Evaluation of mRNA markers for estimating blood deposition time: Towards alibi testing from human forensic stains with rhythmic biomarkers
Evaluation of mRNA markers for estimating blood deposition time: Towards alibi testing from human forensic stains with rhythmic biomarkers
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DOI：
10.1016/j.fsigen.2015.12.008
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发表时间：
2016-03-01
影响因子：
3.1
通讯作者：
Kayser, Manfred
中科院分区：
文献类型：
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作者：
Lech, Karolina;Liu, Fan;Kayser, Manfred
确定生物痕迹留在犯罪现场的时间反映了法医调查的一个关键方面，因为如果可能的话，它将允许直接从痕迹证据中检验样本捐赠者的不在场证明，有助于将DNA鉴定的样本捐赠者与犯罪事件联系起来（或不联系）。然而，迄今为止还缺乏可靠且稳健的方法。在这项研究中，我们评估了mRNA的适用性，以估计血液沉积时间，其相对于褪黑激素和皮质醇，我们以前为此目的介绍了两种昼夜节律激素的附加值。通过分析21个候选mRNA标记物的血液样本从12个人收集的时钟在2小时的时间间隔为36小时，在现实生活中，控制条件下，我们确定了11个mRNA具有统计学显着的表达节奏。然后，我们使用这11个显著节律的mRNA标记物，在这些样本中分析了褪黑激素和皮质醇，建立了预测白天/夜晚时间类别的统计模型。我们发现，虽然在一般的mRNA为基础的估计时间类别是不准确的比基于mRNA的估计，使用三个mRNA标记物HSPA 1B，MKNK 2和PER 3与褪黑激素和皮质醇一般提高了时间预测的准确性相对于单独使用这两种激素。我们的数据最好地支持一个模型，通过使用这五种分子生物标志物估计三个时间类别，即夜间/清晨，上午/中午和下午/晚上，预测精度分别表示为AUC值为0.88，0.88和0.95。我们首次证明了mRNA对血液沉积时间的价值，并介绍了一种基于分子生物标志物估计白天/夜晚时间类别的统计模型，该模型将在未来用其他样本进一步验证。此外，我们的工作提供了新的线索的分子方法的死亡时间估计使用显着节奏的mRNA标记在这里建立。(C)2015爱思唯尔爱尔兰有限公司版权所有。
Determining the time a biological trace was left at a scene of crime reflects a crucial aspect of forensic investigations as - if possible - it would permit testing the sample donor's alibi directly from the trace evidence, helping to link (or not) the DNA-identified sample donor with the crime event. However, reliable and robust methodology is lacking thus far. In this study, we assessed the suitability of mRNA for the purpose of estimating blood deposition time, and its added value relative to melatonin and cortisol, two circadian hormones we previously introduced for this purpose. By analysing 21 candidate mRNA markers in blood samples from 12 individuals collected around the clock at 2 h intervals for 36 h under real-life, controlled conditions, we identified 11 mRNAs with statistically significant expression rhythms. We then used these 11 significantly rhythmic mRNA markers, with and without melatonin and cortisol also analysed in these samples, to establish statistical models for predicting day/night time categories. We found that although in general mRNA-based estimation of time categories was less accurate than hormone-based estimation, the use of three mRNA markers HSPA1B, MKNK2 and PER3 together with melatonin and cortisol generally enhanced the time prediction accuracy relative to the use of the two hormones alone. Our data best support a model that by using these five molecular biomarkers estimates three time categories, i.e. night/early morning, morning/noon, and afternoon/evening with prediction accuracies expressed as AUC values of 0.88, 0.88, and 0.95, respectively. For the first time, we demonstrate the value of mRNA for blood deposition timing and introduce a statistical model for estimating day/night time categories based on molecular biomarkers, which shall be further validated with additional samples in the future. Moreover, our work provides new leads for molecular approaches on time of death estimation using the significantly rhythmic mRNA markers established here. (C) 2015 Elsevier Ireland Ltd. All rights reserved.