TimeTeller: a New Tool for Precision Circadian Medicine and Cancer Prognosis

TimeTeller: a New Tool for Precision Circadian Medicine and Cancer Prognosis
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TimeTeller:精准昼夜节律医学和癌症预测的新工具

DOI:
10.1101/622050
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发表时间:
2019
期刊:
--
影响因子:
--
通讯作者:
Vlachou D
Vlachou D
中科院分区:
--
文献类型:
--
作者:
Vlachou D

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最近的研究证实,生物钟影响包括心脏病和癌症在内的许多疾病的发病、进展和治疗结果。然而,目前还没有工具来监测人体生物钟及其下游靶标的功能状态。我们提供了这样一种工具,并通过对乳腺癌的应用证明了它的临床意义,在乳腺癌中,我们发现总存活率和我们的时钟功能障碍的测量之间存在强烈的联系。我们使用机器学习方法并构建了一种名为TimeTeller的算法,该算法使用基因的多维状态对单个生物样本进行转录分析,以评估生物钟功能障碍的水平。我们展示了这如何区分健康和病变组织之间的差异,并证明时钟功能障碍指标是一种潜在的新的预后和预测乳腺癌的生物标记物,独立于主要已建立的预后因素。
Recent studies have established that the circadian clock influences onset, progression and therapeutic outcomes in a number of diseases including heart disease and cancer. There are, however, no tools to monitor the functional state of the circadian clock and its downstream targets in humans. We provide such a tool and demonstrate its clinical relevance by an application to breast cancer where we find a strong link between overall survival and our measure of clock dysfunction. We use a machine-learning approach and construct an algorithm called TimeTeller which uses the multi-dimensional state of the genes in a transcriptomics analysis of a single biological sample to assess the level of circadian clock dysfunction. We demonstrate how this can distinguish differences between healthy and diseased tissue and demonstrate that the clock dysfunction metric is a potentially new prognostic and predictive breast cancer biomarker that is independent of the main established prognostic factors.
DOI: --
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期刊:
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