Article(id=1211302346903122408, tenantId=1146029695717560320, journalId=1146031591421210625, issueId=1211302341744137007, articleNumber=null, orderNo=15, doi=10.3981/j.issn.1000-7857.2025.07.00054, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1751644800000, receivedDateStr=2025-07-05, revisedDate=1763654400000, revisedDateStr=2025-11-21, acceptedDate=1764000000000, acceptedDateStr=2025-11-25, onlineDate=1766726584411, onlineDateStr=2025-12-26, pubDate=1765555200000, pubDateStr=2025-12-13, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1767456000000, onlineIssueDateStr=2026-01-04, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1766726584411, creator=13701087609, updateTime=1774080361951, updator=sys-migrate, issue=Issue{id=1211302341744137007, tenantId=1146029695717560320, journalId=1146031591421210625, year='2025', volume='43', issue='23', pageStart='1', pageEnd='112', issueExtLink='null', onlineDate='null', pubDate='1765555200000', pubDateStr='2025-12-13', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1766726583181, creator='13701087609', updateTime=1774330548003, updator='13041195026', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1243195681876328676, tenantId=1146029695717560320, journalId=1146031591421210625, issueId=1211302341744137007, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1243195681876328677, tenantId=1146029695717560320, journalId=1146031591421210625, issueId=1211302341744137007, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=17, endPage=23, ext={EN=ArticleExt(id=1211302348526318073, articleId=1211302346903122408, tenantId=1146029695717560320, journalId=1146031591421210625, language=EN, title=Decoding the human phenome atlas: Unravelling the mystery of complex cross− phenotype associations and its underlying mechanisms, columnId=1157710593001177623, journalTitle=Science & Technology Review, columnName=Science and Technology News, runingTitle=null, highlight=null, articleAbstract=

Human phenomics research stands as the strategic high ground in the post−genomic era, and the launch of the International Human Phenome Project (IHPP) has garnered broad consensus within the global scientific community. The IHPP centers on the core scientific challenge of "delineating the associations and regulatory mechanisms between genes, phenotypes, and the environment, as well as between macro− and micro−phenotypes". Its primary objective is to establish the next−generation scientific "human phenome map" for life sciences and biomedicine. This ambitious vision has earned widespread recognition and enthusiastic support from the global scientific community. The paradigm of phenomics research is profoundly advancing the study of human health mechanisms and catalyzing a shift in healthcare models from a "disease−centric" to a "health−centric" approach. With the rapid development of precision phenotyping technologies and the deep integration with artificial intelligence, standardizing semantic identifiers, data governing, and establishing robust data−sharing ecosystems will emerge as pivotal challenges for future phenomics research.

, authors=null, authorsList=Han LIU, Guohui DING, authorCompany=null, correspAuthors=Guohui DING, authorNote=null, correspAuthorsNote=null, copyrightStatement=All rights reserved. Unauthorized reproduction is prohibited., copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1211302348916388366, articleId=1211302346903122408, tenantId=1146029695717560320, journalId=1146031591421210625, language=CN, title=解密生命全景图:人类表型组微观与整体的复杂关联及其机制解密, columnId=1150494642043760854, journalTitle=科技导报, columnName=科技评论, runingTitle=null, highlight=null, articleAbstract=

人类表型组研究是后基因组时代的战略制高点,开展国际人类表型组计划已成为国际学界共识。表型组学研究旨在通过跨尺度、多维度和贯穿全生命周期的精密表型测量,并对产生的大规模、多模态数据进行整合与系统性分析,从而揭示基因型−环境−表型之间以及不同尺度表型(如宏观表型与微观表型)之间的关联规律与互作机制。在精密测量与分析技术的推动下,表型组检测能力实现多维突破。国际人类表型组计划以“解析基因−表型−环境之间以及宏观−微观表型之间的关联与调控机制”为核心科学问题,其首要目标是绘制人类表型组参比图谱,为生命科学与生物医学构建新一代科研“导航图”。这一宏伟目标已获得国际科学界的普遍认同与积极响应。表型组研究范式正深刻推动人类健康机制研究,促进医疗保健模式从“以疾病为中心”向“以健康为中心”的变革。随着人类表型精密测量技术的快速发展与人工智能的深度融合,统一标识、数据治理及其共享生态建设,将成为未来表型组研究面临的关键挑战。

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刘晗,助理研究员,研究方向为生命健康领域技术趋势与发展战略,电子信箱:

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丁国徽(通信作者),研究员,研究方向为下一代生物数据设施关键技术、队列数据智能和科学驱动的全面健康,电子信箱:
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解密生命全景图:人类表型组微观与整体的复杂关联及其机制解密
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刘晗 1, 2 , 丁国徽 2, *
科技导报 | 科技评论 2025,43(23): 17-23
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解密生命全景图:人类表型组微观与整体的复杂关联及其机制解密
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刘晗,助理研究员,研究方向为生命健康领域技术趋势与发展战略,电子信箱:

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刘晗,助理研究员,研究方向为生命健康领域技术趋势与发展战略,电子信箱:

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刘晗1, 2 , 丁国徽2, *
作者信息
  • 1复旦大学人类表型组研究院,上海 201203
  • 2上海国际人类表型组研究院,上海 200433
通讯作者:
丁国徽(通信作者),研究员,研究方向为下一代生物数据设施关键技术、队列数据智能和科学驱动的全面健康,电子信箱:
Decoding the human phenome atlas: Unravelling the mystery of complex cross− phenotype associations and its underlying mechanisms
Han LIU1, 2 , Guohui DING2, *
Affiliations
  • 1Human Phenome Institute, Fudan University, Shanghai 201203, China
  • 2International Human Phenome Institutes (Shanghai), Shanghai 200433, China
出版时间: 2025-12-13 doi: 10.3981/j.issn.1000-7857.2025.07.00054
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人类表型组研究是后基因组时代的战略制高点,开展国际人类表型组计划已成为国际学界共识。表型组学研究旨在通过跨尺度、多维度和贯穿全生命周期的精密表型测量,并对产生的大规模、多模态数据进行整合与系统性分析,从而揭示基因型−环境−表型之间以及不同尺度表型(如宏观表型与微观表型)之间的关联规律与互作机制。在精密测量与分析技术的推动下,表型组检测能力实现多维突破。国际人类表型组计划以“解析基因−表型−环境之间以及宏观−微观表型之间的关联与调控机制”为核心科学问题,其首要目标是绘制人类表型组参比图谱,为生命科学与生物医学构建新一代科研“导航图”。这一宏伟目标已获得国际科学界的普遍认同与积极响应。表型组研究范式正深刻推动人类健康机制研究,促进医疗保健模式从“以疾病为中心”向“以健康为中心”的变革。随着人类表型精密测量技术的快速发展与人工智能的深度融合,统一标识、数据治理及其共享生态建设,将成为未来表型组研究面临的关键挑战。

人类表型组  /  国际人类表型组计划  /  科学健康

Human phenomics research stands as the strategic high ground in the post−genomic era, and the launch of the International Human Phenome Project (IHPP) has garnered broad consensus within the global scientific community. The IHPP centers on the core scientific challenge of "delineating the associations and regulatory mechanisms between genes, phenotypes, and the environment, as well as between macro− and micro−phenotypes". Its primary objective is to establish the next−generation scientific "human phenome map" for life sciences and biomedicine. This ambitious vision has earned widespread recognition and enthusiastic support from the global scientific community. The paradigm of phenomics research is profoundly advancing the study of human health mechanisms and catalyzing a shift in healthcare models from a "disease−centric" to a "health−centric" approach. With the rapid development of precision phenotyping technologies and the deep integration with artificial intelligence, standardizing semantic identifiers, data governing, and establishing robust data−sharing ecosystems will emerge as pivotal challenges for future phenomics research.

human phenome  /  International Human Phenome Project  /  scientific wellness
刘晗, 丁国徽. 解密生命全景图:人类表型组微观与整体的复杂关联及其机制解密. 科技导报, 2025 , 43 (23) : 17 -23 . DOI: 10.3981/j.issn.1000-7857.2025.07.00054
Han LIU, Guohui DING. Decoding the human phenome atlas: Unravelling the mystery of complex cross− phenotype associations and its underlying mechanisms[J]. Science & Technology Review, 2025 , 43 (23) : 17 -23 . DOI: 10.3981/j.issn.1000-7857.2025.07.00054
中国科学技术协会发布的2024重大科学问题、工程技术难题和产业技术问题中,“人类表型组微观与整体的复杂关联及其机制解密”入选十大前沿科学问题。表型(phenotype)是指基因和环境相互作用在生物体上产生的、可观察或测量的特征集合。表型组(phenome)是生物体从胚胎发育到出生、成长、衰老乃至死亡过程中,形态特征、功能、行为、分子组成规律等所有生物、物理和化学特征的集合[1]。人类表型组研究致力于精确测量人体各类表型,并通过综合分析,系统解构不同表型之间的复杂联系,构建表型关联网络,最终阐明基因−表型−环境之间,以及微观表型(如分子特征)与宏观表型(如器官功能、行为)之间的相互作用机制。作为后基因组时代的战略制高点与原始创新源,人类表型组研究的重要性已获学术界广泛认同。它不仅将引领生命科学研究范式的深刻变革,还将驱动生物医药产业实现新的突破。
人类基因组计划发现了大量疾病表型和遗传位点间的关联,为后续精准医学奠定了基础。随着分子生物学的发展,基因组序列、蛋白质特征、代谢物等纷纷被揭示,生命科学进入了后基因组时代,其首要目标是对生物系统的理解和阐释[2]。 2003年,学界提出表型检测方法在优化利用基因型数据方面存在不足,呼吁国际力量共建表型组数据库,深度整合表型组数据并开发新的分析方法[3-4]。此后,解析基因与表型间关联成为生命健康领域着力发展的方向。表型组研究被学界公认为是现阶段的科学研究重点领域之一,将带来巨大突破[5-6]
基因组与表型组之间具有复杂的调控网络关系,包括单基因调控、多效一因(即多个基因调控同一表型)和一因多效(即一个基因调控多个表型)等[7-8]。同时,表型组涵盖从微观到宏观的所有表型,涵盖转录、蛋白、代谢、细胞、器官、影像、环境、心理等多个层面。另外,表型组具有随着时空动态变化的特征,即伴随着生物体出生、成长发育到衰老死亡的整个生命周期,以及海拔、温度、湿度等环境变化而呈现出明显的动态变化。表型组学研究旨在通过跨尺度、多维度和贯穿全生命周期的精密表型测量,并对产生的大规模、多模态数据进行整合与系统性分析,从而揭示基因型−环境−表型之间以及不同尺度表型(如宏观表型与微观表型)之间的关联规律与互作机制。该研究领域构成了连接基因型与表现型的关键桥梁。
表型精密测量(deep phenotyping),即对表型精确和全面的分析,观察和描述表型的各个组成部分,提供更多特异性的数据[9]。基因和环境共同影响并产生正常和疾病表型,动态的生物网络和分子机制将基因组和环境信息与由此产生的表型联系起来[10]。相对于静态的人类遗传密码基因组,表型组则是动态的,是个体独特的基因组、生活方式和环境的综合。表型组补充了基因组的动态维度,是当前健康状况的衡量指标和未来疾病轨迹的预测指标。表型精密测量通过量化血液成分、肠道微生物组中微生物的组成和活性、数字健康测量(身体活动、睡眠质量、心率等)、认知评估、饮食摄入、环境暴露等,在推进医学知识方面具有更大的潜力[11-12]
精准医学的兴起对基因与表型的精确关系提出了要求。然而,当时表型研究仅应用于描述细胞、组织或生理环境等少数科研场景,而临床使用的表型描述不够精确,不能体现不同亚型疾病的不同表型,更不能用于预测治疗结果。表型精密测量以更个性和颗粒度更细的方式搜集人体详细信息,显著提升了表型数据的精确性和全面性。表型精密测量技术的发展与日益丰富的基因组数据相结合,展现出巨大的潜力[13]
在精密测量与分析技术的推动下,表型组检测能力实现多维突破。核磁共振(nuclear magnetic resonance,NMR)光谱、气相色谱(gas chromatography,GC)、液相色谱与质谱(mass spectrometry,MS)联用以及多元统计建模等化学分析和计算推动了代谢物、脂蛋白和糖蛋白等微观表型的检测,单光子发射断层扫描、正电子发射断层成像、正电子发射磁共振成像等多模态成像技术和可穿戴传感设备等带动了器官形态、生物学功能等宏观表型检测的发展。更多的表型被纳入人体表型精密测量中,例如,将语音作为生物标志物,能够及时检出心脏、肺、大脑、肌肉或声带等器官的异常,从而辅助诊断或风险预测[14]。同时,表型影像学通过整合X射线、超声、计算机断层扫描、正电子发射断层成像、磁共振成像等多种生物医学成像技术,将解剖结构、器官功能、细胞代谢等跨尺度特征转化为二维或三维可视化图像,成为贯穿宏观与微观表型的关键纽带[15]
中国科学界自2014年起就开始在“测一切之可测”理念指导下筹备发起人类表型组计划。2015年5月,“国际人类表型组研究”香山科学会议召开。金力、王辰、徐涛等院士在香山科学会议上率先提出系统开展人类表型组大科学计划的科学倡议,并成功吸引了“系统生物学之父”美国Leroy Hood与“代谢组学之父”英国Jeremy Nicholson成为国际人类表型组计划的联合发起人[16]。2016年5月,复旦大学在上海组织召开了“首届国际人类表型组大会”,多位国内外专家学者一致提议发起国际人类表型组计划,确定其核心任务是“解析基因−表型−环境之间以及宏观−微观表型之间的关联与调控机制”。2018年10月,复旦大学在上海主办“第二届国际人类表型组研讨会”,各国科学家就人类表型组国际大科学计划的实施路线图、合作机制与组织架构达成重要共识。来自17个国家20家机构的20位顶尖科学家组成了首届国际人类表型组研究协作组(International Human Phenome Consortium,IHPC)理事会,并一致同意启动人类表型组大科学计划的先导研究。这标志着人类表型组大科学计划正式由科学界先行启动。
IHPC致力于构建全球协同创新网络,加强大科学计划国际协同机制组织化建设,迄今已扩大至20个国家和地区的23个机构或团队,其中15个为各国院士团队。2020年,IHPC第2次理事会正式确定将国际协作组秘书处设于上海国际人类表型组研究院,设置“标准与技术规范”“知识产权数据共享与数据安全”和“伦理与法律社会问题”3个专业分委会,就人类表型组国际大科学计划的优先发展方向初步达成共识,认为近期应优先聚焦“新冠肺炎和其他重大疾病的表型组学研究”“表型组研究技术体系与科研基础设施构建”以及“表型组学研究中的标准操作程序”3大方向。2021年,在IHPC第3次理事会上,经过各国科学家的充分探讨与协商,就国际人类表型组计划下科研数据跨境共享与开放的基本原则,在兼顾安全和开放的前提下达成共识,鼓励各国科研团队通过科研实践探索国际科研合作与数据跨境共享的最佳实践[17]。2022年,在IHPC第4次理事会上,经过各国科学家的充分探讨与协商,就《人类表型组测量指南》和《共建全球人类表型组数据库倡议》达成共识[18]。《人类表型组测量指南》是为了适应人类表型组研究日趋增长的测量需求,达成人类表型组相关标准操作程序开发的框架指南,为编制相关人类表型组标准操作程序提供指导,保证不同机构间以基本一致的测量与科研操作流程,保障来自不同国家、机构、实验室平台的研究数据具有可比性,是进一步开展国际大科学计划的基础。《共建全球人类表型组数据库倡议》提出了共同建设全球性的人类表型组数据库及处理系统的宏大构想,倡议建设一个全球多中心的人类表型组数据汇集、管理、分发、协同平台——PhenoBank,为全球参与表型组研究的科学家提供服务,并为最终实现绘制全球性的人类表型组“导航图”目标提供平台与技术基础。PhenoBank试用版已于2024年上线,预计于2025年底正式向科研界开放使用[19]
“国际人类表型组计划”经过5年的布局与发展,中国核心团队已在基础科研领域奠定了引领优势,取得突破进展并达成4项国际领先成果。
一是建成全球首个跨尺度、多维度、一站式人类表型组精密测量平台。复旦大学已在张江复旦国际创新中心建成覆盖从微观的蛋白质组、代谢组、细胞到宏观的生物医学影像、人体外观、皮肤、睡眠、生物电、心理等23大类表型的全球首个跨尺度、多维度人类表型组精密测量中心,可一站式集成测量从宏观到微观多个尺度约3万个人类表型。二是完成第一个自然人群深度表型组千人队列,每个个体已测超过2.4万个表型指标,形成了数据总量达4.5 PB的表型组大数据,这是目前全球覆盖表型指标最多、规模最大的健康人群表型组学纵向队列。三是绘制第一张人类表型组导航图,发现150余万个表型之间的强关联,其中大部分关联是科学界首次发现,为表型组学研究提供了大量多维度、跨尺度的关联信息,从而指导新型表型调控机制的发掘与验证。四是研发了第一套多组学标准物质“中华家系1号”,获得多个国家一级标准物质认证,相关产品已被欧洲转化医学基础设施平台引进并使用,开创了生物医学“度量衡”新体系,为全球推进人类表型组计划奠定坚实的基础。
表型组学研究的全球协同创新,也为传统医学体系与生物医学前沿提供了深度交融机遇,为精准医学长期面临的系统性难题(疾病异质性解析、动态干预机制不明确、个体化治疗瓶颈等)开辟突破性路径。基于大型“证病结合”队列和人工智能(artificial intelligence,AI)技术,中医表型组学逐步形成研究体系[20]。通过整合中医临床证候队列与现代多组学技术(蛋白质组、代谢组、微生物组等),系统解码证候表征背后的分子网络机制及中药多靶点调控原理,进而推动疾病认知从单一器官病理分类向证候−表型组重构的范式跃迁。表型组学研究范式也正加速全球传统医学的现代化转型——印度阿育吠陀医学依托传统Prakriti体质分型系统,结合电子健康数据与无创诊断技术,实现了从疾病预测到个性化干预的循证闭环[21]。这2大传统医学体系与表型组学的协同创新,标志着从疾病治疗向健康维持转变的医学范式变革。
作为一种新兴的研究范式,表型组学研究纵向聚合了个体高通量信息,生成蛋白质组、代谢组、微生物组、暴露组、个体生活方式等多维度数据,通过量化血液成分、肠道微生物组中微生物的组成和活性、数字健康测量(身体活动、睡眠质量、心率等)、认知评估、饮食摄入、环境暴露等,结合创新算法已成功地用于人群健康的观测与干预。表型组学通过跨尺度动态监测与多层次数据整合,不仅为疾病发生机制提供了系统解析框架,更实现了对个体“健康−疾病”演化轨迹的精准追踪,从而为早期预警与预后干预奠定了融合技术创新与理论突破的整合性基础。区别于还原论范式,表型组学研究通过整合多组学、信息科学和数学等多学科的研究策略和方法,构建系统性研究框架,为解析生命复杂系统的生理与病理活动提供整体性检测与分析基础。
2012年,斯坦福大学综合个人组学分析的开创性研究首次将系统性表型组学应用于个体层面的健康与疾病综合分析,引起了生物医药领域的高度关注。该研究整合了全基因组测序、外显子组测序、血清代谢组学分析、外周血单核细胞相关分析、血清蛋白质组学分析以及临床实验室检测等多种技术,对受试者进行了长达14个月的系统性表型组数据记录和分析[22]。尤为重要的是,研究者动态记录了生活方式干预(减少糖摄入量、禁食、服用阿司匹林等)以及2次病毒感染引发的从健康到疾病的转化过程。该研究通过这种连续动态监测首次揭示,健康和疾病状态下分子和生物学网络存在显著的巨大变化。这一发现对疾病的早期诊断和精准治疗具有重要实践价值。
2014年,系统生物学研究所启动的包含基因组、肠道微生物、血液代谢物、血液蛋白质组、临床实验室检测和可穿戴设备等数据的前瞻性队列研究(“先锋100健康计划”)首次系统性验证了表型组学在捕捉健康向疾病状态转变并实施极早期干预以逆转疾病进程的潜力。这项研究计划共纳入108名健康受试者,通过整合基因组、蛋白质组、代谢组和肠道微生物组等多组学数据,结合持续9个月的实时活动与睡眠监测、医疗记录及生活习惯追踪,构建了动态更新的个人健康数据云平台[11]。研究采用跨尺度表型关联分析,识别出多组学数据间的相关性网络,并将其归类为不同功能的数据社区,进而精确定位了与生理状态及疾病风险相关的关键生物标志物及其在生物网络中的调控节点。例如,代谢物γ−谷氨酰酪氨酸被证实与心脏代谢疾病风险显著正相关。实现的重大理论突破是通过回溯分析参与者的血液样本,研究团队在临床症状出现前4年即检测到癌症相关分子网络的异常扰动,揭示了疾病潜伏期的早期生物学特征。该计划证实了表型组学的核心理论:对无症状健康个体进行深度表型全景测量,可动态解析健康−疾病的连续演化过程,为疾病预防与逆转提供关键时间窗口。基于个性化数据的行为干预成功改善了参与者分子水平的临床生物标志物(如血糖、炎症指标),优化个体健康状态成为可能。
此后,表型组学研究范式获得多领域专家的关注。心血管领域专家呼吁表型精密测量将为疾病患者治疗方案优化提供更精准依据,摆脱目前过度治疗的困境[23];口腔医学专家认为其在口腔疾病早期预防和诊断治疗中有重要作用[24];产科与儿科的研究结果也证实怀孕期间的母亲表型精密测量将为婴儿健康和妊娠结果改善提供机会[25]
在P4医学——预见性(predictive)、预防性(preventive)、个性化(personalized)以及参与性(participatory)的推动下,医疗保健正在经历从“以疾病为中心”向“以健康为中心”的范式转变 [26]。在此背景下,“科学健康”(scientific wellness)作为一种新颖的医疗保健理念应运而生。科学健康通过广泛收集人体生物数据并构建个体乃至人群健康检测和洞察体系,以制定个性化和可操作的策略,最终达到延长人类健康寿命的目标[27]
由“疾病为中心”向“健康为中心”的医疗变革得到了多国科技布局的支持。中国于2018年布局“精准医学研究”国家重点专项,支持了疾病精准分类和精准预防、大数据驱动的疾病风险预测以及健康管理咨询。英国政府持续资助英国生物样本库(UK Biobank),在其50万名参与者的基因组学数据基础上,推进蛋白质组学、影像表型等表型组数据,为研究疾病预防和健康促进提供了宝贵资源。英国启动了其规模最大的前瞻性健康研究项目“Our Future Health”,计划招募500万名成年志愿者,覆盖英国近10%的成年人口,旨在构建多维度健康信息库,推动对重大疾病早期检测、预防和个性化干预策略的研究,从而全面提升国民健康水平。美国的全民健康研究计划(All of US)致力于创建大规模志愿者队列,整合多组学数据,以识别疾病风险并制定个性化健康维护策略。美国投资5000亿美元用于支持美国的AI基础设施建设,为通用AI训练提供支持,而其关键应用场景之一正是医疗领域。随着全球科研加速向“科学智能”(AI for Science)范式转型,高质量人群生物数据集已成为驱动生命科学突破的战略性资源。
由于表型信息的复杂性,一些数据库在科研和医学领域已经提供了表型的标准化词汇、测量方法和算法等相关信息。在线人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)作为遗传疾病信息公共数据库,其每个条目虽包含遗传相关的表型信息,但这些信息以非结构化文本描述为主,不利于计算分析。于2007年上线的PhenX工具包(PhenX toolkit),旨在达成表型测量共识,提供了29个研究领域的900个测量协议,为研究人员提供经过验证、高质量且易实施的标准化方案。于2008年发布的人类表型本体(human phenotype ontology, HPO)由结构化表型词汇、疾病−表型关联注释以及基于这些表型的算法3部分组成,并将临床数据整合到转化研究中。然而,不同数据库、电子健康档案系统和科研机构在编码标准与术语系统上的不一致性长期存在,阻碍了表型数据的整合与比较,制约了利用全球多中心人群生物数据进行大规模分析的能力,并带来高昂的科研资源成本。
随着AI在生物医学领域的深度应用,对统一编码体系提出了迫切需求。近年来随着表型组学检测技术的不断发展,数据来源更加多样化,术语体系标准的缺失和数据格式的碎片化问题进一步凸显。AI的高效分析依赖于数据结构化与标准化,缺乏统一编码将导致AI训练模型缺乏有效的数据整合,降低准确性。统一术语的标准化数据集将避免大量数据清洗和术语映射,减少预处理成本,有效提升AI模式识别与决策优化。
表型组数据具有多维度、高复杂性、高通量、动态性、隐私性强等特征,为数据治理带来巨大的难度。队列研究以前瞻性设计、大样本追踪和多维表型组采集为核心优势,正深度驱动人群健康与疾病机制的解析进程。其产出的多维度生物数据已深度重塑生命科学的研究范式。随着单人表型组学数据呈指数级爆发,科研人员面临着高度异质化数据的应用困境。以UK Biobank为代表的超大规模人群队列展示了数据共享在解析复杂疾病与人类健康机制研究中的价值,也暴露出队列研究的地域性局限,即环境暴露、营养模式、文化因素等区域因素导致不同人群队列的生物标志物呈现显著差异,而其背后的分子机制更存在根本性分歧。这也给学界提出了关键问题:如何在海量数据集中精准识别高质量资源,避免陷入“数据沼泽”的沉没成本陷阱?
人群生物数据的全生命周期管理,从采集存储、清洗整合到跨境共享,涉及数10类参与主体与跨地区协作,其复杂性远超传统研究范式。当前,FAIR原则(可发现(findable)、可访问(accessible)、可互操作(interoperable)、可重用(reusable))作为全球数据治理的黄金标准,在理论层面构建了理想框架。但在人群生物数据这一人体数据的高度扩展数据集中,FAIR原则的实施依然面临诸多问题。数据中心、医院和研究机构使用各自的系统架构、数据格式、数据标准和网络安全协议,让多中心的数据共享难度很大。数据资源在访问和使用中需要明确数据的使用许可、协议和敏感信息的管理;不同来源数据的数据集中有效信息的抽取与跨系统集成依然互作难点;代码的可重用性依赖于计算环境和软件版本。深化FAIR原则的实施细则,通过术语映射、联邦学习与动态治理等构建数据治理框架,推进人群队列高质量数据集生产,是生命科学从“还原论”向“系统论”范式转型的核心挑战。
高质量人群生物数据资源及共享平台长期由欧美主导(如UK Biobank),其数据管理规范与分发体系亦多沿用欧美标准。中国近年来通过国家级重大专项支持,已建成多个大型人群队列数据库,逐步打破资源垄断格局。其中包括积累300万份生物样本的泰州队列、覆盖440万人的全球最大心血管病自然人群队列ChinaHEART队列,以及计划存储千万量级的中国自然人群生物资源库等。在生物资源库基础上积极建设国家级和区域级大型生物医学数据库,但尚未形成与英国UK Biobank(50万人规模,全球开放共享)同等国际影响力的综合性平台。
构建开放、协同、可持续的表型组数据共享生态,已成为全球表型组研究的核心挑战。为了迎接挑战,需要在技术层突破低成本高通量表型检测技术瓶颈,建立智能数据底座与跨模态知识图谱;在机制层构建机构间数据流通基础设施,创新数据贡献者激励与科研考评体系,并建立合规跨境数据流动框架;最终形成“贡献−共享−增值”的自驱型生态闭环。
  • 上海市科技重大专项(2023SHZDZX02)
  • 上海市科技创新项目(24DZ2307700)
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2025年第43卷第23期
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doi: 10.3981/j.issn.1000-7857.2025.07.00054
  • 接收时间:2025-07-05
  • 首发时间:2025-12-26
  • 出版时间:2025-12-13
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  • 收稿日期:2025-07-05
  • 修回日期:2025-11-21
  • 录用日期:2025-11-25
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上海市科技重大专项(2023SHZDZX02)
上海市科技创新项目(24DZ2307700)
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    1复旦大学人类表型组研究院,上海 201203
    2上海国际人类表型组研究院,上海 200433

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丁国徽(通信作者),研究员,研究方向为下一代生物数据设施关键技术、队列数据智能和科学驱动的全面健康,电子信箱:
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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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