Simulating variance heterogeneity in quantitative genome wide association studies.

BACKGROUND: Analyzing 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. RESULTS: A 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. CONCLUSIONS: We 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.

Robust Recurrent CNV Detection in the Presence of Inter-Subject Variability.

The study of recurrent copy number variations (CNVs) plays an important role in understanding the onset and evolution of complex diseases such as cancer. Array-based comparative genomic hybridization (aCGH) is a widely used microarray based technology for identifying CNVs. However, due to high noise levels and inter-sample variability, detecting recurrent CNVs from aCGH data remains a challenging topic. This paper proposes a novel method for identification of the recurrent CNVs. In the proposed method, the noisy aCGH data is modeled as the superposition of three matrices: a full-rank matrix of weighted piece-wise generating signals accounting for the clean aCGH data, a Gaussian noise matrix to model the inherent experimentation errors and other sources of error, and a sparse matrix to capture the sparse inter-sample (sample-specific) variations. We demonstrated the ability of our method to separate accurately recurrent CNVs from sample-specific variations and noise in both simulated (artificial) data and real data. The proposed method produced more accurate results than current state-of-the-art methods used in recurrent CNV detection and exhibited robustness to noise and sample-specific variations.

Understanding the Bioinformatics Challenges of Integrating Genomics into Healthcare.

Genomic data is paving the way towards personalized healthcare. By unveiling genetic disease-contributing factors, genomic data can aid in the detection, diagnosis, and treatment of a wide range of complex diseases. Integrating genomic data into healthcare is riddled with a wide range of challenges spanning social, ethical, legal, educational, economic, and technical aspects. Bioinformatics is a core integration aspect presenting an overwhelming number of unaddressed challenges. In this paper we tackle the fundamental bioinformatics integration concerns including: genomic data generation, storage, representation, and utilization in conjunction with clinical data. We divide the bioinformatics challenges into a series of seven intertwined integration aspects spanning the areas of informatics, knowledge management, and communication. For each aspect, we provide a detailed discussion of the current research directions, outstanding challenges, and possible resolutions. This paper seeks to help narrow the gap between the genomic applications, which are being predominantly utilized in research settings, and the clinical adoption of these applications.

A Survey of Software and Hardware Approaches to Performing Read Alignment in Next Generation Sequencing.

Computational genomics is an emerging field that is enabling us to reveal the origins of life and the genetic basis of diseases such as cancer. Next Generation Sequencing (NGS) technologies have unleashed a wealth of genomic information by producing immense amounts of raw data. Before any functional analysis can be applied to this data, read alignment is applied to find the genomic coordinates of the produced sequences. Alignment algorithms have evolved rapidly with the advancement in sequencing technology, striving to achieve biological accuracy at the expense of increasing space and time complexities. Hardware approaches have been proposed to accelerate the computational bottlenecks created by the alignment process. Although several hardware approaches have achieved remarkable speedups, most have overlooked important biological features, which have hampered their widespread adoption by the genomics community. In this paper, we provide a brief biological introduction to genomics and NGS. We discuss the most popular next generation read alignment tools and algorithms. Furthermore, we provide a comprehensive survey of the hardware implementations used to accelerate these algorithms.