Platform-agnostic CellNet enables cross-study analysis of cell fate engineering protocols.
Platform-agnostic CellNet enables cross-study analysis of cell fate engineering protocols.
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DOI：
10.1016/j.stemcr.2023.06.008
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发表时间：
2023-08-08
影响因子：
5.9
通讯作者：
Cahan, Patrick
中科院分区：
文献类型：
--
作者：
Lo, Emily K. W.;Velazquez, Jeremy J.;Peng, Da;Kwon, Chulan;Ebrahimkhani, Mo R.;Cahan, Patrick
细胞工程方案的优化需要标准的、全面的质量指标。我们以前开发了CellNet，一种计算工具，用于定量评估工程细胞与其天然对应物相比的转录保真度，基于批量衍生的表达谱。然而，该平台和其他平台在比较来自不同来源的数据的能力方面受到限制，并且目前没有工具可以以标准化的方式轻松比较新协议与现有的最先进协议。在这里，我们利用我们之前应用的最高得分对变换来构建一个计算平台，平台无关的CellNet（PACNet），以解决这两个缺点。为了证明PACNet的实用性，我们将其应用于来自100多项研究的数千个样本，这些研究描述了数十种旨在产生七种不同细胞类型的协议。我们对肝细胞和心肌细胞方案进行了深入研究，以确定性能最佳的方法，表征方案内和实验室间变异的程度，并确定常见的脱靶特征，包括原发性肝源性类器官中令人惊讶的神经/神经内分泌特征。我们已经使PACNet作为一个易于使用的Web应用程序，允许用户评估他们的协议相对于我们的参考工程样品数据库，并作为开源，可扩展的代码。平台无关的CellNet量化工程细胞中的转录保真度PACNet允许比较不同的协议，对方法变化具有鲁棒性用户可以轻松地将查询数据与顶级细胞工程协议进行基准测试原代肝类器官表现出非预期的神经/神经内分泌特征Cahan和同事创建了一个易于使用的计算资源PACNet，用于工程细胞群体中转录保真度的平台无关评估，允许跨研究和跨协议基准测试。通过研究最先进的心肌细胞和肝细胞衍生方案，他们确定了心肌细胞工程中的两个独立步骤，这两个步骤最能增加心脏的特性，并发现了原发性肝源性类器官中的脱靶神经/神经内分泌特征，这可能反映了一种类似导管反应的过程。
Optimization of cell engineering protocols requires standard, comprehensive quality metrics. We previously developed CellNet, a computational tool to quantitatively assess the transcriptional fidelity of engineered cells compared with their natural counterparts, based on bulk-derived expression profiles. However, this platform and others were limited in their ability to compare data from different sources, and no current tool makes it easy to compare new protocols with existing state-of-the-art protocols in a standardized manner. Here, we utilized our prior application of the top-scoring pair transformation to build a computational platform, platform-agnostic CellNet (PACNet), to address both shortcomings. To demonstrate the utility of PACNet, we applied it to thousands of samples from over 100 studies that describe dozens of protocols designed to produce seven distinct cell types. We performed an in-depth examination of hepatocyte and cardiomyocyte protocols to identify the best-performing methods, characterize the extent of intra-protocol and inter-lab variation, and identify common off-target signatures, including a surprising neural/neuroendocrine signature in primary liver-derived organoids. We have made PACNet available as an easy-to-use web application, allowing users to assess their protocols relative to our database of reference engineered samples, and as open-source, extensible code. Platform-agnostic CellNet quantifies transcriptional fidelity in engineered cells PACNet allows comparison of diverse protocols, robust to method variations Users can easily benchmark query data against top cell engineering protocols Primary liver organoids exhibit an unintended neural/neuroendocrine signature Cahan and colleagues create an easy-to-use computational resource, PACNet, for platform-agnostic evaluation of transcriptional fidelity in engineered cell populations, allowing cross-study and cross-protocol benchmarking. Examining state-of-the-field cardiomyocyte and hepatocyte derivation protocols, they identify two independent steps in cardiomyocyte engineering that most increase cardiac identity and discover an off-target neural/neuroendocrine signature in primary liver-derived organoids, potentially reflecting a ductular reaction-like process.
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影响因子：
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作者：
Burridge PW;Holmström A;Wu JC
通讯作者：
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DOI：
10.1016/j.clinre.2018.03.009
发表时间：
2018-09
影响因子：
2.7
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10.1083/jcb.200311021
发表时间：
2004-07-05
期刊：
The Journal of cell biology
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影响因子：
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影响因子：
5.9
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通讯作者：
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