A pipeline that integrates the discovery and verification of plasma protein biomarkers reveals candidate markers for cardiovascular disease.
A pipeline that integrates the discovery and verification of plasma protein biomarkers reveals candidate markers for cardiovascular disease.
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DOI：
10.1038/nbt.1899
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发表时间：
2011-06-19
影响因子：
46.9
通讯作者：
Carr, Steven A.
中科院分区：
文献类型：
--
作者：
Addona, Terri A.;Shi, Xu;Keshishian, Hasmik;Mani, D. R.;Burgess, Michael;Gillette, Michael A.;Clauser, Karl R.;Shen, Dongxiao;Lewis, Gregory D.;Farrell, Laurie A.;Fifer, Michael A.;Sabatine, Marc S.;Gerszten, Robert E.;Carr, Steven A.
我们开发了一条管道，将从发现到血浆生物标记物鉴定验证阶段使用的蛋白质组技术整合在一起，并应用它从接受治疗性、计划性心肌梗死(PMI)治疗肥厚型心肌病的患者的血液中识别心脏损伤的早期生物标记物。在受控心肌损伤之前、期间和之后直接从患者心脏采集血液确保了候选生物标记物的丰富，并允许患者作为自己的生物对照。LC-MS/MS分析检测到121种高度差异表达的蛋白质，包括先前已证实的心血管疾病标记物和心肌梗死(MI)的>；100新候选生物标记物。准确的包涵体质量筛选(AIMS)基于外周血浆中高度特异的靶向检测，包括一些如果没有这一步骤就不太可能被识别的标记，从而限定了候选对象的子集。用定量多反应监测质谱仪或免疫分析法对正常对照和PMI或自发性MI患者的外周血浆进行分析表明，候选生物标志物可能是MI的特异性生物标志物。这项研究表明，现代蛋白质组技术，当连贯地整合时，可以产生新的心血管生物标记物，值得在大型、不同种类的队列中进一步评估。
We developed a pipeline to integrate the proteomic technologies used from the discovery to the verification stages of plasma biomarker identification and applied it to identify early biomarkers of cardiac injury from the blood of patients undergoing a therapeutic, planned myocardial infarction (PMI) for treatment of hypertrophic cardiomyopathy. Sampling of blood directly from patient hearts before, during and after controlled myocardial injury ensured enrichment for candidate biomarkers and allowed patients to serve as their own biological controls. LC-MS/MS analyses detected 121 highly differentially expressed proteins, including previously credentialed markers of cardiovascular disease and >100 novel candidate biomarkers for myocardial infarction (MI). Accurate inclusion mass screening (AIMS) qualified a subset of the candidates based on highly specific, targeted detection in peripheral plasma, including some markers unlikely to have been identified without this step. Analyses of peripheral plasma from controls and patients with PMI or spontaneous MI by quantitative multiple reaction monitoring mass spectrometry or immunoassays suggest that the candidate biomarkers may be specific to MI. This study demonstrates that modern proteomic technologies, when coherently integrated, can yield novel cardiovascular biomarkers meriting further evaluation in large, heterogeneous cohorts.
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影响因子：
15.8
作者：
Faca VM;Song KS;Wang H;Zhang Q;Krasnoselsky AL;Newcomb LF;Plentz RR;Gurumurthy S;Redston MS;Pitteri SJ;Pereira-Faca SR;Ireton RC;Katayama H;Glukhova V;Phanstiel D;Brenner DE;Anderson MA;Misek D;Scholler N;Urban ND;Barnett MJ;Edelstein C;Goodman GE;Thornquist MD;McIntosh MW;DePinho RA;Bardeesy N;Hanash SM
通讯作者：
Hanash SM
影响因子：
9.3
作者：
Abbatiello SE;Mani DR;Keshishian H;Carr SA
通讯作者：
Carr SA
影响因子：
37.8
作者：
Knight, C;Kurbaan, AS;Sigwart, U
通讯作者：
Sigwart, U
DOI：
10.1142/s0219720005001375
发表时间：
2005-08-01
影响因子：
1
作者：
Futschik, Matthias E.;Carlisle, Bronwyn
通讯作者：
Carlisle, Bronwyn
影响因子：
13.6
作者：
Rhee, Eugene P.;Souza, Amanda;Gerszten, Robert E.
通讯作者：
Gerszten, Robert E.