对感染诊断的转录宿主反应特征进行基准测试。

IF 9 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Daniel G Chawla, Antonio Cappuccio, Andrea Tamminga, Stuart C Sealfon, Elena Zaslavsky, Steven H Kleinstein
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引用次数: 3

摘要

宿主转录反应特征的识别已成为感染诊断的新范式。对于临床应用,签名必须强大地检测感兴趣的病原体,而不会与意外条件交叉反应。为了评估传染病特征的表现,我们开发了一个框架,其中包括捕获传染性和非传染性条件的17,105个转录谱纲要,以及评估稳健性和交叉反应性的标准化方法。应用于30个已发表的感染签名,分析表明签名在检测独立数据中的病毒和细菌感染方面通常是稳健的。无症状和慢性感染也可检测到,尽管性能下降。然而,许多签名与意外感染和老化交叉反应。一般来说,我们发现健壮性和交叉反应性是相互冲突的目标,并且我们确定了与这种权衡相关的签名属性。在此开发的数据概要和评估框架为临床应用的签名开发提供了基础。本文的透明同行评议过程记录包含在补充信息中。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Benchmarking transcriptional host response signatures for infection diagnosis.

Benchmarking transcriptional host response signatures for infection diagnosis.

Benchmarking transcriptional host response signatures for infection diagnosis.

Benchmarking transcriptional host response signatures for infection diagnosis.

Identification of host transcriptional response signatures has emerged as a new paradigm for infection diagnosis. For clinical applications, signatures must robustly detect the pathogen of interest without cross-reacting with unintended conditions. To evaluate the performance of infectious disease signatures, we developed a framework that includes a compendium of 17,105 transcriptional profiles capturing infectious and non-infectious conditions and a standardized methodology to assess robustness and cross-reactivity. Applied to 30 published signatures of infection, the analysis showed that signatures were generally robust in detecting viral and bacterial infections in independent data. Asymptomatic and chronic infections were also detectable, albeit with decreased performance. However, many signatures were cross-reactive with unintended infections and aging. In general, we found robustness and cross-reactivity to be conflicting objectives, and we identified signature properties associated with this trade-off. The data compendium and evaluation framework developed here provide a foundation for the development of signatures for clinical application. A record of this paper's transparent peer review process is included in the supplemental information.

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来源期刊
Cell Systems
Cell Systems Medicine-Pathology and Forensic Medicine
CiteScore
16.50
自引率
1.10%
发文量
84
审稿时长
42 days
期刊介绍: In 2015, Cell Systems was founded as a platform within Cell Press to showcase innovative research in systems biology. Our primary goal is to investigate complex biological phenomena that cannot be simply explained by basic mathematical principles. While the physical sciences have long successfully tackled such challenges, we have discovered that our most impactful publications often employ quantitative, inference-based methodologies borrowed from the fields of physics, engineering, mathematics, and computer science. We are committed to providing a home for elegant research that addresses fundamental questions in systems biology.
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