Mustafa Alshawaqfeh

Inferring microbial interaction networks from metagenomic data using SgLV-EKF algorithm

BackgroundInferring the microbial interaction networks (MINs) and modeling their dynamics are critical in understanding the mechanisms of the bacterial ecosystem and designing antibiotic and/or probiotic therapies. Recently, several approaches were proposed to infer MINs using the generalized Lotka-Volterra (gLV) model. Main drawbacks of these models include the fact that these models only consider the measurement noise without taking into consideration the uncertainties in the underlying dynamics. Furthermore, inferring the MIN is characterized by the limited number of observations and nonlinearity in the regulatory mechanisms. Therefore, novel estimation techniques are needed to address these challenges.ResultsThis work proposes SgLV-EKF: a stochastic gLV model that adopts the extended Kalman filter (EKF) algorithm to model the MIN dynamics. In particular, SgLV-EKF employs a stochastic modeling of the MIN by adding a noise term to the dynamical model to compensate for modeling uncertainties. This stochastic modeling is more realistic than the conventional gLV model which assumes that the MIN dynamics are perfectly governed by the gLV equations. After specifying the stochastic model structure, we propose the EKF to estimate the MIN. SgLV-EKF was compared with two similarity-based algorithms, one algorithm from the integral-based family and two regression-based algorithms, in terms of the achieved performance on two synthetic data-sets and two real data-sets. The first data-set models the randomness in measurement data, whereas, the second data-set incorporates uncertainties in the underlying dynamics. The real data-sets are provided by a recent study pertaining to an antibiotic-mediated Clostridium difficile infection. The experimental results demonstrate that SgLV-EKF outperforms the alternative methods in terms of robustness to measurement noise, modeling errors, and tracking the dynamics of the MIN.ConclusionsPerformance analysis demonstrates that the proposed SgLV-EKF algorithm represents a powerful and reliable tool to infer MINs and track their dynamics.

An Overview of NCA-Based Algorithms for Transcriptional Regulatory Network Inference

In systems biology, the regulation of gene expressions involves a complex network of regulators. Transcription factors (TFs) represent an important component of this network: they are proteins that control which genes are turned on or off in the genome by binding to specific DNA sequences. Transcription regulatory networks (TRNs) describe gene expressions as a function of regulatory inputs specified by interactions between proteins and DNA. A complete understanding of TRNs helps to predict a variety of biological processes and to diagnose, characterize and eventually develop more efficient therapies. Recent advances in biological high-throughput technologies, such as DNA microarray data and next-generation sequence (NGS) data, have made the inference of transcription factor activities (TFAs) and TF-gene regulations possible. Network component analysis (NCA) represents an efficient computational framework for TRN inference from the information provided by microarrays, ChIP-on-chip and the prior information about TF-gene regulation. However, NCA suffers from several shortcomings. Recently, several algorithms based on the NCA framework have been proposed to overcome these shortcomings. This paper first overviews the computational principles behind NCA, and then, it surveys the state-of-the-art NCA-based algorithms proposed in the literature for TRN reconstruction.

Consistent metagenomic biomarker detection via robust PCA

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.

Simulating variance heterogeneity in quantitative genome wide association studies

BackgroundAnalyzing Variance heterogeneity in genome wide association studies (vGWAS) is an emerging approach for detecting genetic loci involved in gene-gene and gene-environment interactions. vGWAS analysis detects variability in phenotype values across genotypes, as opposed to typical GWAS analysis, which detects variations in the mean phenotype value.ResultsA handful of vGWAS analysis methods have been recently introduced in the literature. However, very little work has been done for evaluating these methods. To enable the development of better vGWAS analysis methods, this work presents the first quantitative vGWAS simulation procedure. To that end, we describe the mathematical framework and algorithm for generating quantitative vGWAS phenotype data from genotype profiles. Our simulation model accounts for both haploid and diploid genotypes under different modes of dominance. Our model is also able to simulate any number of genetic loci causing mean and variance heterogeneity.ConclusionsWe demonstrate the utility of our simulation procedure through generating a variety of genetic loci types to evaluate common GWAS and vGWAS analysis methods. The results of this evaluation highlight the challenges current tools face in detecting GWAS and vGWAS loci.

A Survey of Machine Learning Algorithms and Their Applications in Cognitive Radio

Cognitive radio (CR) technology is a promising candidate for next generation intelligent wireless networks. The cognitive engine plays the role of the brain for the CR and the learning engine is its core. In order to fully exploit the features of CRs, the learning engine should be improved. Therefore, in this study, we discuss several machine learning algorithms and their applications for CRs in terms of spectrum sensing, modulation classification and power allocation.

Simulating Variance Heterogeneity in Quantitative Genome Wide Association Studies

Variance heterogeneity in genome wide association studies (vGWAS) is a recent approach that is gaining interest due to its ability to detect non-additive interactions in the genome. Recent studies have found that in the presence of a non-additive interaction, such as a gene-gene or a gene-environment interaction, variance heterogeneity is introduced in at least one of the interacting loci. As opposed to typical GWAS analysis techniques, vGWAS tests the variance at each targeted location to identify the genotypes that cause a significant differentiation in the variance. The development of vGWAS methods to perform this task is an ongoing process in this relatively new field. In order to contribute to this process, in this work we introduce a mathematical framework and algorithm for simulating quantitative vGWAS data. An accurate simulation process is essential for the development and evaluation of vGWAS methods through establishing a ground truth for comparison. The presented simulation model accounts for both haploid and diploid genotypes under different modes of dominance. We used this simulation process to assess the performance of existing quantitative vGWAS detection algorithms. Finally, we use this assessment to point out the challenges these methods face, in hope of motivating the development of more advanced methods.

Sparse-low rank matrix decomposition framework for identifying potential biomarkers for inflammatory bowel disease

Inflammatory bowel disease (IBD) is a class of uncured chronic diseases which causes severe discomfort and in some cases could lead to life-threatening complications. Recent studies suggest a relationship between IBD and the gut microbiota. These findings reveal potential for identifying bacterial biomarkers for IBD to enable the detection and further investigation into unknown aspects of the disease. This work presents a novel method for identifying microbial biomarkers using robust principal component analysis (RPCA). Our method uses matrix decomposition to separate bacteria exhibiting a difference in abundance between healthy and diseased samples from the bacteria that have not undergone substantial change in abundance. Our method then ranks and identifies the top bacteria to be used as biomarkers. We contrast the proposed method with three well used state-of-the-art bacterial biomarker detection approaches over two datasets in relation to IBD. Our method outperforms the competing methods on the different evaluation cases.

Reliable Biomarker discovery from Metagenomic data via RegLRSD algorithm

BackgroundBiomarker detection presents itself as a major means of translating biological data into clinical applications. Due to the recent advances in high throughput sequencing technologies, an increased number of metagenomics studies have suggested the dysbiosis in microbial communities as potential biomarker for certain diseases. The reproducibility of the results drawn from metagenomic data is crucial for clinical applications and to prevent incorrect biological conclusions. The variability in the sample size and the subjects participating in the experiments induce diversity, which may drastically change the outcome of biomarker detection algorithms. Therefore, a robust biomarker detection algorithm that ensures the consistency of the results irrespective of the natural diversity present in the samples is needed.ResultsToward this end, this paper proposes a novel Regularized Low Rank-Sparse Decomposition (RegLRSD) algorithm. RegLRSD models the bacterial abundance data as a superposition between a sparse matrix and a low-rank matrix, which account for the differentially and non-differentially abundant microbes, respectively. Hence, the biomarker detection problem is cast as a matrix decomposition problem. In order to yield more consistent and solid biological conclusions, RegLRSD incorporates the prior knowledge that the irrelevant microbes do not exhibit significant variation between samples belonging to different phenotypes. Moreover, an efficient algorithm to extract the sparse matrix is proposed. Comprehensive comparisons of RegLRSD with the state-of-the-art algorithms on three realistic datasets are presented. The obtained results demonstrate that RegLRSD consistently outperforms the other algorithms in terms of reproducibility performance and provides a marker list with high classification accuracy.ConclusionsThe proposed RegLRSD algorithm for biomarker detection provides high reproducibility and classification accuracy performance regardless of the dataset complexity and the number of selected biomarkers. This renders RegLRSD as a reliable and powerful tool for identifying potential metagenomic biomarkers.