Abstract
BackgroundAll 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.ResultsTo 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. ConclusionsVIPR 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.
Highlights
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
We developed a probabilistic algorithm for the purpose of analyzing diagnostic microarrays
To assess whether these viruses could be distinguished from close relatives that are not associated with hemorrhagic fever (HF), additional viruses were selected from the same families for testing
Summary
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. A microarray-based approach is effective for viral diagnosis of diseases that have a common phenotype, but may be caused by any of a number of different viruses. Microarrays focused on the diagnosis of respiratory disease [11,12,13,14] and encephalitis [3,4,5] have been described, as have much broader pan-viral microarrays [1,2,8]. A wide range of probe design strategies and microarray platforms can be used for diagnostic microarrays. While many diagnostic microarrays have been described, there are only three published algorithms, E-Predict [15], DetectiV [16] and PhyloDetect [17], with downloadable or webaccessible software that are available for analyzing data from diagnostic microarrays
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