Development of a proteomic signature associated with severe disease for patients with COVID-19 using data from 5 multicenter, randomized, controlled, and prospective studies.
Development of a proteomic signature associated with severe disease for patients with COVID-19 using data from 5 multicenter, randomized, controlled, and prospective studies.
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DOI：
10.1038/s41598-023-46343-1
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发表时间：
2023-11-20
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
通过疫苗的开发，在预防严重新冠肺炎疾病方面取得了重大进展。然而，对于感染SARS-CoV-2的门诊患者和住院患者，我们仍然缺乏有效的基线预测生物学特征来发展更严重的疾病。本研究的目的是通过5项国际门诊和住院试验和/或前瞻性队列研究，开发和外部验证一种新的基线蛋白质组特征，该特征通过对7,000种 + 蛋白的蛋白质组分析来预测新冠肺炎患者中或重度(VS轻度)疾病的发展。第二个目标是探索性的，以确定(1)个人基线蛋白质水平和/或(2)急性感染后前2周内与中/重度(VS轻度)疾病的发展相关的蛋白质水平变化。对于模型的开发，使用了从2个随机对照试验中收集的样本。分离血浆，并使用SomaLogic SomaScan平台来表征所有研究中感兴趣的7301种蛋白质的蛋白质水平。我们将113名患者分为轻度或中度/重度新冠肺炎病。弹性网络方法被用来开发可预测的蛋白质组特征。为了验证，我们将我们的签名应用于来自三个独立的前瞻性生物标记物研究的数据。我们发现，在对多重假设检验进行调整后，在基线测量的4,110种蛋白质在轻度新冠肺炎患者和中度/重度新冠肺炎患者之间存在显著差异。基线蛋白表达与预测的疾病严重程度相关，错误率为4.7%(AuC = 0.964)。我们还发现5种蛋白(Afamin、I-309、NKG2a、Pr57、Lipk)和患者年龄可以作为区分轻度新冠肺炎和中/重度新冠肺炎患者的标志，错误率为1.77%(AuC = 0.9804)。这个小组使用了3项外部研究的数据，分别是0.764(哈佛大学)、0.696(科罗拉多大学)和0.893(卡罗林斯卡学院)的AUC。在这项研究中，我们开发并外部验证了与疾病严重程度相关的基线新冠肺炎蛋白质组特征，用于门诊和住院新冠肺炎患者的潜在用途。
Significant progress has been made in preventing severe COVID-19 disease through the development of vaccines. However, we still lack a validated baseline predictive biologic signature for the development of more severe disease in both outpatients and inpatients infected with SARS-CoV-2. The objective of this study was to develop and externally validate, via 5 international outpatient and inpatient trials and/or prospective cohort studies, a novel baseline proteomic signature, which predicts the development of moderate or severe (vs mild) disease in patients with COVID-19 from a proteomic analysis of 7000 + proteins. The secondary objective was exploratory, to identify (1) individual baseline protein levels and/or (2) protein level changes within the first 2 weeks of acute infection that are associated with the development of moderate/severe (vs mild) disease. For model development, samples collected from 2 randomized controlled trials were used. Plasma was isolated and the SomaLogic SomaScan platform was used to characterize protein levels for 7301 proteins of interest for all studies. We dichotomized 113 patients as having mild or moderate/severe COVID-19 disease. An elastic net approach was used to develop a predictive proteomic signature. For validation, we applied our signature to data from three independent prospective biomarker studies. We found 4110 proteins measured at baseline that significantly differed between patients with mild COVID-19 and those with moderate/severe COVID-19 after adjusting for multiple hypothesis testing. Baseline protein expression was associated with predicted disease severity with an error rate of 4.7% (AUC = 0.964). We also found that five proteins (Afamin, I-309, NKG2A, PRS57, LIPK) and patient age serve as a signature that separates patients with mild COVID-19 and patients with moderate/severe COVID-19 with an error rate of 1.77% (AUC = 0.9804). This panel was validated using data from 3 external studies with AUCs of 0.764 (Harvard University), 0.696 (University of Colorado), and 0.893 (Karolinska Institutet). In this study we developed and externally validated a baseline COVID-19 proteomic signature associated with disease severity for potential use in both outpatients and inpatients with COVID-19.
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影响因子：
3.9
作者：
Orsucci D;Trezzi M;Anichini R;Blanc P;Barontini L;Biagini C;Capitanini A;Comeglio M;Corsini P;Gemignani F;Giannecchini R;Giusti M;Lombardi M;Marrucci E;Natali A;Nenci G;Vannucci F;Volpi G
通讯作者：
Volpi G
影响因子：
14.9
作者：
Chen J;Bardes EE;Aronow BJ;Jegga AG
通讯作者：
Jegga AG
影响因子：
9.3
作者：
Demichev V;Tober-Lau P;Lemke O;Nazarenko T;Thibeault C;Whitwell H;Röhl A;Freiwald A;Szyrwiel L;Ludwig D;Correia-Melo C;Aulakh SK;Helbig ET;Stubbemann P;Lippert LJ;Grüning NM;Blyuss O;Vernardis S;White M;Messner CB;Joannidis M;Sonnweber T;Klein SJ;Pizzini A;Wohlfarter Y;Sahanic S;Hilbe R;Schaefer B;Wagner S;Mittermaier M;Machleidt F;Garcia C;Ruwwe-Glösenkamp C;Lingscheid T;Bosquillon de Jarcy L;Stegemann MS;Pfeiffer M;Jürgens L;Denker S;Zickler D;Enghard P;Zelezniak A;Campbell A;Hayward C;Porteous DJ;Marioni RE;Uhrig A;Müller-Redetzky H;Zoller H;Löffler-Ragg J;Keller MA;Tancevski I;Timms JF;Zaikin A;Hippenstiel S;Ramharter M;Witzenrath M;Suttorp N;Lilley K;Mülleder M;Sander LE;PA-COVID-19 Study group;Ralser M;Kurth F
通讯作者：
Kurth F
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
5.4
作者：
Gold, Larry;Walker, Jeffrey J.;Williams, Stephen
通讯作者：
Williams, Stephen