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Machine learning approaches to identify systemic lupus erythematosus in anti-nuclear antibody-positive patients using genomic data and electronic health records

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BioData Mining 2024年第1期17卷 1页

作者： Chung, Chih-Wei Chou, Seng-Cho Hsiao, Tzu-Hung Zhang, Grace Joyce Chung, Yu-Fang Chen, Yi-Ming Department of Information Management National Taiwan University Taipei Taiwan Department of Medical Research Taichung Veterans General Hospital Taichung Taiwan Department of Public Health Fu Jen Catholic University New Taipei Taiwan Institute of Genomics and Bioinformatics National Chung Hsing University Taichung Taiwan Department of Cellular and Physiological Sciences The University of British Columbia Vancouver BC Canada Department of Electrical Engineering Tunghai University Taichung Taiwan Division of Allergy Immunology and Rheumatology Department of Internal Medicine Taichung Veterans General Hospital 1650 Section 4 Boulevard Xitun Dist. Taichung 407 Taiwan Department of Post-Baccalaureate Medicine College of Medicine National Chung Hsing University Taichung Taiwan School of Medicine College of Medicine National Yang Ming Chiao Tung University Taipei Taiwan Rong Hsing Research Center for Translational Medicine & Ph.D. Program in Translational Medicine National Chung Hsing University Taichung Taiwan Precision Medicine Research Center College of Medicine National Chung Hsing University Taichung Taiwan

Background: Although the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus (SLE) has required at least a positive anti-nuclear antibody (ANA) titer (≥ 1:80), it remains challenging for clinicians to identify patients with SLE. This study aimed to develop a machine learning (ML) approach to assist in the detection of SLE patients using genomic data and electronic health records. Methods: Participants with a positive ANA (≥ 1:80) were enrolled from the Taiwan Precision medicine Initiative cohort. The Taiwan Biobank version 2 array was used to detect single nucleotide polymorphism (SNP) data. Six ML models, Logistic Regression, Random Forest (RF), Support Vector Machine, Light Gradient Boosting Machine, Gradient Tree Boosting, and Extreme Gradient Boosting (XGB), were used to identify SLE patients. The importance of the clinical and genetic features was determined by Shapley Additive Explanation (SHAP) values. A logistic regression model was applied to identify genetic variations associated with SLE in the subset of patients with an ANA equal to or exceeding 1:640. Results: A total of 946 SLE and 1,892 non-SLE controls were included in this analysis. Among the six ML models, RF and XGB demonstrated superior performance in the differentiation of SLE from non-SLE. The leading features in the SHAP diagram were anti-double strand DNA antibodies, ANA titers, AC4 ANA pattern, polygenic risk scores, complement levels, and SNPs. Additionally, in the subgroup with a high ANA titer (≥ 1:640), six SNPs positively associated with SLE and five SNPs negatively correlated with SLE were discovered. Conclusions: ML approaches offer the potential to assist in diagnosing SLE and uncovering novel SNPs in a group of patients with autoimmunity. © 2024, The Author(s).

关键词： Anti-nuclear antibody Machine learning Polygenic risk score Single nucleotide polymorphism Systemic lupus erythematosus

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Dissecting the epigenomic dynamics of human fetal germ cell development at single-cell resolution

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细胞研究（英文版） 2021年第4期31卷 463-477页

作者： Li Li Lin Li Qingqing Li Xixi Liu Xinyi Ma Jun Yong Shuai Gao Xinglong Wu Yuan Wei Xiaoye Wang Wei Wang Rong Li Jie Yan Xiaohui Zhu Lu Wen Jie Qiao Liying Yan Fuchou Tang Beijing Advanced Innovation Center for Genomics Department of Obstetrics and GynecologyThird HospitalSchool of Life SciencesPeking UniversityBeijing 100871China Biomedical Pioneering Innovation Center Center for Reproductive MedicineMinistry of EducationKey Laboratory of Cell Proliferation and DifferentiationBeijing 100871China Stem Cell Program Boston Children's HospitalBostonMA 02115USA Department of Stem Cell and Regenerative Biology Harvard UniversityCambridgeMA 02138USA Department of Pathophysiology Guangdong Provincial Key Laboratory of ProteomicsSchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouGuangdong 510515China Beijing Advanced Innovation Center for Genomics Department of Obstetrics and GynecologyThird HospitalSchool of Life SciencesPeking UniversityBeijing 100871China Biomedical Pioneering Innovation Center Center for Reproductive MedicineMinistry of EducationKey Laboratory of Cell Proliferation and DifferentiationBeijing 100871China Beijing Advanced Innovation Center for Genomics Department of Obstetrics and GynecologyThird HospitalSchool of Life SciencesPeking UniversityBeijing 100871China Beijing Advanced Innovation Center for Genomics Department of Obstetrics and GynecologyThird HospitalSchool of Life SciencesPeking UniversityBeijing 100871China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology Beijing 100191China Beijing Advanced Innovation Center for Genomics Department of Obstetrics and GynecologyThird HospitalSchool of Life SciencesPeking UniversityBeijing 100871China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology Beijing 100191China Key Laboratory of Assisted Reproduction Ministry of EducationBeijing 100191China Peking-Tsinghua Center for Life Sciences Peking UniversityBeijing 100871China Beijing Advanced Innovation Center for Genomics Department of Obstetrics and GynecologyThird HospitalSchool of Life SciencesPeking UniversityBeijing 1008

Proper development of fetal germ cells(FGCs)is vital for the precise transmission of genetic and epigenetic information through *** transcriptional landscapes of human FGC development have been revealed;however,the epigenetic reprogramming process of FGCs remains ***,we profiled the genome-wide DNA methylation and chromatin accessibility of human FGCs at different phases as well as gonadal niche cells at single-cell ***,we found that DNA methylation levels of FGCs changed in a temporal manner,whereas FGCs at different phases in the same embryo exhibited comparable DNA methylation levels and ***,we revealed the phase-specific chromatin accessibility signatures at the promoter regions of a large set of critical transcription factors and signaling pathway *** also identified potential distal regulatory elements including enhancers in ***,compared with other hominid-specific retrotransposons,SVA_D might have a broad spectrum of binding capacity for transcription factors,including SOX15 and ***,using an in vitro culture system of human FGCs,we showed that the BMP signaling pathway promoted the cell proliferation of FGCs,and regulated the WNT signaling pathway by orchestrating the chromatin accessibility of its ligand *** single-cell epigenomic atlas and functional assays provide valuable insights for understanding the strongly heterogeneous,unsynchronized,yet highly robust nature of human germ cell development.

关键词： Developmental biology Epigenetics

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ZNF280BY and ZNF280AY: Autosome derived Y-chromosome gene families in Bovidae

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BMC genomics 2011年第1期12卷 1-15页

作者： Yang, Yang Chang, Ti-Cheng Yasue, Hiroshi Bharti, Arvind K. Retzel, Ernest F. Liu, Wan-Sheng Department of Dairy and Animal Science The Center for Reproductive Biology and Health (CRBH) College of Agricultural Sciences The Pennsylvania State University University Park PA 16802 United States The Integrative Biosciences Program Bioinformatics and Genomics Option The Huck Institute of Life Sciences The Pennsylvania State University University Park PA 16802 United States National Institute of Agrobiological Sciences Tsukuba Ibaraki 305-0901 Japan National Center for Genome Resources Santa Fe NM 87505 United States Department of Pathology and Laboratory Medicine School of Medicine University of North Carolina-Chapel Hill Chapel Hill NC 27599 United States

Background: Recent progress in exploring the Y-chromosome gene content in humans, mice and cats have suggested that "autosome-to-Y" transposition of the male fertility genes is a recurrent theme during the mammalian Y-chromosome evolution. These transpositions are lineage-dependent. The purpose of this study is to investigate the lineage-specific Y-chromosome genes in ***: We took a direct testis cDNA selection strategy and discovered two novel gene families, ZNF280BY and ZNF280AY, on the bovine (Bos taurus) Y-chromosome (BTAY), which originated from the transposition of a gene block on the bovine chromosome 17 (BTA17) and subsequently amplified. Approximately 130 active ZNF280BY loci (and ~240 pseudogenes) and ~130 pseudogenized ZNF280AY copies are present over the majority of the male-specific region (MSY). Phylogenetic analysis indicated that both gene families fit with the "birth-and-death" model of evolution. The active ZNF280BY loci share high sequence similarity and comprise three major genomic structures, resulted from insertions/deletions (indels). Assembly of a 1.2 Mb BTAY sequence in the MSY ampliconic region demonstrated that ZNF280BY and ZNF280AY, together with HSFY and TSPY families, constitute the major elements within the repeat units. The ZNF280BY gene family was found to express in different developmental stages of testis with sense RNA detected in all cell types of the seminiferous tubules while the antisense RNA detected only in the spermatids. Deep sequencing of the selected cDNAs revealed that different loci of ZNF280BY were differentially expressed up to 60-fold. Interestingly, different copies of the ZNF280AY pseudogenes were also found to differentially express up to 10-fold. However, expression level of the ZNF280AY pseudogenes was almost 6-fold lower than that of the ZNF280BY genes. ZNF280BY and ZNF280AY gene families are present in bovid, but absent in other mammalian ***: ZNF280BY and ZNF280AY are lineage-speci

关键词： Autosomal Gene Bovine Testis Comparative Mapping Approach Male Fertility Gene Bovine Bacterial Artificial Chromosome

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Comprehensive genomic profiling of the lung transcriptome in emphysema and idiopathic pulmonary fibrosis using RNA-Seq

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BMC Proc 2012年第SUPPL 6期6卷 P21-P21页

作者： Rebecca L Kusko John Brothers, II Gang Liu Lingqi Luo Brenda Juan Guardela John Tedrow Yuriy Aleksyev Ivana V Yang Mick Correll Mark Geraci John Quackenbush Frank Sciurba Marc Lenburg David A Schwartz Jennifer Beane Naftali Kaminski Avrum Spira Genetics and Genomics Graduate Program Boston University School of Medicine Boston MA USA Bioinformatics Program Boston University Boston MA USA Division of Computational Biomedicine Department of Medicine Boston University School of Medicine Boston MA USA Simmons Center for Interstitial Lung Disease and Department of Medicine University of Pittsburgh Medical Center Pittsburgh PA USA Department of Pathology and Laboratory Medicine Boston University School of Medicine Boston MA USA Center for Genes Environment and Health and Department of Medicine National Jewish Health Denver CO USA Dana-Farber Cancer Institute and Harvard School of Public Health Boston MA USA Department of Medicine University of Colorado School of Medicine Aurora CO USA

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Targeting protein-protein interaction interfaces with antiviral N protein inhibitor in SARS-CoV-2

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Biophysical Journal 2024年第4期123卷 478-488页

作者： Hong, Jhen-Yi Lin, Shih-Chao Kehn-Hall, Kylene Zhang, Kai-Min Luo, Shun-Yuan Wu, Hung-Yi Chang, Sui-Yuan Hou, Ming-Hon Institute of Genomics and Bioinformatics and Department of Life Sciences National Chung Hsing University Taichung Taiwan Bachelor Degree Program in Marine Biotechnology College of Life Sciences National Taiwan Ocean University Keelung Taiwan Department of Biomedical Sciences and Pathobiology Virginia-Maryland College of Veterinary Medicine Virginia Polytechnic Institute and State University Blacksburg VA United States Center for Emerging Zoonotic and Arthropod-borne Pathogens Virginia Polytechnic Institute and State University Blacksburg VA United States Department of Chemistry National Chung Hsing University Taichung Taiwan Graduate Institute of Veterinary Pathobiology College of Veterinary Medicine National Chung Hsing University. Taichung Taiwan Department of Clinical Laboratory Sciences and Medical Biotechnology College of Medicine National Taiwan University Taipei Taiwan PhD Program in Medical Biotechnology National Chung Hsing University Taichung Taiwan Biotechnology Center National Chung Hsing University Taichung Taiwan

Coronaviruses not only pose significant global public health threats but also cause extensive damage to livestock-based industries. Previous studies have shown that 5-benzyloxygramine (P3) targets the Middle East respiratory syndrome coronavirus (MERS-CoV) nucleocapsid (N) protein N-terminal domain (N-NTD), inducing non-native protein-protein interactions (PPIs) that impair N protein function. Moreover, P3 exhibits broad-spectrum antiviral activity against CoVs. The sequence similarity of N proteins is relatively low among CoVs, further exhibiting notable variations in the hydrophobic residue responsible for non-native PPIs in the N-NTD. Therefore, to ascertain the mechanism by which P3 demonstrates broad-spectrum anti-CoV activity, we determined the crystal structure of the SARS-CoV-2 N-NTD:P3 complex. We found that P3 was positioned in the dimeric N-NTD via hydrophobic contacts. Compared with the interfaces in MERS-CoV N-NTD, P3 had a reversed orientation in SARS-CoV-2 N-NTD. The Phe residue in the MERS-CoV N-NTD:P3 complex stabilized both P3 moieties. However, in the SARS-CoV-2 N-NTD:P3 complex, the Ile residue formed only one interaction with the P3 benzene ring. Moreover, the pocket in the SARS-CoV-2 N-NTD:P3 complex was more hydrophobic, favoring the insertion of the P3 benzene ring into the complex. Nevertheless, hydrophobic interactions remained the primary stabilizing force in both complexes. These findings suggested that despite the differences in the sequence, P3 can accommodate a hydrophobic pocket in N-NTD to mediate a non-native PPI, enabling its effectiveness against various CoVs. © 2024 Biophysical Society

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Metformin escape in prostate cancer by activating the PTGR1 transcriptional program through a novel super-enhancer

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Signal Transduction and Targeted Therapy 2023年第9期8卷 4365-4379页

作者： Jianheng Ye Shanghua Cai Yuanfa Feng Jinchuang Li Zhiduan Cai Yulin Deng Ren Liu Xuejin Zhu Jianming Lu Yangjia Zhuo Yingke Liang Jianjiang Xie Yanqiong Zhang Huichan He Zhaodong Han Zhenyu Jia Weide Zhong Department of Urology Guangzhou First People’s HospitalSouth China University of Technology510180 GuangzhouGuangdongChina Urology Key Laboratory of Guangdong Province The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Medical University510230 GuangzhouGuangdongChina Guangzhou National Laboratory No.9 XingDaoHuanBei RoadGuangzhou International Bio Island510005 GuangzhouGuangdongChina Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences100700 BeijingChina Department of Botany and Plant Sciences University of CaliforniaRiversideCA 92507USA Graduate Program in Genetics Genomics&BioinformaticsUniversity of CaliforniaRiversideCA 92507USA State Key Laboratory of Quality Research in Chinese Medicine Macao University of Science and TechnologyTaipa999078 MacaoChina

The therapeutic efficacy of metformin in prostate cancer(PCa)appears uncertain based on various clinical *** treatment failure may be attributed to the high frequency of transcriptional dysregulation,which leads to drug ***,the underlying mechanism is still *** this study,we found evidences that metformin resistance in PCa cells may be linked to cell cycle ***-enhancers(SEs),crucial regulatory elements,have been shown to be associated with drug resistance in various *** analysis of SEs in metformin-resistant(MetR)PCa cells revealed a correlation with Prostaglandin Reductase 1(PTGR1)expression,which was identified as significantly increased in a cluster of cells with metformin resistance through single-cell transcriptome *** functional experiments showed that PTGR1 overexpression accelerated cell cycle progression by promoting progression from the G0/G1 to the S and G2/M phases,resulting in reduced sensitivity to ***,we identified key transcription factors that significantly increase PTGR1 expression,such as SRF and RUNX3,providing potential new targets to address metformin resistance in *** conclusion,our study sheds new light on the cellular mechanism underlying metformin resistance and the regulation of the SE-TFs-PTGR1 axis,offering potential avenues to enhance metformin’s therapeutic efficacy in PCa.

关键词： RUNX3 cancer offering

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BAG6 restricts pancreatic cancer progression by suppressing the release of IL33-presenting extracellular vesicles and the activation of mast cells

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Cellular & Molecular Immunology 2024年第8期21卷 918-931页

作者： Bilal Alashkar Alhamwe Viviane Ponath Fahd Alhamdan Bastian Dörsam Clara Landwehr Manuel Linder Kim Pauck Sarah Miethe Holger Garn Florian Finkernagel Anna Brichkina Matthias Lauth Dinesh Kumar Tiwari Malte Buchholz Daniel Bachurski Sabrina Elmshäuser Andrea Nist Thorsten Stiewe Lisa Pogge von Strandmann Witold Szymański Vanessa Beutgen Johannes Graumann Julia Teply-Szymanski Corinna Keber Carsten Denkert Ralf Jacob Christian Preußer Elke Pogge von Strandmann Institute for Tumor Immunology Philipps-University35043MarburgGermany Core Facility Extracellular Vesicles Philipps-University35043MarburgGermany Department of Anesthesiology Critical Careand Pain MedicineCardiac Anesthesia DivisionBoston Children’s HospitalBostonUSA Department of Immunology and Anaesthesia Harvard Medical SchoolBostonMAUSA Translational Inflammation Research Division&Core Facility for Single Cell Multiomics Philipps-University35043MarburgGermany Core Facility Bioinformatics Philipps-University35043MarburgGermany Clinic for Gastroenterology Endocrinology and MetabolismCenter for Tumor and Immune BiologyPhilipps-University35043MarburgGermany Institute of Systems Immunology Philipps-University35043MarburgGermany Cluster of Excellence on Cellular Stress Responses in Aging-Associated Diseases(CECAD) University of CologneCologneGermany Institute of Molecular Oncology and Genomics Core Facility Member of the German Center for Lung Research(DZL)Philipps-University35043MarburgGermany Institute of Lung Health Justus Liebig University35392GiessenGermany Institute of Translational Proteomics&Core Facility Translational Proteomics Biochemical/Pharmacological CentrePhilipps-University35043MarburgGermany Institute of Pathology Philipps-University Marburg and University Hospital Marburg(UKGM)MarburgGermany Department of Cell Biology and Cell Pathology Philipps-University35043MarburgGermany

Recent studies reveal a critical role of tumor cell-released extracellular vesicles(EVs)in pancreatic cancer(PC)***,driver genes that direct EV function,the EV-recipient cells,and their cellular response to EV uptake remain to be ***,we studied the role of Bcl-2-associated-anthanogene 6(BAG6),a regulator of EV biogenesis for cancer *** used a Cre recombinase/LoxP-based reporter system in combination with single-cell RNA sequencing to monitor in vivo EV uptake and tumor microenvironment(TME)changes in mouse models for pancreatic ductal adenocarcinoma(PDAC)in a Bag6 pro-or deficient *** vivo data were validated using mouse and human organoids and patient *** data demonstrated that Bag6-deficient subcutaneous and orthotopic PDAC tumors accelerated tumor growth dependent on EV ***,this was attributed to mast cell(MC)activation via EV-associated *** MCs promoted tumor cell proliferation and altered the composition of the TME affecting fibroblast polarization and immune cell *** cell proliferation and fibroblast polarization were mediated via the MC secretome containing high levels of PDGF and *** with high BAG6 gene expression and high protein plasma level have a longer overall survival indicating clinical *** current study revealed a so far unknown tumor-suppressing activity of BAG6 in ***6-deficiency allowed the release of EV-associated IL33 which modulate the TME via MC activation promoting aggressive tumor *** depletion using imatinib diminished tumor growth providing a scientific rationale to consider imatinib for patients stratified with low BAG6 expression and high MC infiltration.

关键词： Pancreatic cancer EVs BAG6 Mast cells

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Moving beyond gene expression: identification of lung-disease-associated novel transcripts and alternative splicing by RNA sequencing

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BMC Proceedings 2012年第6期6卷 1-2页

作者： John Brothers II Paola Sebastiani Marc Lenburg Avrum Spira Rebecca Kusko Yuriy Alekesyev Gang Liu Lingqi Luo Jennifer Beane Brenda Juan Guardela John Tedrow Frank Sciurba Naftali Kaminski Ivana V Yang David A Schwartz Mick Correll John Quackenbush Mark Geraci Bioinformatics Program Boston University Boston MA 02115 USA Genetics and Genomics Graduate Program Boston University School of Medicine Boston MA 02118 USA Department of Medicine Boston University School of Medicine Section of Computational Biomedicine Boston MA 02118 USA Department of Pathology and Laboratory Medicine Boston University School of Medicine Boston MA 02118 USA Simmons Center for Interstitial Lung Disease and Department of Medicine University of Pittsburgh Medical Center Pittsburgh PA 15213 USA Center for Genes Environment and Health and Department of Medicine National Jewish Health Denver CO 80206 USA Dana-Farber Cancer Institute and Harvard School of Public Health Boston MA 02115 USA Department of Medicine University of Colorado School of Medicine Aurora CO 80045 USA

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The cell surface marker CD36 selectively identifies matured,mitochondria-rich hPSC-cardiomyocytes

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细胞研究（英文版） 2020年第7期30卷 626-629页

作者： Ellen Ngar-Yun Poon Xiao-ling Luo Sarah E.Webb Bin Yan Rui Zhao Stanley Chun Ming Wu Yong Yang Peng Zhang Huajun Bai Jiaofang Shao Ching Man Chan Godfrey Chi-Fung Chan Suk Ying Tsang Rebekah L.Gundry Huang-Tian Yang Kenneth R.Boheler Department of Medicine and Therapeutics and Centre for Cardiovascular Genomics and Medicine The Chinese University of Hong Kong (CUHK) HKSAR China CAS Key Laboratory of Tissue Microenvironment and Tumor Laboratory of Molecular CardiologyShanghai Institute of Nutrition and Health University of Chinese Academy of Sciences (CAS) CAS Shanghai China Division of Life Science and State Key Laboratory of Molecular Neuroscience The Hong Kong University of Science and Technology HKSAR China Department of Computer Science The University of Hong Kong (HKU) HKSAR China Intervention and Cell Therapy Center Peking University Shenzhen Hospital Shenzhen China School of Life Sciences CUHK HKSAR China Department of Paediatrics and Adolescent Medicine HKU HKSAR China School of Biomedical Sciences HKU HKSAR China SUSTech Academy for Advanced Interdisciplinary Studies Southern University of Science and Technology (SUSTech) Shenzhen China Department of Bioinformatics School of Biomedical Engineering and InformaticsNanjing Medical University Nanjing Jiangsu China State Key Laboratory of Agrobiotechnology CUHK HKSAR China Department of Biochemistry and Center for Biomedical Mass Spectrometry Research Medical College of Wisconsin Milwaukee WIUSA CardiOmics Program Center for Heart and Vascular Research Division of Cardiovascular Medicine and Department of Cellular and Integrative Physiology University of Nebraska Medical Center Omaha NE USA Institute for Stem Cell and Regeneration Medicine CASBeijing China Division of Cardiology Department of Medicineand Department of Biomedical Engineering The Johns Hopkins University Baltimore MD USA

Dear Editor,Human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) are of significant translational value to in vitro studies of human cardiac development, drug and cardiotoxicity testing and cardiac disease *** of hPSCs to CMs,however, yields mixed cultures of atrial-, ventricular-, and pacemaker-like cells as well as non-CMs in variable proportions.1

关键词： Stem-cell differentiation Stem cells

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Identification of microRNA in the protist Trichomonas vaginalis

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genomics 2009年第5期93卷 487-493页

作者： Lin, Wei-Chen Li, Sung-Chou Lin, Wen-Chang Shin, Jyh-Wei Hu, Song-Nian Yu, Xiao-Min Huang, Ting-Yun Chen, Shih-Chieh Chen, Hua-Chien Chen, Shu-Jen Huang, Po-Jung Ruei-Chi Gan, Richie Chiu, Cheng-Hsun Tang, Petrus Molecular Regulation and Bioinformatics Laboratory Chang Gung University Taoyuan 333 Taiwan Division of Microbiology Graduate Institute of Biomedical Sciences Chang Gung University Taoyuan 333 Taiwan Institute of Biomedical Informatics National Yang-Ming University Taipei 112 Taiwan Taiwan International Graduate Program in Bioinformatics Academia Sinica Taipei 115 Taiwan Institute of Biomedical Sciences Academia Sinica Taipei 115 Taiwan Department of Parasitology National Cheng Kung University Tainan 701 Taiwan Key Laboratory of Genome Sciences and Information Beijing Institute of Genomics Chinese Academy of Sciences Beijing China Graduate University Chinese Academy of Sciences Beijing China Department of Life Sciences Chang Gung University Taoyuan 333 Taiwan Molecular Medicine Research Center Chang Gung University Taoyuan 333 Taiwan Bioinformatics Center Chang Gung University Tao-Yuan 333 Taiwan Chang Gung Molecular Infectious Diseases Research Center Chang Gung Memorial Hospital Taoyuan 333 Taiwan

MicroRNAs (miRNAs) are a class of small noncoding RNAs that have important regulatory roles in multicellular organisms. However, miRNA has never been identified experimentally in protist. Direct cloning of 438 expressed miRNA tags by microRNA serial analysis of gene expression from the parasitic protist Trichomonas vaginalis identified nine candidate miRNAs. bioinformatics analysis of the corresponding genomic region revealed that these miRNA candidates contain a classical stem-loop-stem structure of pre-microRNAs. Analysis of the 20 nt long mature tva-miR-001 showed that it is an intergenic miRNA located at the scaffold DS113596. Tva-miR-001 was differentially expressed in the trophozoite, pseudocyst and amoeboid stages. Based on the experimental results of the present study, we provided solid evidence that protist possesses a miRNA regulating network comparable with multicellular organisms for the first time. © 2009 Elsevier Inc. All rights reserved.

关键词： MicroRNA Protist Trichomonas vaginalis

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