Abstract
BackgroundRecent developments of high throughput sequencing technologies allow the characterization of the microbial communities inhabiting our world. Various metagenomic studies have suggested using microbial taxa as potential biomarkers for certain diseases. In practice, the number of available samples varies from experiment to experiment. Therefore, a robust biomarker detection algorithm is needed to provide a set of potential markers irrespective of the number of available samples. Consistent performance is essential to derive solid biological conclusions and to transfer these findings into clinical applications. Surprisingly, the consistency of a metagenomic biomarker detection algorithm with respect to the variation in the experiment size has not been addressed by the current state-of-art algorithms.ResultsWe propose a consistency-classification framework that enables the assessment of consistency and classification performance of a biomarker discovery algorithm. This evaluation protocol is based on random resampling to mimic the variation in the experiment size. Moreover, we model the metagenomic data matrix as a superposition of two matrices. The first matrix is a low-rank matrix that models the abundance levels of the irrelevant bacteria. The second matrix is a sparse matrix that captures the abundance levels of the bacteria that are differentially abundant between different phenotypes. Then, we propose a novel Robust Principal Component Analysis (RPCA) based biomarker discovery algorithm to recover the sparse matrix. RPCA belongs to the class of multivariate feature selection methods which treat the features collectively rather than individually. This provides the proposed algorithm with an inherent ability to handle the complex microbial interactions. Comprehensive comparisons of RPCA with the state-of-the-art algorithms on two realistic datasets are conducted. Results show that RPCA consistently outperforms the other algorithms in terms of classification accuracy and reproducibility performance.ConclusionsThe RPCA-based biomarker detection algorithm provides a high reproducibility performance irrespective of the complexity of the dataset or the number of selected biomarkers. Also, RPCA selects biomarkers with quite high discriminative accuracy. Thus, RPCA is a consistent and accurate tool for selecting taxanomical biomarkers for different microbial populations.ReviewersThis article was reviewed by Masanori Arita and Zoltan Gaspari.
Highlights
Recent developments of high throughput sequencing technologies allow the characterization of the microbial communities inhabiting our world
Data description Unless stated otherwise, the 16S rRNA gene sequencing reads were assigned to operational taxonomic units (OTUs) using the naive Bayesian classifier employed by the Ribosomal Database Project (RDP) [32]
The performance of our proposed scheme, Robust Principal Component Analysis (RPCA), is compared with the current state-ofthe-art algorithms proposed for identifying microbial biomarkers
Summary
Recent developments of high throughput sequencing technologies allow the characterization of the microbial communities inhabiting our world. Various metagenomic studies have suggested using microbial taxa as potential biomarkers for certain diseases. A robust biomarker detection algorithm is needed to provide a set of potential markers irrespective of the number of available samples. With trillions of microbes inhabiting the human body, bacteria play an essential role in defining the health and disease states of the host. These microbial inhabitants outnumber the human’s cells and comprise about 150 times more genes than the human genome [1]. Recent advancements in sequencing technologies have overcome these limitations and provided researchers with the taxonomic composition and functional capacity of microbial colonies [6, 7].
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