Christner Martin, Dressler Dirk, Andrian Mark, Reule Claudia, Petrini Orlando
Department of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Biotesys GmbH, Esslingen, Germany.
PLoS One. 2017 Sep 6;12(9):e0182962. doi: 10.1371/journal.pone.0182962. eCollection 2017.
The fast and reliable characterization of bacterial and fungal pathogens plays an important role in infectious disease control and tracking of outbreak agents. DNA based methods are the gold standard for epidemiological investigations, but they are still comparatively expensive and time-consuming. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a fast, reliable and cost-effective technique now routinely used to identify clinically relevant human pathogens. It has been used for subspecies differentiation and typing, but its use for epidemiological tasks, e. g. for outbreak investigations, is often hampered by the complexity of data analysis. We have analysed publicly available MALDI-TOF mass spectra from a large outbreak of Shiga-Toxigenic Escherichia coli in northern Germany using a general purpose software tool for the analysis of complex biological data. The software was challenged with depauperate spectra and reduced learning group sizes to mimic poor spectrum quality and scarcity of reference spectra at the onset of an outbreak. With high quality formic acid extraction spectra, the software's built in classifier accurately identified outbreak related strains using as few as 10 reference spectra (99.8% sensitivity, 98.0% specificity). Selective variation of processing parameters showed impaired marker peak detection and reduced classification accuracy in samples with high background noise or artificially reduced peak counts. However, the software consistently identified mass signals suitable for a highly reliable marker peak based classification approach (100% sensitivity, 99.5% specificity) even from low quality direct deposition spectra. The study demonstrates that general purpose data analysis tools can effectively be used for the analysis of bacterial mass spectra.
快速、可靠地表征细菌和真菌病原体在传染病控制和追踪疫情爆发源方面发挥着重要作用。基于DNA的方法是流行病学调查的金标准,但它们仍然相对昂贵且耗时。基质辅助激光解吸/电离飞行时间质谱(MALDI-TOF MS)是一种快速、可靠且经济高效的技术,现在常用于鉴定临床上相关的人类病原体。它已被用于亚种分化和分型,但其在流行病学任务中的应用,例如疫情调查,常常受到数据分析复杂性的阻碍。我们使用一种用于分析复杂生物数据的通用软件工具,分析了德国北部一起大规模产志贺毒素大肠杆菌疫情中公开可用的MALDI-TOF质谱。该软件面临简化光谱和减少学习组规模的挑战,以模拟疫情爆发初期光谱质量差和参考光谱稀缺的情况。对于高质量的甲酸提取光谱,该软件内置的分类器仅使用10条参考光谱就能准确识别与疫情相关的菌株(灵敏度为99.8%,特异性为98.0%)。处理参数的选择性变化表明,在背景噪声高或人工减少峰计数的样本中,标记峰检测受损且分类准确性降低。然而,即使从低质量的直接沉积光谱中,该软件也始终能识别出适合基于高度可靠的标记峰分类方法的质量信号(灵敏度为100%,特异性为99.5%)。该研究表明,通用数据分析工具可有效地用于分析细菌质谱。