The use of gene expression as a disease stratification tool of neonatal encephalopathy.
The use of gene expression as a disease stratification tool of neonatal encephalopathy.
复制标题
使用基因表达作为新生儿脑病的疾病分层工具。
DOI：
10.1038/s41390-020-1104-2
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发表时间：
2021
影响因子：
3.6
通讯作者：
Burgod C
中科院分区：
文献类型：
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作者：
Burgod C
我们祝贺Balada等人1在新生儿脑病（NE）中进行重要的转录组学研究。他们检查了信使核糖核酸(mRNA) 23个候选基因的表达在全血使用实时聚合酶链反应从24个婴儿与NE和34控制婴儿(1健康;33轻度polycythaemia),并在年龄< 6 h (n = 15 NE和2控制),12 h (n = 17 NE和1控制)、24小时(n = 18 NE和2控制),48 h (n = 14 NE和13控制),72 h (n = 13 NE和9控制),和96 h (n = 4 NE和7控制)。6个基因（MMP9、PPARG、IL8、HSPA1A、TLR8和CCR5）在新生儿和对照组婴儿之间具有区别性的图形模式，因此被选择用于后续的统计建模。虽然这是有用的信息，但我们想强调这些观察和方法的一些局限性。首先，使用仅由23个基因组成的预选小组可能会导致错误的结论，尤其是在初步研究中。通常，基于微阵列的基因表达研究的结果是不可重复的，当分析仅限于一小部分预先选择的基因时，观察到的差异的意义甚至更难解释。2其次，在6h内招募了两个对照，在12h内只招募了一个对照，这限制了前两个时间点对鉴别用于分析的差异表达基因的贡献。虽然我们承认招募对照婴儿对新生儿研究来说是一个重大挑战，但在出生后6小时内确定基因表达谱是至关重要的，因为新生儿神经保护干预的治疗窗口很窄，治疗需要在出生后几小时内开始才有成功的机会。最后，正如作者所声称的那样，这并不是关于基因表达在NE中的应用的第一篇报道。我们之前使用下一代测序方法报道了新生儿NE、健康对照组和败血症婴儿基因表达谱的差异。3,4为了说明这个问题，我们检查了Balada等人在之前发表的12个脑病婴儿和6个时间匹配的健康足月对照数据集中报道的6个基因的差异表达。我们使用线性混合效应模型来比较六个基因的表达
We congratulate Balada et al. 1 for pursuing important transcriptomic research in neonatal encephalopathy (NE). They examined the messenger RNA (mRNA) expression of 23 candidate genes in whole blood using real-time polymerase chain reaction from 24 babies with NE and 34 control babies (1 healthy; 33 with mild polycythaemia), and also at ages< 6 h (n= 15 NE vs. 2 controls), 12 h (n= 17 NE vs. 1 control), 24 h (n= 18 NE vs. 2 controls), 48 h (n= 14 NE vs. 13 controls), 72 h (n= 13 NE vs. 9 controls), and 96 h (n= 4 NE vs. 7 controls). Six genes (MMP9, PPARG, IL8, HSPA1A, TLR8, and CCR5) had a discriminant graphical pattern between babies with NE and control infants, and hence were selected for subsequent statistical modeling.While this is useful information, we would like to highlight some limitations of these observations and methodology. First, the use of a preselected panel of just 23 genes may lead to erroneous conclusions, particularly in preliminary studies. Often, the results of microarray-based gene expression studies are not reproducible, and when the analysis is limited to a small set of preselected genes, the significance of the observed differences is even more difficult to interpret. 2 Second, two controls were recruited within 6h and only one within 12h, which limited the contribution of the first two time points to the identification of the differentially expressed genes to be used for the analysis. While we acknowledge that recruitment of control infants represents a significant challenge for neonatal studies, the identification of a gene expression profile within 6 h of birth is pivotal since the therapeutic window for neonatal neuroprotective interventions is narrow, and treatments need to be initiated within hours after birth to have a chance of success. Finally, this is not the first report on use of gene expression in NE, as authors have claimed. We had previously reported differences in gene expression profiles of babies with NE, healthy control, and those with sepsis, using next-generation sequencing approach. 3, 4 To illustrate this issue, we examined the differential expression of the six genes reported by Balada et al. 1 in our previously published dataset of 12 encephalopathic babies and 6 time-matched healthy term controls. 3 We used linear mixedeffect models to compare the expression of the six genes