Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA.
BMC Bioinformatics. 2010 Jul 20;11:384. doi: 10.1186/1471-2105-11-384.
All infectious disease oriented clinical diagnostic assays in use today focus on detecting the presence of a single, well defined target agent or a set of agents. In recent years, microarray-based diagnostics have been developed that greatly facilitate the highly parallel detection of multiple microbes that may be present in a given clinical specimen. While several algorithms have been described for interpretation of diagnostic microarrays, none of the existing approaches is capable of incorporating training data generated from positive control samples to improve performance.
To specifically address this issue we have developed a novel interpretive algorithm, VIPR (Viral Identification using a PRobabilistic algorithm), which uses Bayesian inference to capitalize on empirical training data to optimize detection sensitivity. To illustrate this approach, we have focused on the detection of viruses that cause hemorrhagic fever (HF) using a custom HF-virus microarray. VIPR was used to analyze 110 empirical microarray hybridizations generated from 33 distinct virus species. An accuracy of 94% was achieved as measured by leave-one-out cross validation.
VIPR outperformed previously described algorithms for this dataset. The VIPR algorithm has potential to be broadly applicable to clinical diagnostic settings, wherein positive controls are typically readily available for generation of training data.
目前所有针对传染病的临床诊断检测方法都集中于检测单个明确的目标物或一组目标物的存在。近年来,基于微阵列的诊断方法已经得到发展,这极大地促进了对可能存在于特定临床样本中的多种微生物的高通量平行检测。尽管已经描述了几种用于解释诊断微阵列的算法,但现有的方法都不能将来自阳性对照样本的训练数据纳入其中以提高性能。
为了专门解决这个问题,我们开发了一种新的解释算法 VIPR(使用概率算法进行病毒识别),它使用贝叶斯推理利用经验训练数据来优化检测灵敏度。为了说明这种方法,我们专注于使用定制的 HF 病毒微阵列检测引起出血热 (HF) 的病毒。VIPR 用于分析来自 33 种不同病毒的 110 个经验微阵列杂交。通过留一法交叉验证,达到了 94%的准确率。
VIPR 在这个数据集上优于之前描述的算法。VIPR 算法有可能广泛应用于临床诊断环境,其中阳性对照通常很容易获得用于生成训练数据。