Molecular Systems Biology Peer Review Process File Single-cell Analysis of the Population Context Advances Rnai Screening at Multiple Levels Transaction Report
Molecular Systems Biology Peer Review Process File Single-cell Analysis of the Population Context Advances Rnai Screening at Multiple Levels Transaction Report
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分子系统生物学同行评审流程文件群体背景的单细胞分析推进多层次 Rnai 筛选交易报告
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L. Pelkmans
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作者：
B. Snijder;Raphael Sacher;Pauli Ramö;P. Liberali;K. Mench;N. Wolfrum;L. Burleigh;C. Scott;M. H. Verheije;J. Mercer;S. Moese;T. Heger;Kristina Theusner;Andreas Jurgeit;D. Lamparter;G. Balistreri;Mario Schelhaas;C. D. de Haan;V. Marjomäki;T. Hyypiä;P. Rottier;B. Sodeik;M. Marsh;J. Gruenberg;A. Amara;U. Greber;A. Helenius;L. Pelkmans
(Note注：除了更正可能引起歧义的排印或拼写错误外，信函和报告均未经编辑。信件和裁判报告的原始格式可能不会反映在本汇编中。再次感谢您将您的工作提交给分子系统生物学。我们已经收到了两位审稿人的回复，他们同意对你的手稿进行评估。正如你将从下面的报告中看到的，裁判#1是支持的，而裁判#2则要保守得多。我们同意审稿人#1的观点，即细胞群体异质性对RNAi表型筛选结果的影响是我们期刊读者潜在感兴趣的主题。Reynolds #2认为这项工作“对RNAi筛选社区有价值”，尽管由于专注于基于图像的表型测定，范围有些有限。总的来说，考虑到这些评估，并鉴于越来越多的已发表的基于图像的RNAi表型筛选，我们认为我们可以考虑对手稿进行重大修订。两位审查员提出的一个主要观点是，需要减少对结果的偏见，避免过度概括。因此，该研究可以以更中立的方式呈现，作为对群体异质性潜在影响的广泛测试，并以更平衡的方式报告结果（评审员#2：“更多关于他们的大多数数据显示的关于他们的假设的内容”）。因此，不是将基于背景的归一化作为一般工具呈现，该分析的主要结果之一可以是提供关于哪些情况/生物过程预期需要基于背景的归一化以及在哪些情况下该校正似乎不能解释所观察到的筛选/测定之间缺乏相关性的更深入的讨论。沿着同样的思路，分析如何
(Note: With the exception of the correction of typographical or spelling errors that could be a source of ambiguity, letters and reports are not edited. The original formatting of letters and referee reports may not be reflected in this compilation.) Thank you again for submitting your work to Molecular Systems Biology. We have now heard back from the two referees who accepted to evaluate your manuscript. As you will see from the reports below, referee #1 is supportive whereas referee #2 is much more reserved. We agree with reviewer #1 that the dissection of the impact of cell population heterogeneity on the outcome of RNAi phenotypic screens is a topic of potential interest to the readers of our journal. Referee #2 feels that the work "is of value to the RNAi screening community" albeit of somewhat limited scope due to the focus on image-based phenotypic assays. On balance, considering these evaluations and in view of the increasing number of published image-based RNAi phenotypic screens, we feel that we can consider a major revision of the manuscript. One of the major points raised by the two reviewers refers to the need of a less biased presentation of the results and avoid over-generalization. Thus, the study could be presented in a more neutral way as an extensive test of the potential impact of population heterogeneity and report the results in a much more balanced way (reviewer #2: "more forthcoming about what the majority of their data shows regarding their hypotheses"). Accordingly, rather than presenting context-based normalization as general tool, one of the major outcome of this analysis could be to provide a more in-depth discussion of which situations/biological processes are expected to require context-based normalization and in which situations this correction does not appear to explain the observed lack of correlations between screens/assays. Along the same lines, it would be important to analyze of how