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Top-Down Vs. Bottom-Up 机理 • 自上而下与自下而上 基因表达特性与疾病发展 • Global Vs

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Top-Down Vs. Bottom-Up 机理 • 自上而下与自下而上 基因表达特性与疾病发展 • Global Vs 对完整人体进行测量和干预 Shanghai Jiao Tong UniversityTCM-Assess and intervene at whole body level The Power of Top-down Thinking and Top-downThe Shanghai Version of Systemsvs. Bottom-upBiology The four diagnostic techniques “四诊” • 望、闻、问、切 Gut Microbiota and Whole-body The eight guiding principles for Systems Biology differentiation of syndromes “八纲辨证” 肠道菌群与人体系统生物学 • 表里 • 寒热 • 虚实 Liping Zhao • 阴阳 Shanghai Center for Systems Biomedicine Room 3-517, Biology Building, Shanghai Jiao Tong 感官测量 经验判断 University, Shanghai 200240, China 中国上海市东川路800号上海交通大学生物楼3－517 赵立平 “模糊的”整体 Holistic but empirical 从基因的角度解释和防治疾病的分子医学 Shanghai Jiao Tong University Shanghai Jiao Tong University DNA vs. QI “氣” Gene-centric，molecular medicine TCM vs. Western Medicine 基因序列多样性与疾病易 • Diseased man vs. man’s disease 感性的关系 • 病的人与人的病 基因序列多样性与药物敏 • Stratification of patients vs. 感性的关系 classification of diseases 基因表达特性与药物代谢 • 病人分类与疾病分型 • Top-down vs. bottom-up 机理 • 自上而下与自下而上 基因表达特性与疾病发展 • Global vs. local 过程 • 整体到局部与局部到整体 ……….. • Intact person vs. Genes • 完整的人体与基因 定量测定 模式识别 精细的局部 Molecular detail at cellular level Molecular yet local but fragmentary at whole body level Complex systems share the same nature Complex systems share the same nature Shanghai Jiao Tong University 复杂系统在本质上都是相似的 Shanghai Jiao Tong University 复杂系统在本质上都是相似的 1，鲁棒性 Robustness“To understand or Homeostasis the whole, 2，功能冗余 FunctionalOne must redundancy study the whole” 3，整体调控要理解整体就必须研究整体 Global regulation 4，涌现特性 Emergent properties Engineering paradigm and TCM Engineering paradigm and TCM 工程学思维模式与中医理论 工程学思维模式与中医理论 Tools for understanding complex engineering systems can be applied in biomedicine Tools for understanding complex engineering systems can be applied in biomedicine Complex systems share the same nature 涌现特性测量与复杂系统分类和监测 Shanghai Jiao Tong University 复杂系统在本质上都是相似的 UnderstandingClassification and the monitoring behavior ofof complexcomplex systems systems based on measurements of emergent functions 1，鲁棒性 Robustness“To understand or Homeostasis the whole, Systems states and 2，功能冗余 FunctionalOne must redundancy study the whole” state space models 3，整体调控要理解整体就必须研究整体 • Structural state 结构状态 Functional state State space model Global regulation • 功能状态 状态空间模型 4，涌现特性 System trajectory Emergent properties analysis • Attractors 吸引子 Engineering paradigm and TCM Initial conditions 工程学思维模式与中医理论 • 起始条件 Tools for understanding complex engineering systems can be applied in biomedicine • Disturbances 扰动 System trajectory analysis 系统轨迹分析 Changes in vibration, noise and exhaust gas for Shanghai Jiao Tong University engine health monitoring 结构健康监测 Structural Health Monitoring 振动、噪声和尾气的模式变化与发动机健康监测 Emergent functions of the cell Shanghai Jiao Tong University 细胞的涌现特性 Classification and identification of complex systems based on the measurement of their emergent functions 基于涌现特性测量的复杂系统的 精细分类与鉴定 Secretome-extracellular proteins Vibration 振动 Classification in an unsupervised learning mode 分泌组－胞外蛋白质全谱 Noise 噪声 with no prior knowledge required Metabonome-extracellular metabolites 无监督的学习分类模式 代谢组－胞外代谢物全谱 Exhaust Gas 尾气 Nicholson 2004 Emergent functions of the human body 人体系统生物学与健康测量 Shanghai Jiao Tong University Shanghai Jiao Tong University 人体的涌现特性 (Whole-body systems biology and health assessment) 人体系统生物学通过在人体水平测定基因与环境互作的结果来准确评估 Metabonome 和监测人体的健康 Health assessment and monitoring based on measurements of results 代谢组 of gene-environment interactions at the whole-body level Metagenome 具有下列特征Essential criteria： • 非破坏性测量，可直接用于人体 元基因组 • Non-invasive • 整体测量，反映全身的健康状况 Secretome • Global • 高通量、低成本可实现大样本人群的动态监控 分泌组 • Dynamic, low-cost, high throughput • 以核酸、蛋白和代谢物等生物分子为测定对象 Urine-metabolites Vibration 振动 • Molecular-based 尿液代谢物谱 • 非靶向测定，通过“全谱扫描”和“盲分类”可以监测任何类型的健康变化 Feces-bacteria Noise 噪声 • Non-targeted 粪便细菌谱 • 数字化测量，可实现高度信息化 Blood-proteins Exhaust Gas 尾气 • Digital, quantitative, highly reproducible 血液蛋白质谱 人体健康的分子测量 MolecularShanghai Jiao Tong assessment University of human health at the whole-body level ——人体健康状况的多参数、多指标评估 分泌蛋白质组学 Systems approaches for Protein secretome quantitative assessment and 元基因组学 monitoring of human health Metagenome 代谢组学 用系统定量的方法进行 Metabonome on 人体健康状况的评价与监测 Primary Molecules ti a tr Secondary Molecules il n F io lut Di C R on e c s en o tr r atio Molecular Profiling and Covariation Analysis p n TMAO creatinine ti hippurate o allantoincreatininetaurine citrate n 全谱分子扫描技术与模式识别 hippurate urea water 2-oxoglutarate fumarate succinate 振动、噪声、尾气 ppm 7 6 5 4 3 2 1 与发动机健康监测 New view on human body Shanghai Jiao Tong University The Superorganism Concept * Cell composition of human *Joshua Lederberg body • 10％ human cells • 90％ bacterial cells Genome Gene composition of 基因组 Gut Microbiota and Whole- human body Foods • Human genome (25,000 食物 Health genes) body Systems Biology Drugs 健康 •Karyome 药物 • Mitochondrome • Microbiome Microbiome • 1000 species Liping Zhao 微生物组 • 1 million genes Shanghai Center for Systems Biomedicine • Diverse and active School of Life Science and Biotechnology metabolism Human microbiome- Shanghai Jiao Tong University the second genome acquired after birth 微生物组－人后天获得的第二个基因组 New view on human body Modulation of the second Shanghai Jiao Tong University The Superorganism Concept * Shanghai Jiao Tong University genome in the Superorganism Cell composition of human *Joshua Lederberg body • 10％ human cells • 90％ bacterial cells Genome Genome Genome 基因组 基因组 Gene composition of 基因组 human body Foods Health Foods Diseases 全基因组关联分析要包括肠道菌群的基因Foods 食物 健康 食物 疾病 • Human genome (25,000 食物 Health Whole-genomegenes) association studies should Drugs 健康 •Karyome 药物 • MitochondromeInclude our microbiome Microbiome Microbiome 微生物组 微生物组 • Microbiome Microbiome • 1000 species 微生物组 • 1 million genes • Diverse and active metabolism Human microbiome- Partner for health or Pathogen for diseases? the second genome acquired after birth 微生物组－人后天获得的第二个基因组 TCM works primarily via modulation of gut microbiota 肠道菌群其实一直就是中医药的主要作用靶点Shanghai Jiao Tong University Functional analysis of gut microbiota -Co-variation analysis between host global metabolism and gut microbiota Li et al. , PNAS Shanghai Jiao Tong University Shanghai Jiao Tong University Phylogenetic DGGE Band and Nearest Neighbour Correlation Metabolite linkage grouping Variable Shanghai Jiao Tong University http://www.upi.com/NewsTrack/Science/2008/02/06/study_maps_gut_microflora/6812/ 4-deoxyerythronate Bacteroidetes BAC-b16 Bacteroides thetaiotaomicron ---------------------------------------------------------------------------------------------- var97 AY895191, 100% citrate Study maps gut microflora 2,3-dihydroxybutyrate BAC-b31 Bacteroides uniformis var176 AB215084, 100% hippurate Published: Feb. 6, 2008 at 10:24 AM creatinine LONDON, Feb. 6 (UPI) -- A British-Chinese study has mapped the bacteria living in seven members of Bacteroides coprocola V3-b6 a Chinese family to determine the role of gut microbes in bodily processes. var25 AB200225, 100% dihydrothymine 4-hydroxyphenylacetylglycine V3-b24 Pseudobutyrivibrio ruminis The researchers from Imperial College London and China's Jiao Tong University said the makeup of var88 X95893, 100% 3-aminoisobutyrate each person's gut microflora influences their health, with abnormalities in gut microbes linked to taurine Clostridia CL-b11 bacterium mpn-isolate group25 diseases such as diabetes and obesity. var89 AF357573, 99% 3,5-hydroxybenzoate However, the relationship between different species of bacteria and different processes has previously dimethylamine CL-b8 Ruminococcus bromii been defined only at a broad level, the scientists said, noting that prior to their study, only five people var77 X85099, 100% lactate had had their gut microflora profiled in depth, with that data being published. CL-b16 Faecalibacterium prausnitzii ATCC27768, 2-hydroxyisobutyrate var128 AJ413954, 97% glycine "Now we have developed a new way of exploring the connections between bugs and man we can hope V3-b34 glycolate to find a 'Rosetta Stone' to translate the functional properties of the bugs and so improve therapies to Actinobacteria Faecalibacterium prausnitzii 1-88 var134 treat disorders of the gut and related conditions," said Imperial College London Professor Jeremy AY169430, 99% 4-hydroxyphenylacetate Nicholson, lead author of the study. CL-b14 Subdoligranulum variable BI-114 2-amino-3-hydroxyl-3-methylbutyrate var110 AJ518869, 97% 4-cresol sulfate The research, led by Professor Liping Zhao of Jiao Tong University in Shanghai, appears in the V3-b52 Bifidobacterium pseudocatenula guanodinoacetate Proceedings of the National Academy of Science. var211 D86187, 100% phenylacetylglutamine © 2008 United Press International. All Rights Reserved. This material may not be reproduced, redistributed, or manipulated in any form. Please click on the link below to view the entire article. http://www.upi.com/NewsTrack/Science/2008/02/06/study_maps_gut_microflora/6812/ Shanghai Jiao Tong UniversityHighlighted by Nature Review Microbiology Shanghai Jiao Tong UniversityHighlighted by Nature Review Microbiology http://www.upi.com/NewsTrack/Science/2008/02/06/study_maps_gut_microflora/6812/ http://www.upi.com/NewsTrack/Science/2008/02/06/study_maps_gut_microflora/6812/ ---------------------------------------------------------------------------------------------- ---------------------------------------------------------------------------------------------- Study maps gut microflora Study maps gut microflora Published: Feb. 6, 2008 at 10:24 AM Published: Feb. 6, 2008 at 10:24 AM LONDON, Feb. 6 (UPI) -- A British-Chinese study has mapped the bacteria living
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