Reproducible, high-dimensional imaging in archival human tissue by multiplexed ion beam imaging by time-of-flight (MIBI-TOF).

Reproducible, high-dimensional imaging in archival human tissue by multiplexed ion beam imaging by time-of-flight (MIBI-TOF).
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通过多路复用离子束飞行时间成像(MIBI-TOF)对存档人体组织进行可再现的高维成像。

DOI:
10.1038/s41374-022-00778-8
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发表时间:
2022-07
影响因子:
5
通讯作者:
Angelo, Michael
Angelo, Michael
中科院分区:
医学2区
文献类型:
--
作者:
Liu, Candace C.;Bosse, Marc;Kong, Alex;Kagel, Adam;Kinders, Robert;Hewitt, Stephen M.;Varma, Sushama;van de Rijn, Matt;Nowak, Stanislaw H.;Bendall, Sean C.;Angelo, Michael

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多路离子束飞行时间成像(MIBI-TOF)是质谱成像的一种形式,它使用金属标记的抗体和二次离子质谱法在同一组织切片中同时对数十种蛋白质进行成像。我们与美国国家癌症研究所(NCI)癌症免疫监测和分析中心(CIMAC)合作,进行了一项验证研究,评估了由21个样本组成的组织微阵列的十几个连续切片的一致性,这些样本经过独立处理并通过MIBI-TOF或单重免疫组织化学成像。(MHC)超过12天。在染色强度(R2 = 0.94 ± 0.04)和频率(R2 = 0.95 ± 0.04)方面,所有16个靶标的像素水平特征高度一致。与相邻连续切片的数字化单重免疫组化进行比较也显示出类似的一致性(R2 = 0.85 ± 0.08)。最后,八个细胞群的自动分割和聚类发现连续切片之间的细胞频率产生R2 = 0.94 ± 0.05的平均相关性。总而言之,我们证明,MIBI-TOF凭借经过严格审查的试剂和自动化分析,可以对档案人体组织中临床相关的细胞状态生成一致且定量的注释,并且更广泛地说,为基准测试多重免疫组化方法提供了一个可扩展的框架。
Multiplexed ion beam imaging by time-of-flight (MIBI-TOF) is a form of mass spectrometry imaging that uses metal labeled antibodies and secondary ion mass spectrometry to image dozens of proteins simultaneously in the same tissue section. Working with the National Cancer Institute’s (NCI) Cancer Immune Monitoring and Analysis Centers (CIMAC), we undertook a validation study, assessing concordance across a dozen serial sections of a tissue microarray of 21 samples that were independently processed and imaged by MIBI-TOF or single-plex immunohistochemistry (IHC) over 12 days. Pixel-level features were highly concordant across all 16 targets assessed in both staining intensity (R2 = 0.94 ± 0.04) and frequency (R2 = 0.95 ± 0.04). Comparison to digitized, single-plex IHC on adjacent serial sections revealed similar concordance (R2 = 0.85 ± 0.08) as well. Lastly, automated segmentation and clustering of eight cell populations found that cell frequencies between serial sections yielded an average correlation of R2 = 0.94 ± 0.05. Taken together, we demonstrate that MIBI-TOF, with well-vetted reagents and automated analysis, can generate consistent and quantitative annotations of clinically relevant cell states in archival human tissue, and more broadly, present a scalable framework for benchmarking multiplexed IHC approaches.
DOI: 10.1038/s41587-021-01094-0
发表时间: 2022-04
影响因子: 46.9
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Greenwald, Noah F.;Miller, Geneva;Moen, Erick;Kong, Alex;Kagel, Adam;Dougherty, Thomas;Fullaway, Christine Camacho;McIntosh, Brianna J.;Leow, Ke Xuan;Schwartz, Morgan Sarah;Pavelchek, Cole;Cui, Sunny;Camplisson, Isabella;Bar-Tal, Omer;Singh, Jaiveer;Fong, Mara;Chaudhry, Gautam;Abraham, Zion;Moseley, Jackson;Warshawsky, Shiri;Soon, Erin;Greenbaum, Shirley;Risom, Tyler;Hollmann, Travis;Bendall, Sean C.;Keren, Leeat;Graf, William;Angelo, Michael;Van Valen, David
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发表时间: 2020-01-01
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发表时间: 2014-04-01
期刊: NATURE METHODS
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DOI: 10.1126/sciadv.aax5851
发表时间: 2019-10-01
期刊: SCIENCE ADVANCES
影响因子: 13.6
作者:
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