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An ultrapotent RBD-targeted biparatopic nanobody neutralizes broad SARS-CoY-2 variants

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Signal Transduction and Targeted Therapy 2022年第3期7卷 780-789页

作者： Xiaojing Chi Xinhui Zhang Shengnan Pan Yanying Yu Yujin Shi Tianli Lin Huarui Duan Xiuying Liu Wenfang Chen Xuehua Yang Lan Chen Xiaoqian Dong Lili Ren Qiang Ding Jianwei Wang Wei Yang NHC Key Laboratory of systems biology of Pathogens Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical College100176 BeijingChina School of Medicine Tsinghua University100084 BeijingChina

The wide transmission and host adaptation of SARS-CoV-2 have led to the rapid accumulation of mutations,posing significant challenges to the effectiveness of vaccines and therapeutic *** several neutralizing antibodies were authorized for emergency clinical use,convalescent patients derived natural antibodies are vulnerable to SARS-CoV-2 Spike mutation.

关键词： neutral antibodies clinical

Author Correction: History and progress of hypotheses and clinical trials for Alzheimer’s disease

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Signal Transduction and Targeted Therapy 2019年第1期4卷 326-326页

作者： Pei-Pei Liu Yi Xie Xiao-Yan Meng Jian-Sheng Kang clinical systems biology laboratories The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052 HenanChina

Correction to:Signal Transduction and Targeted Therapy https://***/10.1038/s41392-019-0063-8,published online 23 August 2019 Since the publication of this Review Article,we noticed several mistakes in Table 2 and the Perspective section that need to be corrected *** Table 2,the status of AAB-003 Phase I trial is *** addition,the status of GV-971 Phase III trial is completed in *** correct portion of Table 2 is displayed as *** the perspective section,the sigma-1 receptor activator Anavex 2-73 has entered a phase III clinical trial but it was not granted fast-track status by the ***,the texts should be corrected to“In addition,fluoxetine can bind to the endoplasmic reticulum protein sigma-1 receptor.418 Sigma-1 receptor ligands can enhance acetylcholine secretion.

关键词： clinical Alzheimer corrected

A Novel DT40 Antibody Library for the Generation of Monoclonal Antibodies

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Virologica Sinica 2019年第6期34卷 641-647页

作者： Bei Wang Fei Wang He Huang Zhendong Zhao NHC Key Laboratory of systems biology of Pathogens Institute of Pathogen BiologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China clinical Immunology Center Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China CAMS-Oxford University International Center for Translational Immunology Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Early etiological diagnosis is very important for the control of sudden viral infections,and requires antibodies with both high sensitivity and high *** antibody preparation methods have limitations,such as a long and arduous cycle,complicated operation,and high expenses.A chicken lymphoma cell line,DT40,is known to produce IgM-type antibodies and undergo gene conversion and somatic mutation in the variable region of the immunoglobulin gene during ***,the DT40 cell line was developed to produce antibody libraries and prepare antibody rapidly in *** hypermutation in DT40 cells was regulated by the activation-induced cytidine deaminase(AID)gene,AID expression needs to be controlled to either fix the Ig sequence by stopping mutation or improve affinity by resuming mutation after the antibodies have been *** this study,we generated a novel AID-inducible DT40 cell line(DT40-H7),in which the endogenous AID gene was knocked out using the CRISPR/Cas9 genome editing system,and an inducible AID gene,based on the Tet-Off expression system,was stably *** expression was controlled in DT40-H7 cells in a simple and efficient manner;gene conversion and point mutations were observed only when AID was *** the antibody library generated from this cell line,we successfully obtained monoclonal antibodies against the NS1 protein of Zika *** DT40-H7 cell line represents a useful tool for the selection and evolution of antibodies and may also be a powerful tool for the rapid selection and generation of diagnostic antibodies for emerging infectious diseases.

关键词： Antibody library DT40 cell line Activation-induced cytidine deaminase(AID) Zika virus(ZIKV)

Genome-wide detection of additional fetal chromosomal abnormalities by cell-free DNA testing of 15,626 consecutive pregnant women

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Science China(Life Sciences) 2019年第2期62卷 215-224页

作者： Hong Yao Ya Gao Jia Zhao Rong Zhang Huixin Xu Huamei Hu Yanmei Luo Yuying Yuan Meili Fu Hongyun Zhang Hui Jiang Wei Wang Huanming Yang Jian Wang Zhiqing Liang Fang Chen Department of Gynecology & Obstetrics Southwest Hospital the Third Military Medical University BGI-Shenzhen China National GeneBank BGI-Shenzhen Birth Defect Screening Project Lab BGI-Shenzhen clinical laboratories of BGI Health BGI-Shenzhen James D.Watson Institute of Genome Sciences Laboratory of Genomics and Molecular Biomedicine Department of Biology University of Copenhagen

Cell-free DNA(cfDNA) testing for common fetal trisomies(T21, T18, T13) is highly effective. However, the usefulness of cfDNA testing in detecting other chromosomal abnormalities is unclear. We evaluated the performance of cfDNA testing for genome-wide abnormalities, and analyzed the incremental yield by reporting extra abnormalities. We performed genome-wide cfDNA testing in 15,626 consecutive pregnancies prospectively enrolled in this study. cfDNA testing results were reported and counseling was given depending on the presence of extra chromosomal abnormalities. cfDNA testing identified 190 cases(1.2%)of chromosomal abnormalities including 100 common trisomies and 90 additional abnormalities. By expanding the cfDNA reporting range to genome-wide abnormalities, the false positive rate increased to 0.39%(P<0.001) and positive predictive value(PPV) was reduced to 65.58%(P=0.42). However, the detection yield increased from 0.44% to 0.65%(P=0.014), and cfDNA testing detected 38.61%(39/101) additional abnormalities with no ultrasound and biochemical screening findings. cfDNA testing outperformed biochemical screening by showing 60 times higher true positive rate and fewer false negative ***-wide cfDNA testing significantly increased the diagnostic yield by detecting extra abnormalities, especially those without diagnostic indications. Genome-wide cfDNA testing has fewer false positive and false negative results compared with biochemical screening.

关键词： cell-free DNA genome-wide chromosomal abnormalities sensitivity specificity PPV

Translational Informatics for Parkinson’s Disease:from Big Biomedical Data to Small Actionable Alterations

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Genomics, Proteomics & Bioinformatics 2019年第4期17卷 415-429页

作者： Bairong Shen Yuxin Lin Cheng Bi Shengrong Zhou Zhongchen Bai Guangmin Zheng Jing Zhou Institutes for systems Genetics West China HospitalSichuan UniversityChengdu 610041China Center for systems biology Soochow UniversitySuzhou 215006China Center for Translational Biomedical Informatics Guizhou University School of MedicineGuiyang 550025China

Parkinson’s disease(PD)is a common neurological disease in elderly people,and its morbidity and mortality are increasing with the advent of global *** traditional paradigm of moving from small data to big data in biomedical research is shifting toward big data-based identification of small actionable *** highlight the use of big data for precision PD medicine,we review PD big data and informatics for the translation of basic PD research to clinical *** emphasize some key findings in clinically actionable changes,such as susceptibility genetic variations for PD risk population screening,biomarkers for the diagnosis and stratification of PD patients,risk factors for PD,and lifestyles for the prevention of *** challenges associated with the collection,storage,and modelling of diverse big data for PD precision medicine and healthcare are also *** perspectives on systems modelling and intelligent medicine for PD monitoring,diagnosis,treatment,and healthcare are discussed in the end.

关键词： Parkinson’s disease Healthcare Disease biomarker Translational informatics systems modelling

Embryo quality and chromosomal abnormality in embryos from couples undergoing assisted reproductive technology using preimplantation genetic screening

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Asian pacific Journal of Reproduction 2023年第1期12卷 16-22页

作者： Mina Niusha Seyed Ali Rahmani Leila Kohan Ladan Sadeghi Mohammad Nouri Hamid Reza Nejabati Department of biology Arsanjan BranchIslamic Azad UniversityArsanjanIran Department of Medical Genetics Tabriz University of Medical SciencesTabrizIran Department of Reproductive biology Faculty of Advanced Medical SciencesTabriz University of Medical Sciences TabrizIran Department of Biochemistry and clinical laboratories Faculty of MedicineTabriz University of Medical SciencesTabrizIran

Objective:To detect common chromosomal aneuploidy variations in embryos from couples undergoing assisted reproductive technology and preimplantation genetic screening and their possible associations with embryo ***:In this study,359 embryos from 62 couples were screened for chromosomes 13,21,18,X,and Y by fluorescence insitu *** biopsy of blastomere,a laser was used to remove a significantly smaller portion of the zona *** blastomere was gently biopsied by an aspiration pipette through the *** biopsy,the embryo was immediately returned to the embryo scope until *** integrity and blastocyst formation were assessed on day ***:Totally,282 embryos from 62 couples were *** chromosomes were normal in 199(70.57%)embryos and abnormal in 83(29.43%)*** was no significant association between the quality of embryos and numerical chromosomal abnormality(P=0.67).Conclusions:Embryo quality is not significantly correlated with its genetic ***,the quality of embryos determined by morphological parameters is not an appropriate method for choosing embryos without these abnormalities.

关键词： Assisted reproductive technology Preimplantation genetic screening Aneuploidy Fluorescence insitu hybridization Chromosomal abnormalities Embryo quality Blastomere Blastocyst

Diagnosing phenotypes of single-sample individuals by edge biomarkers

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Journal of Molecular Cell biology 2015年第3期7卷 231-241页

作者： Wanwei Zhang Tao Zeng Xiaoping Liu Luonan Chen Key Laboratory of systems biology Innovation Center for Cell Signaling NetworkInstitute of Biochemistry and Cell BiologyShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China

Network or edge biomarkers area reliable form to characterize phenotypes or ***,obtaining edges orcorrelations between molecules for an individual requires measurement ofmultiple samples of that individual,which are generally unavailable in clinical ***,it is strongly demanded to diagnose a disease by edge or network biomarkers in one-sample-for-one-individual ***,we developed a new computational framework,EdgeBiomarker,to integrate edge and node biomarkers to diagnose phenotype of each single test *** applying the method to datasets of lung and breast cancer,it reveals new marker genes/gene-pairs and related sub-networks for distinguishing earlier and advanced cancer *** method shows advantages over traditional methods:(i)edge biomarkers extracted from non-differentially expressed genes achieve better cross-validation accuracy of diagnosis than molecule or node biomarkers from differentially expressed genes,suggesting that certain pathogenic information is only present at the level of network and under-estimated by traditional methods;(ii)edge biomarkers categorize patients into low/high survival rate in a more reliablemanner;(iii)edge biomarkers are significantly enriched in relevant biological functions or pathways,implying that the association changes ina network,rather than expression changes in individual molecules,tendtobe causally related to cancer *** new frameworkof edgebiomarkers paves theway for diagnosing diseases and analyzing the irmolecular mechanisms by edges or networks in one-sample-for-one-individual *** also provides a powerful tool for precision medicine or big-data medicine.

关键词： edge biomarker edge feature progressive stages disease diagnosis big biological data

SIRT5 is important for bacterial infection by regulating insulin secretion and glucose homeostasis

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Protein & Cell 2020年第11期11卷 846-851页

作者： Cuiping Zhang Ke Wang Zuojian Hu Lujie Yang Bin Wei Shan Li Xue Qin Pengyuan Yang Hongxiu Yu Minhang Hospital Institutes of Blomedical Scliences Department of Systems Biology for MedicineSchool of Basic Medical SciencesFudan UniversityShanghai 200032China Department of clinical Laboratory First Afliated Hospital of Guangxi Medical UniversityNanning 530021China School of Life Science Shanghai UniversityShanghai 200444China Minhang Hospital Institutes of Biomedical Sciences Department of Systems Biology for MedicineSchool of Basic Medical SciencesFudan UniversityRoom 501Mingdao Building131 Dongan RoadShanghai 200032China Minhang Hospital Institutes of Biomedical Sciences Department of Systems Biology for MedicineSchool of Basic Medical SciencesFudan UniversityRoom 201Mingdao Building131 Dongan RoadShanghai 200032China

Dear Editor,Recent studies indicate that cellular metabolism plays a key role in supporting immune cell development,maintenance and function(Norata et al.,2015).For example,sensing of microbial ligands by macrophages triggers increased glucose metabolism,which delivers energy to support antimicrobial inflammation and the production of *** effect further enhances the generation of mitochondrial reactive oxygen species(ROS)to fight infections.

关键词： metabolism supporting homeostasis

Application of Nanopore Sequencing Technology in the clinical Diagnosis of Infectious Diseases

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Biomedical and Environmental Sciences 2022年第5期35卷 381-392页

作者： ZHANG Lu Lu ZHANG Chi PENG Jun Ping NHC Key Laboratory of systems biology of Pathogens Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100176China Key Laboratory of Respiratory Disease Pathogenomics Chinese Academy of Medical SciencesBeijing 100176China

Infectious diseases are an enormous public health burden and a growing threat to human health *** or classic recurrent pathogens,or pathogens with resistant traits,challenge our ability to diagnose and control infectious *** sequencing technology has the potential to enhance our ability to diagnose,interrogate,and track infectious diseases due to the unrestricted read length and system *** review focuses on the application of nanopore sequencing technology in the clinical diagnosis of infectious diseases and includes the following:(i)a brief introduction to nanopore sequencing technology and Oxford Nanopore Technologies(ONT)sequencing platforms;(ii)strategies for nanopore-based sequencing technologies;and(iii)applications of nanopore sequencing technology in monitoring emerging pathogenic microorganisms,molecular detection of clinically relevant drug-resistance genes,and characterization of disease-related microbial ***,we discuss the current challenges,potential opportunities,and future outlook for applying nanopore sequencing technology in the diagnosis of infectious diseases.

关键词： Nanopore sequencing Infectious diseases Pathogen Oxford Nanopore Technologies