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Bioinformatics analyses for signal transduction networks

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Science china(Life Sciences) 2008年第11期51卷 994-1002页

作者： LIU Wei1,2. LI dong2. ZHU YunPing2.& he {2.1,2.1 College of Mechanical & Electronic Engineering and Automatization, National University of Defense Technology, Changsha 410073, china 2.state key laboratory of proteomics, Beijing proteome research center, Beijing institute of {12. medicine, Beijing 102.06, china College of Mechanical & Electronic Engineering and Automatization National University of Defense Technology Changsha 410073 China

research in signaling networks contributes to a deeper understanding of organism living activities. With the development of experimental methods in the signal transduction field, more and more mechanisms of signaling pathways have been discovered. This paper introduces such popular bioin-formatics analysis methods for signaling networks as the common mechanism of signaling pathways and database resource on the Internet, summerizes the methods of analyzing the structural properties of networks, including structural Motif finding and automated pathways generation, and discusses the modeling and simulation of signaling networks in detail, as well as the research situation and tendency in this area. Now the investigation of signal transduction is developing from small-scale experiments to large-scale network analysis, and dynamic simulation of networks is closer to the real system. With the investigation going deeper than ever, the bioinformatics analysis of signal transduction would have immense space for development and application.

关键词： signal transduction structural motif automated pathways regeneration dynamics simulation

Multiomics analysis reveals metabolic subtypes and identifies diacylglycerol kinase α (DGKA) as a potential therapeutic target for intrahepatic cholangiocarcinoma

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Cancer Communications 2024年第2期44卷 226-250页

作者： Weiren Liu Huqiang Wang Qianfu Zhao Chenyang Tao Weifeng Qu Yushan Hou Run Huang Zimei Sun Guiqi Zhu Xifei {2. Yuan Fang Jun Gao Xiaoling Wu Zhixiang yang Rongyu Ping Jiafeng Chen Rui yang Tianhao Chu Jian Zhou Jia Fan Zheng Tang dong yang yinghong Shi Department of Liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityKey Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationShanghaiP.R.China research Unit of Liver cancer Recurrence and Metastasis Chinese Academy of Medical SciencesBeijingP.R.China state key {2. of Medical proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijingP.R.China

Background:Intrahepatic cholangiocarcinoma(iCCA)is a highly heteroge-neous and lethal hepatobiliary tumor with few therapeutic *** metabolic reprogramming of tumor cells plays an essential role in the develop-ment of tumors,while the metabolic molecular classification of iCCA is largely ***,we performed an integrated multiomics analysis and metabolic classification to depict differences in metabolic characteristics of iCCA patients,hoping to provide a novel perspective to understand and treat ***:We performed integrated multiomics analysis in 116 iCCA samples,including whole-exome sequencing,bulk RNA-sequencing and proteome *** on the non-negative matrix factorization method and the protein abundance of metabolic genes in human genome-scale metabolic models,the metabolic subtype of iCCA was *** and prognostic gene analy-ses were used to compare overall survival(OS)differences between metabolic *** proliferation analysis,5-ethynyl-2.-deoxyuridine(EdU)assay,colony formation assay,RNA-sequencing and Western blotting were performed to investigate the molecular mechanisms of diacylglycerol kinaseα(DGKA)in iCCA ***:Three metabolic subtypes(S1-S3)with subtype-specific biomarkers of iCCA were *** metabolic subtypes presented with distinct prog-noses,metabolic features,immune microenvironments,and genetic *** S2.subtype with the worst survival showed the activation of some special metabolic processes,immune-suppressed microenvironment and Kirsten ratsar-coma viral oncogene homolog(KRAS)/AT-rich interactive domain 1A(ARID1A)*** the S2.subtype-specific upregulated proteins,DGKA was further identified as a potential drug target for iCCA,which promoted cell proliferation by enhancing phosphatidic acid(PA)metabolism and activating mitogen-activated protein kinase(MAPK)***:Viamultiomics analyses,we identified three metabolic subtypes of iCCA,revealing

关键词： diacylglycerol kinaseα intrahepatic cholangiocarcinoma MAPK signaling metabolic classifi-cation multiomics analysis phosphatidic acid metabolism

一种基于基因表达模型识别酵母细胞周期条件特异调控子网的方法(英文)

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生物化学与生物物理进展 2010年第4期37卷 402-415页

作者：刘齐军王正华刘万霖李栋贺福初朱云平国防科学技术大学并行与分布处理国家重点实验室长沙410073 蛋白质组学国家重点实验室北京蛋白质组研究中心军事医学科学院放射与辐射医学研究所北京102206 复旦大学生物医学科学研究所上海200032

由高通量微阵列技术产生的数据集可以用于解释生物系统基因调控的未知机制.生物过程是动态的,所以很有必要关注某些条件下特异的基因调控子网络.细胞周期是一个基本的细胞过程,识别酵母的细胞周期特异调控子网是理解细胞周期过程的基础... 详细信息

由高通量微阵列技术产生的数据集可以用于解释生物系统基因调控的未知机制.生物过程是动态的,所以很有必要关注某些条件下特异的基因调控子网络.细胞周期是一个基本的细胞过程,识别酵母的细胞周期特异调控子网是理解细胞周期过程的基础,并且有助于揭示其他细胞条件的基因调控机理.使用一个基因表达微分方程模型(GEDEM),从静态网络中识别了动态的细胞周期相关调控关系.与已经报道的细胞周期相关调控相互作用相比,该方法识别了更多的真实存在的条件特异调控关系,取得了比当前的方法更好的性能.在大数据集上,GEDEM 识别了具有高敏感性和特异性的调控子网.组合调控的深入分析显示,条件特异调控子网的转录因子之间的相关性呈现出比静态网络中转录因子相关性更强,这说明条件特异网络比静态网络更加接近真实情况.另外,GEDEM 方法还识别更多潜在的共调控转录因子.

关键词：基因调控网络细胞周期基因表达模型条件特异子网微分方程模型

TCM-HIN2.ec:A strategy for uncovering biological basis of heart qi deficiency pattern based on network embedding and transcriptomic experiment

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Journal of Traditional Chinese Medical Sciences 2024年第3期11卷 264-274页

作者： Lihong Diao Xinyi Fan jiang Yu Kai Huang Edouard C.Nice Chao Liu dong Li Shuz{2.n Guo School of Traditional Chinese medicine Beijing University of Chinese MedicineBeijing 102488China Department of Biochemistry and Molecular Biology Monash UniversityClayton VIC 3800Australia Beijing institute of Lifeomics Beijing 102206China state key {2. of Medical proteomics Beijing 102206China National center for Protein Sciences(Beijing) Beijing 102206China Beijing proteome research {2. Beijing 102206China

Objective To elucidate the biological basis of the heart qi deficiency(HQD)pattern,an in-depth understanding of which is essential for improving clinical herbal *** We predicted and characterized HQD pattern genes using the new strategy,TCM-HIN2Vec,which involves heterogeneous network embedding and transcriptomic ***,a heterogeneous network of traditional Chinese medicine(TCM)patterns was constructed using public ***,we predicted HQD pattern genes using a heterogeneous network-embedding *** then analyzed the functional characteristics of HQD pattern genes using gene enrichment analysis and examined gene expression levels using ***,we identified TCM herbs that demonstrated enriched interactions with HQD pattern genes via herbal enrichment *** Our TCM-HIN2Vec strategy revealed that candidate genes associated with HQD pattern were significantly enriched in energy metabolism,signal transduction pathways,and immune ***,we found that these candidate genes were significantly differentially expressed in the transcriptional profile of mice model with heart failure with a qi deficiency ***,herbal enrichment analysis identified TCM herbs that demonstrated enriched interactions with the top 10 candidate genes and could potentially serve as drug candidates for treating *** Our results suggested that TCM-HIN2Vec is capable of not only accurately identifying HQD pattern genes,but also deciphering the basis of HQD *** our finding indicated that TCM-HIN2Vec may be further expanded to develop other patterns,leading to a new approach aimed at elucidating general TCM patterns and developing precision medicine.

关键词： Qi deficiency pattern heart failure Biological basis Network embedding Transcriptome

Exploration of Target Spaces in the Human Genome for Protein and Peptide Drugs

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Genomics, proteomics & Bioinformatics 2022年第4期20卷 780-794页

作者： Zhongyang Liu Honglei Li Zhaoyu Jin yang Li Feifei Guo yangzhige he Xinyue Liu Yaning Qi Liying Yuan fuchu he dong Li state key {2. of proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijing 102206China School of Basic Medical Sciences Anhui Medical UniversityHefei 230032China College of Chemistry and Environmental Science Hebei UniversityBaoding 071002China Suzhou Geneworks Technology Co. Ltd.Suzhou 215028China institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China Department of Medical research center Peking Union Medical College HospitalChinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100730China College of Life Sciences Hebei UniversityBaoding 071002China

After decades of development,protein and peptide drugs have now grown into a major drug class in the *** identification and validation are crucial for the discovery of protein and peptide drugs,and bioinformatics prediction of targets based on the characteristics of known target proteins will help improve the efficiency and success rate of target ***,owing to the developmental history in the pharmaceutical industry,previous systematic exploration of the target spaces has mainly focused on traditional small-molecule drugs,while studies related to protein and peptide drugs are ***,we systematically explore the target spaces in the human genome specifically for protein and peptide *** with other proteins,both successful protein and peptide drug targets have many special characteristics,and are also significantly different from those of small-molecule drugs in many *** on these features,we develop separate effective genome-wide target prediction models for protein and peptide ***,a user-friendly web server,Predictor Of Protein and Pept Ide drugs’therapeutic Targets(POPPIT)(http://***/),is established,which provides not only target prediction specifically for protein and peptide drugs but also abundant annotations for predicted targets.

关键词： Protein drug Peptide drug Target analysis Target prediction Web server

Plasma biomarker screening for liver fibrosis with the N-terminal isotope tagging strategy

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Science china(Life Sciences) 2011年第5期54卷 393-402页

作者： LI ShuLong LIU Xin WEI Lai WANG HuiFen ZHANG Jiyang WEI Handong QIAN XiaoHong {2. ying he fuchu state key {2. of proteomics Beijing Proteome Research Center Beijing Institute of Radiation Medicine Beijing 102206 China Beijing institute of Biotechnology Beijing 100071 China People 's Hospital of Peking University Beijing 100044 China 302.Military Hospital of china Beijing 100039 China institutes of Biomedical Sciences Fudan University Shanghai 200032 China Central laboratory Yantai Yu-Huang-Ding Hospital Yantai 264000 China

A non-invasive diagnostic approach is crucial for the evaluation of severity of liver disease,treatment decisions,and assessing drug *** study evaluated plasma proteomic profiling via an N-terminal isotope tagging strategy coupled with liquid chromatography/Fourier transform ion cyclotron resonance mass spectrometry measurement to detect liver fibrosis *** plasma from different liver fibrosis stages,which were assessed in advance by the current gold-standard of liver biopsy,was quantitatively analyzed.A total of 72.plasma proteins were found to be dysregulated during the fibrogenesis process,and this finding constituted a valuable candidate plasma biomarker bank for follow-up *** results of fibronectin by Western blotting reconfirmed the mass-based *** Pathways Analysis showed four types of metabolic networks for the functional effect of liver fibrosis disease in chronic hepatitis B ***,quantitative proteomics via the N-terminal acetyl isotope labeling technique provides an effective and useful tool for screening plasma candidate biomarkers for liver *** quantitatively monitored the fibrogenesis process in CHB *** discovered many new valuable candidate biomarkers for the diagnosis of liver fibrosis and also partly identified the mechanism involved in liver fibrosis *** results provide a clearer understanding of liver fibrosis pathophysiology and will also hopefully lead to improvement of clinical diagnosis and treatment.

关键词： quantitative proteomics fiver fibrosis biomarker plasma hepatitis B virus

General trends of protein expression and localization reveal the rule of bio-complexity realization

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General trends of protein expression and localization reveal...

A Yeast BiFC-seq Method for Genome-wide Interactome Mapping

第五届全国生物信息学与系统生物学学术大会暨国际生物信息学前沿研讨会高通量时代的生物信息学与系统生物学

作者：杨冬 Dingchen Li Fan Zhong dong Li {2. fuchu he state key {2. of proteomics Beijing Proteome Research CenterBeijing Institute of Radiation Medicine institutes of Biomedical Sciences and Department of Chemistry Fudan University

Background:During evolution,proteins containing newly emerged domains and the increasing proportion of multi-domain proteins in the full Genome-Encoded {2.(GEP) have substantially contributed to increasing biological ***,it is not known how these two potential structural factors are preferentially utilized at given physiological states,until our most recent study found that multidomain proteins or only older domain- containing proteins are significantly overrepresented in certain-state {2.s(CSPs,i.e., all the proteins expressed at certain physiological states) compared with GEP,which indicates biological complexity under certain conditions is more significantly realized by diverse domain organization than by the emergence of new types of *** further explore the regular utilization pattern in the view of protein spatial distribution at levels ranging from organelles to organs,we investigated the relationships between protein domain characters and protein subcelluar localization width(SLW) or tissue specificity(TS). Methods:To calculate SLW,we collected high confident subcellular location information in Swiss-Prot,GOA,human protein atlas(HPA),MitoP2.Human Liver Organelle {2.(HLOP) and related references and *** identification is based on RPS-BLAST against Pfam and SMART(Ehe number of OTCs (organ,tissue or cell types) in which the gene is expressed. Results:The integrated atlas contains subcellular localization information with high confidence of more than 13000 human proteins,including the subcellular locations for different splice isoforms as complete as *** on this atlas,we found that SLW positively correlates with DN value,while it negatively correlates with DA value,that is, multi-domain proteins or only older domain-containing proteins tend to be localized at more subcellular *** addition,SLW negatively correlate with TS,*** with more subcellular location

关键词： Biological complexity protein domain proteome subcellular localization tissue specificity

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Genomics, proteomics & Bioinformatics 2022年第4期20卷 795-807页

作者： Limin Shang Yuehui Zhang Yuchen Liu Chaozhi Jin Yanzhi Yuan Chunyan Tian Ming Ni Xiaochen Bo Li Zhang {2. Li fuchu he Jian Wang state key {2. of proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijing 102206China Department of Biotechnology Beijing Institute of Radiation MedicineBeijing 100850China Department of Rehabilitation medicine Nan LouKey Laboratory of Wound Repair and Regeneration of PLACollege of Life SciencesChinese PLA General HospitalBeijing 100853China School of Basic Medical Sciences Anhui Medical UniversityHefei 230032China

Genome-wide physical protein±protein interaction(PPI)mapping remains a major challenge for current ***,we reported a high-efficiency BiFC-seq method,yeastenhanced green fluorescent protein-based bimolecular fluorescence complementation(y EGFPBiFC)coupled with next-generation DNA sequencing,for interactome *** first applied y EGFP-BiFC method to systematically investigate an intraviral network of the Ebola ***-thirds(9/14)of known interactions of EBOV were recaptured,and five novel interactions were ***,we used the BiFC-seq method to map the interactome of the tumor protein *** identified 97 interactors of p53,more than three-quarters of which were ***,in a more complex background,we screened potential interactors by pooling two BiFC libraries together and revealed a network of 2.9 interactions among 2.5 *** results show that BiFC-seq is a highly sensitive,rapid,and economical method for genome-wide interactome mapping.

关键词： Bimolecular fluorescence complementation Protein–protein interaction High-throughput Next-generation sequencing

Dynamic landscape mapping of humoral immunity to SARS-CoY-2.identifies non-structural protein antibodies associated with the survival of critical COVID-19 patients

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Signal Transduction and Targeted Therapy 2021年第9期6卷 2843-2856页

作者： Linlin Cheng Xiaomei Zhang Yu Chen Dan Wang {2. Zhang Songxin Yan Hongye Wang Meng Xiao Te Liang Haolong Li Meng Xu Xin Hou jiayu Dai Xian Wu Mingyuan Li Minya Lu {2. Wu Ran Tian Jing Zhao Yan Zhang Wei Cao Jinglan Wang Xiaowei Yan Xiang Zhou Zhengyin Liu yingchun Xu fuchu he Yongzhe Li Xiaobo Yu Shuyang Zhang Department of Clinical laboratory State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijingChina state key {2. of proteomics Beijing Proteome Research CenterNational Center for Protein Sciences-Beijing(PHOENIX Center)Beijing Institute of LifeomicsBeijingChina

A comprehensive analysis of the humoral immune response to the severe acute respiratory syndrome coronavirus 2.SARS-CoV-2.is essential in understanding COVID-19 pathogenesis and developing antibody-based diagnostics and *** this work,we performed a longitudinal analysis of antibody responses to SARS-CoV-2.proteins in 104 serum samples from 49 critical COVID-19 patients using a peptide-based SARS-CoV-2.proteome *** data show that the binding epitopes of IgM and IgG antibodies differ across SARS-CoV-2.proteins and even within the same protein.

关键词： immunity antibodies patients