NULISA: a proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing.
NULISA: a proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing.
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DOI：
10.1038/s41467-023-42834-x
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发表时间：
2023-11-09
影响因子：
16.6
通讯作者：
Ma, Xiao-Jun
中科院分区：
文献类型：
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作者：
Feng, Wei;Beer, Joanne C.;Hao, Qinyu;Ariyapala, Ishara S.;Sahajan, Aparna;Komarov, Andrei;Cha, Katie;Moua, Mason;Qiu, Xiaolei;Xu, Xiaomei;Iyengar, Shweta;Yoshimura, Thu;Nagaraj, Rajini;Wang, Li;Yu, Ming;Engel, Kate;Zhen, Lucas;Xue, Wen;Lee, Chen-jung;Park, Chan Ho;Peng, Cheng;Zhang, Kaiyuan;Grzybowski, Adrian;Hahm, Johnnie;Schmidt, Susanne V.;Odainic, Alexandru;Spitzer, Jasper;Buddika, Kasun;Kuo, Dwight;Fang, Lei;Zhang, Bingqing;Chen, Steve;Latz, Eicke;Yin, Yiyuan;Luo, Yuling;Ma, Xiao-Jun
血液蛋白质组为精准医学带来了巨大的希望，但由于大多数血浆蛋白质的低丰度和血浆蛋白质组的巨大动态范围，血液蛋白质组也带来了巨大的挑战。在这里，我们用核酸连接的免疫夹心测定（NULISA™）解决了这些挑战，该测定通过构建在抗肿瘤肽缀合抗体中的双重捕获和释放机制抑制测定背景，将传统邻位连接测定的灵敏度提高约10，000倍至阿摩尔水平。通过用未缀合的抗体减弱来自丰富靶标的信号和条形码报告DNA的下一代测序，实现了跨越宽动态范围的低丰度和高丰度蛋白质的高度多重定量。含有124种细胞因子和趋化因子以及其他蛋白质的200重NULISA在检测自身免疫性疾病和COVID-19患者中生物学上重要的低丰度生物标志物方面显示出对邻近延伸测定的上级灵敏度。全自动NULISA使广泛而深入的蛋白质组学分析易于用于研究和诊断应用。解锁血液蛋白质组需要高灵敏度和多路复用，以同时检测低丰度和高丰度蛋白质。在本文中，作者描述了一种具有阿托摩尔灵敏度的200重免疫测定法，用于检测炎症性疾病和COVID-19中的重要低丰度蛋白。
The blood proteome holds great promise for precision medicine but poses substantial challenges due to the low abundance of most plasma proteins and the vast dynamic range of the plasma proteome. Here we address these challenges with NUcleic acid Linked Immuno-Sandwich Assay (NULISA™), which improves the sensitivity of traditional proximity ligation assays by ~10,000-fold to attomolar level, by suppressing assay background via a dual capture and release mechanism built into oligonucleotide-conjugated antibodies. Highly multiplexed quantification of both low- and high-abundance proteins spanning a wide dynamic range is achieved by attenuating signals from abundant targets with unconjugated antibodies and next-generation sequencing of barcoded reporter DNA. A 200-plex NULISA containing 124 cytokines and chemokines and other proteins demonstrates superior sensitivity to a proximity extension assay in detecting biologically important low-abundance biomarkers in patients with autoimmune diseases and COVID-19. Fully automated NULISA makes broad and in-depth proteomic analysis easily accessible for research and diagnostic applications. Unlocking the blood proteome requires exquisite sensitivity and multiplexing to detect low and high abundance proteins simultaneously. Here the authors describe a 200-plex immunoassay with attomolar sensitivity to detect important low abundance proteins in inflammatory diseases and COVID-19.
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影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
3.7
作者：
Darmanis, Spyros;Nong, Rachel Yuan;Landegren, Ulf
通讯作者：
Landegren, Ulf
影响因子：
4.8
作者：
Hwang, Joseph;Banerjee, Munmun;Xiao, Qiang
通讯作者：
Xiao, Qiang
影响因子：
4.6
作者：
通讯作者：
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