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Single-cell transcriptomic analysis reveals dynamic alternative splicing and gene regulatory networks among pancreatic islets

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Science China(Life Sciences) 2021年第1期64卷 174-176页

作者： Yunjin Li Jiwei Chen Qiyue Xu Zebei Han Fei Tan Tieliu Shi Geng Chen center for bioinformatics and Computational Biology and Shanghai Key Laboratory of Regulatory BiologyInstitute of Biomedical SciencesSchool of Life SciencesEast China Normal UniversityShanghai200241China shanghai Skin Disease Hospital Anhui Medical UniversityShanghai200443China

Dear Editor,An increasing number of single-cell RNA-seq(scRNA-seq)studies gained deep insights into the gene expression heterogeneity among individual cells by cell type/state identification(Chen et al.,2019).Alternative splicing(AS)enables genes to generate multiple isoforms through the combination of disparate exons to increase the diversity of transcriptome(Lee and Rio,2015).

关键词： al. gained among

Characterization of a small-molecule inhibitor targeting NEMO/IKKβto suppress colorectal cancer growth

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Signal Transduction and Targeted Therapy 2022年第4期7卷 1219-1231页

作者： Zhenlong Yu Jian Gao Xiaolei Zhang Yulin Peng Wenlong Wei Jianrong Xu Zhenwei Li Chao Wang Meirong Zhou Xiangge Tian Lei Feng Xiaokui Huo Min Liu Mingliang Ye De-an Guo Xiaochi Ma Pharmaceutical Research center Second Affiliated HospitalDalian Medical UniversityDalian 116000China College of Pharmacy College(Institute)of Integrative MedicineDalian Medical UniversityDalian 116044China Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhou 221004China CAS Key Laboratory of Separation Sciences for Analytical Chemistry National Chromatographic R&A CenterDalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China shanghai Research center for Modernization of Traditional Chinese Medicine National Engineering Research Center for TCM Standardization TechnologyShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Academy of Integrative Medicine Shanghai University of Traditional Chinese Medicine1200 Cailun RoadShanghai 201203China Neurology Department Dalian University Affiliated Xinhua HospitalDalian 116021China

NEMO/IKKβcomplex is a central regulator of NF-κB signaling pathway,its dissociation has been considered to be an attractive therapeutic ***,using a combined strategy of molecular pharmacological phenotyping,proteomics and bioinformatics analysis,Shikonin(SHK)is identified as a potential inhibitor of the IKKβ/NEMO *** destabilizes IKKβ/NEMO complex with IC_(50) of 174 nM,thereby significantly impairing the proliferation of colorectal cancer cells by suppressing the NF-κB pathway in vitro and in *** addition,we also elucidated the potential target sites of SHK in the NEMO/IKKβ*** study provides some new insights for the development of potent small-molecule PPI inhibitors.

关键词： IKKβ colorectal cancer

Characterizing and annotating the genome using RNA-seq data

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Science China(Life Sciences) 2017年第2期60卷 116-125页

作者： Geng Chen Tieliu Shi Leming Shi center for Pharmacogenomics School of Pharmacy and School of Life SciencesFudan UniversityShanghai 201203China The center for bioinformatics and Computational Biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai 200241China State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology School of Life SciencesFudan UniversityShanghai 200433China Fudan-Zhangjiang center for Clinical Genomics Shanghai 201203China Zhangiiang centerfor Translational Medicine Shanghai 201203China

bioinformatics methods for various RNA-seq data analyses are in fast evolution with the improvement of sequencing technologies. However, many challenges still exist in how to efficiently process the RNA-seq data to obtain accurate and comprehensive results. Here we reviewed the strategies for improving diverse transcriptomic studies and the annotation of genetic variants based on RNA-seq data. Mapping RNA-seq reads to the genome and transcriptome represent two distinct methods for quantifying the expression of genes/transcripts. Besides the known genes annotated in current databases, many novel genes/transcripts(especially those long noncoding RNAs) still can be identified on the reference genome using RNA-seq. Moreover, owing to the incompleteness of current reference genomes, some novel genes are missing from them. Genome-guided and de novo transcriptome reconstruction are two effective and complementary strategies for identifying those novel genes/transcripts on or beyond the reference genome. In addition, integrating the genes of distinct databases to conduct transcriptomics and genetics studies can improve the results of corresponding analyses.

关键词： RNA序列基因组数据表征注释转录组学测序技术生物信息学数据分析

bioinformatics study indicates possible microRNA-regulated pathways in the differentiation of breast cancer

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Chinese Science Bulletin 2010年第10期55卷 927-936页

作者： PEI YunFei WANG ZhiMin FEI Fei SHAO ZhiMing HUANG Wei ZHANG XueGong MOE Key Laboratory of bioinformatics and bioinformatics Division TNLIST/Department of Automation Tsinghua University Beijing 100084 China Chinese National Human Genome center at shanghai Shanghai 201203 China Breast Cancer Institute Cancer Hospital Department of Oncology Shanghai Medical College Institutes of Biomedical Sciences Fudan University Shanghai 200032 China Department of Breast Surgery Cancer Hospital/Cancer Institute Breast Cancer Institute Fudan University Shanghai 200032 China

microRNAs (miRNAs) have been reported to be associated with the pathogenesis and progression of breast ***,little is known about the pathways through which miRNAs regulate these processes,e.g.,the interaction between miRNAs and their target genes with regard to different pathological status of breast cancer,such as histological *** study investigated the possible roles of miRNAs in the differentiation of histological grades of breast cancer with a computational *** on a microarray dataset,15 candidate miRNAs were identified,whose predicted target genes are enriched as differentially expressed between grade I and grade III breast *** them,9 key miRNAs focalize their target genes on 6 central signaling *** SMAD7 protein,the main inhibitory protein in the TGF-β pathway,is predicted as a target of several miRNAs and is also regulated by several other pathways that are possibly targeted by *** was hypothesized that miRNAs participate in the differentiation of breast cancer and the TGF-β pathway acts as a major implementary pathway on which several miRNAs take effect through multiple *** prediction power of the predicted miRNA target genes was validated on three independent *** differential expression of three miRNAs was validated by real-time PCR on breast carcinoma samples of 10 patients.

关键词：信号通路乳腺癌小分子RNA 生物信息学分化 miRNAs 转化生长因子-β 病理状态

Back to Science in Searching for SARS-CoV-2 Origins

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China CDC weekly 2023年第14期5卷 315-317页

作者： William J Liu Wenwen Lei Xiaozhou He Peipei Liu Qihui Wang Zhiqiang Wu Yun Tan Shuhui Song Gary Wong Jian Lu Jingkun Jiang Qiang Wei Mingkun Li Juncai Ma Xiaozhong Peng Yixue Li Baoxu Huang Yigang Tong Jun Han Guizhen Wu NHC Key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina CAS Key Laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijingChina NHC Key Laboratory of Systems Biology of Pathogens Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational MedicineRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Beijing Institute of Genomics Chinese Academy of Sciencesand China National Center for BioinformationBeijingChina Laboratory of Molecular Virology and Immunology Institut Pasteur of ShanghaiChinese Academy of SciencesShanghaiChina State Key Laboratory of Protein and Plant Gene Research Center for BioinformaticsSchool of Life SciencesPeking UniversityBeijingChina School of Environment Tsinghua UniversityBeijingChina National Pathogen Resource center Chinese Center for Disease Control and Prevention(China CDC)BeijingChina Microbial Resource and Big Data center Chinese National Microbiology Data Center(NMDC)Institute of MicrobiologyChinese Academy of SciencesBeijingChina State Key Laboratory of Medical Molecular Biology Department of Molecular Biology and BiochemistryInstitute of Basic Medical SciencesMedical Primate Research CenterNeuroscience CenterChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijingChina School of Life Science and Technology ShanghaiTech UniversityShanghaiChina Bio-Med Big Data center Key Laboratory of Computational BiologyCAS-MPG Partner Institute for Computational BiologyShanghai Institute of Nutrition and HealthUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghaiChina China Animal Health and Epidemiology center Qingdao CityShandong ProvinceChi

In recent decades,emerging and re-emerging human-infecting pathogens have been represented as huge threats to public health and have become a global concern(1).After outbreaks of two coronaviruses(CoVs),severe acute respiratory syndrome coronavirus(SARS-CoV)and Middle East respiratory syndrome coronavirus(MERS-CoV),severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)became the first-known pandemic hastening CoV with tremendous wrecking to the world(2).The origin tracing of these emerging pathogens is of great significance in infectious disease prevention and control(3–4).The origin of SARS-CoV-2 remains elusive after the more than 3-year pandemic,though scientists around the world are making great *** the experience of studying many other infectious pathogens,origin tracing is systematic and time-consuming *** supposed origins of many infectious pathogens are still in debate,including SARS-CoV and human immunodeficiency virus,etc(5).

关键词： prevention respiratory acute

Association between Alcohol, Smoking and HLA-DQA1*0201 Genotype in Psoriasis

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Acta Biochimica et Biophysica Sinica 2004年第9期36卷 597-602页

作者： Guang-Yong ZHENG1,2#, Sheng-Cai WEI3#, Tie-Liu SHI1, and Yi-Xue LI1* 1bioinformatics center, shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, shanghai 200031, China Research center for Proteome Analysis, Institute of Biochemistry and Cell Biology, shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, shanghai 200031, China 3Guangzhou Institute of Dermatology, Guangzhou 510095, China bioinformatics center Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Graduate School of the Chinese Academy of SciencesShanghai 200031 China Research center for Proteome Analysis Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Graduate School of the Chinese Academy of SciencesShanghai 200031 China Guangzhou Institute of DermatologyGuangzhou 510095 China

Psoriasis is a chronic skin disease triggered by genetic, environment or other risk factors such as infection, drugs, stress, moisture, alcohol, and smoking. A major psoriasis susceptibility locus at 6p21.3 has been identified. Further studies found that HLA-DQA1*0201 allele was associated with psoriasis. However, there were few data exploring an association between the environmental factors and susceptibility genes. In this study, the samples of 189 patients with psoriasis and 333 healthy controls were collected with their consent and were carried on analysis through polymerase chain reaction sequence-specific primer (PCR- SSP) method. The proportion of male psoriasis patients engaging in the smoking and alcohol was much higher than that of the control group (P6.91, P<1.0×10–4).

关键词： psoriasis HLA-DQA1*0201 allele smoking alcohol association

Antiviral Drugs(Synthetic Small Molecule Inhibitors and Nature Drugs)Against EV71 in Enteroviruses:Advances and Perspectives

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Clinical Complementary Medicine and Pharmacology 2023年第4期3卷 19-33页

作者： Yuwei Liu Yuan Xi Likai Ji Quan Shen Wen Zhang Mengzhu Xue Department of laboratory Medicine Department of Bioinformatics and Intelligent DiagnosisSchool of MedicineJiangsu UniversityZhenjiang 212003JiangsuChina SARI center for stem cell and nanomedicine Shanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201210China

Background:Enterovirus 71(EV71)is a major virus that causes hand-foot-mouth *** cases of infants and young children,EV71 infection has been associated with severe neurological disease and potentially fatal systemic *** sporadic outbreak worldwide is increasingly prevalent in the Asia-Pacific region,where it has become a major public health ***:No specific antiviral drugs are currently approved for the treatment of EV71 *** purpose of this study is to comprehensively review the research progress of anti-EV71 drugs(synthetic small molecule inhibitors and nature drugs)in the past twenty years,and further to promote the research and development of antiviral drugs against enterovirus ***:This study reviewed the drugs on anti EV71 in the past *** literature search in PubMed database was conducted for original studies and review articles on drugs against enterovirus *** articles published in English were selected for study and ***:As reviewed in this paper,bioactive molecules include receptor analogues,protease inhibitors,natural drugs derived from traditional chinese medicine or natural *** bioactive molecules have shown significant effectiveness in inhibiting the entry and replication of EV71 in vitro and in vivo ***:This review demonstrated that the entry receptor of EV71 into host cells has been studied,and receptor drugs against enterovirus have been made some progress,but most receptor analogues have not been *** research is needed in this area in the *** the other hand,the protease inhibitors have always been a major aspect of anti-enterovirus research and can be developed as antiviral agents for clinical *** terms of natural drugs,many monomers derived from traditional chinese medicine or natural medicine have good antiviral activity and little toxic and side effects on host cells,but in view of their multi-target prop

关键词： Hand-foot-mouth disease Enterovirus 71 Receptors Natural drugs Protease inhibitors

Enabling technology and core theory of synthetic biology

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Science China(Life Sciences) 2023年第8期66卷 1742-1785页

作者： Xian-En Zhang Chenli Liu Junbiao Dai Yingjin Yuan Caixia Gao Yan Feng Bian Wu Ping Wei Chun You Xiaowo Wang Tong Si Faculty of Synthetic Biology Shenzhen Institute of Advanced TechnologyShenzhen 518055China Institute of Synthetic Biology Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China National Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Frontiers Science center for Synthetic Biology and Key Laboratory of Systems Bioengineering(Ministry of Education) School of Chemical Engineering and TechnologyTianjin UniversityTianjin 300072China State Key Laboratory of Plant Cell and Chromosome Engineering Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Microbial Metabolism Shanghai Jiao Tong UniversityShanghai 200240China State Key Laboratory of Microbial Resources Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Tianjin Institute of Industrial Biotechnology Chinese Academy of SciencesTianjin 300308China Ministry of Education Key Laboratory of bioinformatics Center for Synthetic and Systems BiologyBioinformatics DivisionBeijing National Research Center for Information Science and TechnologyDepartment of AutomationTsinghua UniversityBeijing 100084China

Synthetic biology provides a new paradigm for life science research(“build to learn”)and opens the future journey of biotechnology(“build to use”).Here,we discuss advances of various principles and technologies in the mainstream of the enabling technology of synthetic biology,including synthesis and assembly of a genome,DNA storage,gene editing,molecular evolution and de novo design of function proteins,cell and gene circuit engineering,cell-free synthetic biology,artificial intelligence(AI)-aided synthetic biology,as well as *** also introduce the concept of quantitative synthetic biology,which is guiding synthetic biology towards increased accuracy and predictability or the real rational *** conclude that synthetic biology will establish its disciplinary system with the iterative development of enabling technologies and the maturity of the core theory.

关键词： synthetic biology quantitative synthetic biology genome synthesis and assembly DNA storage molecular evolution de novo design computer-aided design cell engineering gene circuit chassis cell artificial intelligent(AI) biofoundry

Predicting recurrence in osteosarcoma via a quantitative histological image classifier derived from tumour nuclear morphological features

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CAAI Transactions on Intelligence Technology 2023年第3期8卷 836-848页

作者： Zhan Wang Haoda Lu Yan Wu Shihong Ren Diarra mohamed Diaty Yanbiao Fu Yi Zou Lingling Zhang Zenan Wang Fangqian Wang Shu Li Xinmi Huo Weimiao Yu Jun Xu Zhaoming Ye Department of Orthopedic Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina Orthopedics Research Institute of Zhejiang University HangzhouChina Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province HangzhouChina Clinical Research center of Motor System Disease of Zhejiang Province HangzhouChina Institute for AI in Medicine School of Artificial IntelligenceNanjing University of Information Science&TechnologyNanjingChina Department of Pathology The Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina Department of Hematology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina bioinformatics Institute(BII) Agency for ScienceTechnology and Research(A*STAR)SingaporeSingapore

Recurrence is the key factor affecting the prognosis of ***,there is a lack of clinically useful tools to predict osteosarcoma *** application of pathological images for artificial intelligence‐assisted accurate prediction of tumour out-comes is ***,the present study constructed a quantitative histological image classifier with tumour nuclear features to predict osteosarcoma outcomes using haema-toxylin and eosin(H&E)‐stained whole‐slide images(WSIs)from 150 osteosarcoma *** first segmented eight distinct tissues in osteosarcoma H&E‐stained WSIs,with an average accuracy of 90.63%on the testing *** tumour areas were auto-matically and accurately acquired,facilitating the tumour cell nuclear feature extraction *** on six selected tumour nuclear features,we developed an osteosarcoma histological image classifier(OSHIC)to predict the recurrence and survival of osteo-sarcoma following standard *** quantitative OSHIC derived from tumour nuclear features independently predicted the recurrence and survival of osteosarcoma patients,thereby contributing to precision ***,we developed a fully automated workflow to extract quantitative image features,evaluate the diagnostic values of feature sets and build classifiers to predict osteosarcoma ***,the present study provides a novel tool for predicting osteosarcoma outcomes,which has a broad application prospect in clinical practice.

关键词： diseases learning(artificial intelligence) surgery tumours