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Next generation sequencing technology has led to the development of methods for the detection of novel sequence insertions (nsINS). Multiple signatures from short reads are usually extracted to improve nsINS detection performance. However, characterization of nsINSs larger than the mean insert size is still challenging. This article presents a new method, ERINS, to detect nsINS contents and genotypes of full spectrum range size. It integrates the features of structural variations and mapping states of split reads to find nsINS breakpoints, and then adopts a left-most mapping strategy to infer nsINS content by iteratively extending the standard reference at each breakpoint. Finally, it realigns all reads to the extended reference and infers nsINS genotypes through statistical testing on read counts. We test and validate the performance of ERINS on simulation and real sequencing datasets. The simulation experimental results demonstrate that it outperforms several peer methods with respect to sensitivity and precision. The real data application indicates that ERINS obtains high consistent results with those of previously reported and detects nsINSs over 200 base pairs that many other methods fail. In conclusion, ERINS can be used as a supplement to existing tools and will become a routine approach for characterizing nsINSs. [ABSTRACT FROM AUTHOR]

Characterizing copy number variations (CNVs) from sequenced genomes is a both feasible and cost-effective way to search for driver genes in cancer diagnosis. A number of existing algorithms for CNV detection only explored part of the features underlying sequence data and copy number structures, resulting in limited performance. Here, we describe CONDEL, a method for detecting CNVs from single tumor samples using high-throughput sequence data. CONDEL utilizes a novel statistic in combination with a peel-off scheme to assess the statistical significance of genome bins, and adopts a Bayesian approach to infer copy number gains, losses, and deletion zygosity based on statistical mixture models. We compare CONDEL to six peer methods on a large number of simulation datasets, showing improved performance in terms of true positive and false positive rates, and further validate CONDEL on three real datasets derived from the 1000 Genomes Project and the EGA archive. CONDEL obtained higher consistent results in comparison with other three single sample-based methods, and exclusively identified a number of CNVs that were previously associated with cancers. We conclude that CONDEL is a powerful tool for detecting copy number variations on single tumor samples even if these are sequenced at low-coverage. [ABSTRACT FROM AUTHOR]

Pulse-inversion subharmonic (PISH) imaging can display information relating to pure cavitation bubbles while excluding that of tissue. Although plane-wave-based ultrafast active cavitation imaging (UACI) can monitor the transient activities of cavitation bubbles, its resolution and cavitation-to-tissue ratio (CTR) are barely satisfactory but can be significantly improved by introducing eigenspace-based (ESB) adaptive beamforming. PISH and UACI are a natural combination for imaging of pure cavitation activity in tissue; however, it raises two problems: 1) the ESB beamforming is hard to implement in real time due to the enormous amount of computation associated with the covariance matrix inversion and eigendecomposition and 2) the narrowband characteristic of the subharmonic filter will incur a drastic degradation in resolution. Thus, in order to jointly address these two problems, we propose a new PISH–UACI method using novel fast ESB (F-ESB) beamforming and cavitation deconvolution for nonlinear signals. This method greatly reduces the computational complexity by using F-ESB beamforming through dimensionality reduction based on principal component analysis, while maintaining the high quality of ESB beamforming. The degraded resolution is recovered using cavitation deconvolution through a modified convolution model and compressive deconvolution. Both simulations and in vitro experiments were performed to verify the effectiveness of the proposed method. Compared with the ESB-based PISH–UACI, the entire computation of our proposed approach was reduced by 99%, while the axial resolution gain and CTR were increased by 3 times and 2 dB, respectively, confirming that satisfactory performance can be obtained for monitoring pure cavitation bubbles in tissue erosion. [ABSTRACT FROM PUBLISHER]

The axial resolution of ultrasonic imaging is confined by the temporal width of acoustic pulse generated by the transducer, which has a limited bandwidth. Deconvolution can eliminate this effect and, therefore, improve the resolution. However, most ultrasonic imaging methods perform deconvolution scan line by scan line, and therefore the information embedded within the neighbor scan lines is unexplored, especially for those materials with layered structures such as blood vessels. In this paper, a joint sparse representation model is proposed to increase the axial resolution of ultrasonic imaging. The proposed model combines the sparse deconvolution along the axial direction with a sparsity-favoring constraint along the lateral direction. Since the constraint explores the information embedded within neighbor scan lines by connecting nearby pixels in the ultrasound image, the axial resolution of the image improves after deconvolution. The results on simulated data showed that the proposed method can increase resolution and discover layered structure. Moreover, the results on real data showed that the proposed method can measure carotid intima-media thickness automatically with good quality ( $0.56\pm 0.03$ versus $0.60\pm 0.06$ mm manually). [ABSTRACT FROM PUBLISHER]

Sparse signal restoration is usually formulated as the minimization of a quadratic cost function \Vert \mbi y - \mbi A \mbi x \Vert2^{2} where \mbi A is a dictionary and \mbi x is an unknown sparse vector. It is well-known that imposing an \ell 0 constraint leads to an NP-hard minimization problem. The convex relaxation approach has received considerable attention, where the \ell 0-norm is replaced by the \ell 1-norm. Among the many effective \ell 1 solvers, the homotopy algorithm minimizes \Vert \mbi y - \mbi A \mbi x \Vert2^{2}+\lambda \Vert \mbi x \Vert 1 with respect to \mbi x for a continuum of \lambda ’s. It is inspired by the piecewise regularity of the \ell 1-regularization path, also referred to as the homotopy path. In this paper, we address the minimization problem \Vert \mbi y - \mbi A \mbi x \Vert2^{2}+\lambda \Vert \mbi x \Vert 0 for a continuum of \lambda ’s and propose two heuristic search algorithms for \ell 0-homotopy. Continuation Single Best Replacement is a forward–backward greedy strategy extending the Single Best Replacement algorithm, previously proposed for \ell 0-minimization at a given \lambda . The adaptive search of the \lambda -values is inspired by \ell 1-homotopy. \ell 0 Regularization Path Descent is a more complex algorithm exploiting the structural properties of the \ell 0-regularization path, which is piecewise constant with respect to \lambda . Both algorithms are empirically evaluated for difficult inverse problems involving ill-conditioned dictionaries. Finally, we show that they can be easily coupled with usual methods of model order selection. [ABSTRACT FROM PUBLISHER]

Common copy number variations (CNVs) refid="ref1"/ are small regions of genomic variations at the same loci across multiple samples, which can be detected with high resolution from next-generation sequencing (NGS) technique. Multiple sequencing data samples are often available from genomic studies; examples include sequences from multiple platforms and sequences from multiple individuals. By integrating complementary information from multiple data samples, detection power can be potentially improved. However, most of current CNV detection methods often process an individual sequence sample, or two samples in an abnormal versus matched normal study; researches on detecting common CNVs across multiple samples have been very limited but are much needed. In this paper, we propose a novel method to detect common CNVs from multiple sequencing samples by exploiting the concurrency of genomic variations in read depth signals derived from multiple NGS data. We use a penalized sparse regression model to fit multiple read depth profiles, based on which common CNV identification is formulated as a change-point detection problem. Finally, we validate the proposed method on both simulation and real data, showing that it can give both higher detection power and better break point estimation over several published CNV detection methods. [ABSTRACT FROM PUBLISHER]

Formulated as a least square problem under an \ell_0 constraint, sparse signal restoration is a discrete optimization problem, known to be NP complete. Classical algorithms include, by increasing cost and efficiency, matching pursuit (MP), orthogonal matching pursuit (OMP), orthogonal least squares (OLS), stepwise regression algorithms and the exhaustive search. We revisit the single most likely replacement (SMLR) algorithm, developed in the mid-1980s for Bernoulli–Gaussian signal restoration. We show that the formulation of sparse signal restoration as a limit case of Bernoulli–Gaussian signal restoration leads to an \ell_0-penalized least square minimization problem, to which SMLR can be straightforwardly adapted. The resulting algorithm, called single best replacement (SBR), can be interpreted as a forward–backward extension of OLS sharing similarities with stepwise regression algorithms. Some structural properties of SBR are put forward. A fast and stable implementation is proposed. The approach is illustrated on two inverse problems involving highly correlated dictionaries. We show that SBR is very competitive with popular sparse algorithms in terms of tradeoff between accuracy and computation time. [ABSTRACT FROM PUBLISHER]