Yongsheng Chan, Nagavalli Somasundaram, Nicholas Grigoropoulos, Francesca Lim, Michelle Limei Poon, Anand Jeyasekharan, Kheng Wei Yeoh, Daryl Tan, Georg Lenz, Choon Kiat Ong, Soon Thye Lim
Summary: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, consisting of diverse disease entities with unique molecular and clinico-pathological features. Understanding of the molecular landscape of DLBCL has improved, revealing distinct genomic subtypes with implications for targeted therapy. Recent approvals of new treatment modalities in both frontline and relapsed settings have addressed previous clinical trial challenges. However, issues such as drug accessibility, reimbursement policies, treatment sequencing, and preferences present challenges in real-world oncology practice. This review discusses recent advances in DLBCL therapeutics and their implications on healthcare practices in Singapore.
Article
Hematology
Grace Fangmin Tan, Siting Goh, Esther Wei Yin Chang, Ya Hwee Tan, Jianbang Chiang, Valerie Shiwen Yang, Eileen Yi Ling Poon, Nagavalli Somasundaram, Mohamad Farid Bin Harunal Rashid, Miriam Tao, Soon Thye Lim, Choon Kiat Ong, Jason Yongsheng Chan
Summary: Our study examines the prognostic value of immunologic changes in Hodgkin's lymphoma by investigating post-treatment lymphocyte count (pALC), neutrophil count (pANC), and the neutrophil-lymphocyte ratio (pNLR). We analyzed patients treated for classical Hodgkin's lymphoma and determined the optimal cutoff values for high pANC, low pALC, and high pNLR in predicting progression-free survival.
HEMATOLOGY REPORTS
(2023)
Article
Genetics & Heredity
Mo Liu, Yang Wu, Nanhai Jiang, Arnoud Boot, Steven G. Rozen
Summary: Mutational signatures are characteristic patterns of mutations discovered through analyzing large sets of samples. Most programs use non-negative matrix factorization (NMF), but the hierarchical Dirichlet process (HDP) mixture models approach is less explored. This study introduces mSigHdp, an improved approach using HDP mixture models to discover mutational signatures, which outperforms NMF-based approaches in terms of positive predictive value and true positive rate in benchmark tests.
NAR GENOMICS AND BIOINFORMATICS
(2023)