How chromosomes fold and how distal genomic elements interact with one another at a genomic scale have been actively pursued in the past decade following the seminal work describing the Chromosome Conformation Capture (3C) assay. Essentially, 3C-based technologies produce two-dimensional (2D) contact maps that capture interactions between genomic fragments. Accordingly, a plethora of analytical methods have been proposed to take a 2D contact map as input to recapitulate the underlying whole genome three-dimensional (3D) structure of the chromatin. However, their performance in terms of several factors, including data resolution and ability to handle contact map features, have not been sufficiently evaluated. This task is taken up in this article, in which we consider several recent and/or well-regarded methods, both optimization-based and model-based, for their aptness of producing 3D structures using contact maps generated based on a population of cells. These methods are evaluated and compared using both simulated and real data. Several criteria have been used. For simulated data sets, the focus is on accurate recapitulation of the entire structure given the existence of the gold standard. For real data sets, comparison with distances measured by Florescence in situ Hybridization and consistency with several genomic features of known biological functions are examined.

BACKGROUND: Assays that are capable of detecting genome-wide chromatin interactions have produced massive amount of data and led to great understanding of the chromosomal three-dimensional (3D) structure. As technology becomes more sophisticated, higher-and-higher resolution data are being produced, going from the initial 1 Megabases (Mb) resolution to the current 10 Kilobases (Kb) or even 1 Kb resolution. The availability of genome-wide interaction data necessitates development of analytical methods to recover the underlying 3D spatial chromatin structure, but challenges abound. Most of the methods were proposed for analyzing data at low resolution (1 Mb). Their behaviors are thus unknown for higher resolution data. For such data, one of the key features is the high proportion of "0" contact counts among all available data, in other words, the excess of zeros. RESULTS: To address the issue of excess of zeros, in this paper, we propose a truncated Random effect EXpression (tREX) method that can handle data at various resolutions. We then assess the performance of tREX and a number of leading existing methods for recovering the underlying chromatin 3D structure. This was accomplished by creating in-silico data to mimic multiple levels of resolution and submit the methods to a "stress test". Finally, we applied tREX and the comparison methods to a Hi-C dataset for which FISH measurements are available to evaluate estimation accuracy. CONCLUSION: The proposed tREX method achieves consistently good performance in all 30 simulated settings considered. It is not only robust to resolution level and underlying parameters, but also insensitive to model misspecification. This conclusion is based on observations made in terms of 3D structure estimation accuracy and preservation of topologically associated domains. Application of the methods to the human lymphoblastoid cell line data on chromosomes 14 and 22 further substantiates the superior performance of tREX: the constructed 3D structure from tREX is consistent with the FISH measurements, and the corresponding distances predicted by tREX have higher correlation with the FISH measurements than any of the comparison methods. SOFTWARE: An open-source R-package is available at http://www.stat.osu.edu/~statgen/Software/tRex.

Being able to predict the degree of visual discomfort that is felt when viewing stereoscopic 3D (S3D) images is an important goal toward ameliorating causative factors, such as excessive horizontal disparity, misalignments or mismatches between the left and right views of stereo pairs, or conflicts between different depth cues. Ideally, such a model should account for such factors as capture and viewing geometries, the distribution of disparities, and the responses of visual neurons. When viewing modern 3D displays, visual discomfort is caused primarily by changes in binocular vergence while accommodation in held fixed at the viewing distance to a flat 3D screen. This results in unnatural mismatches between ocular fixations and ocular focus that does not occur in normal direct 3D viewing. This accommodation vergence conflict can cause adverse effects, such as headaches, fatigue, eye strain, and reduced visual ability. Binocular vision is ultimately realized by means of neural mechanisms that subserve the sensorimotor control of eye movements. Realizing that the neuronal responses are directly implicated in both the control and experience of 3D perception, we have developed a model-based neuronal and statistical framework called the 3D visual discomfort predictor (3D-VDP)that automatically predicts the level of visual discomfort that is experienced when viewing S3D images. 3D-VDP extracts two types of features: 1) coarse features derived from the statistics of binocular disparities and 2) fine features derived by estimating the neural activity associated with the processing of horizontal disparities. In particular, we deploy a model of horizontal disparity processing in the extrastriate middle temporal region of occipital lobe. We compare the performance of 3D-VDP with other recent discomfort prediction algorithms with respect to correlation against recorded subjective visual discomfort scores,and show that 3D-VDP is statistically superior to the other methods.

Abstract Motivation : DNA methylation is an epigenetic change occurring in genomic CpG sequences that contribute to the regulation of gene transcription both in normal and malignant cells. Next-generation sequencing has been used to characterize DNA methylation status at the genome scale, but suffers from high sequencing cost in the case of whole-genome bisulfite sequencing, or from reduced resolution (inability to precisely define which of the CpGs are methylated) with capture-based techniques. Results : Here we present a computational method that computes nucleotide-resolution methylation values from capture-based data by incorporating fragment length profiles into a model of methylation analysis. We demonstrate that it compares favorably with nucleotide-resolution bisulfite sequencing and has better predictive power with respect to a reference than window-based methods, often used for enrichment data. The described method was used to produce the methylation data used in tandem with gene expression to produce a novel and clinically significant gene signature in acute myeloid leukemia. In addition, we introduce a complementary statistical method that uses this nucleotide-resolution methylation data for detection of differentially methylated features. Availability : Software in the form of Python and R scripts is available at http://bioserv.mps.ohio-state.edu/ premer and is free for non-commercial use. Contact : [email protected] ; [email protected] Supplementary information: Supplementary data are available at Bioinformatics online.

The tremendous explosion of image-, video-, and audio-enabled mobile devices, such as tablets and smart-phones in recent years, has led to an associated dramatic increase in the volume of captured and distributed multimedia content. In particular, the number of digital photographs being captured annually is approaching 100 billion in just the U.S. These pictures are increasingly being acquired by inexperienced, casual users under highly diverse conditions leading to a plethora of distortions, including blur induced by camera shake. In order to be able to automatically detect, correct, or cull images impaired by shake-induced blur, it is necessary to develop distortion models specific to and suitable for assessing the sharpness of camera-shaken images. Toward this goal, we have developed a no-reference framework for automatically predicting the perceptual quality of camera-shaken images based on their spectral statistics. Two kinds of features are defined that capture blur induced by camera shake. One is a directional feature, which measures the variation of the image spectrum across orientations. The second feature captures the shape, area, and orientation of the spectral contours of camera shaken images. We demonstrate the performance of an algorithm derived from these features on new and existing databases of images distorted by camera shake.

It is generally recognized that severe video distortions that are transient in space and/or time have a large effect on overall perceived video quality. In order to understand this phenomena, we study the distribution of spatio-temporally local quality scores obtained from several video quality assessment (VQA) algorithms on videos suffering from compression and lossy transmission over communication channels. We propose a content adaptive spatial and temporal pooling strategy based on the observed distribution. Our method adaptively emphasizes "worst" scores along both the spatial and temporal dimensions of a video sequence and also considers the perceptual effect of large-area cohesive motion flow such as egomotion. We demonstrate the efficacy of the method by testing it using three different VQA algorithms on the LIVE Video Quality database and the EPFL-PoliMI video quality database.

With the increasing popularity of video applications, the reliable measurement of perceived video quality has increased in importance. We study methods for pooling video quality scores over space and time. The method accounts for localized severe impairments of the signal which exhibit significant influence on the subjective impression of the overall signal quality. It also accounts for the effect of camera motion (egomotion) on perceived quality. The method arrived at is tested on the LIVE Video Quality Database and is shown to perform quite well.

We propose a novel visual scalable video coding (VSVC) framework, named VSVC H.264/AVC. In this approach, the non-uniform sampling characteristic of the human eye is used to modify scalable video coding (SVC) H.264/AVC. We exploit the visibility of video content and the scalability of the video codec to achieve optimal subjective visual quality given limited system resources. To achieve the largest coding gain with controlled perceptual quality degradation, a perceptual weighting scheme is deployed wherein the compressed video is weighted as a function of visual saliency and of the non-uniform distribution of retinal photoreceptors. We develop a resource allocation algorithm emphasizing both efficiency and fairness by controlling the size of the salient region in each quality layer. Efficiency is emphasized on the low quality layer of the SVC. The bits saved by eliminating perceptual redundancy in regions of low interest are allocated to lower block-level distortions in salient regions. Fairness is enforced on the higher quality layers by enlarging the size of the salient regions. The simulation results show that the proposed VSVC framework significantly improves the subjective visual quality of compressed videos.

Emerging multimedia applications have increased the need for video quality measurement. Motion is critical to this task, but is complicated owing to a variety of object movements and movement of the camera. Here, we categorize the various motion situations and deploy appropriate perceptual models to each category. We use these models to create a new approach to objective video quality assessment. Performance evaluation on the Laboratory for Image and Video Engineering (LIVE) Video Quality Database shows competitive performance compared to the leading contemporary VQA algorithms.

We describe a method for achieving perceptually minimal video distortion over packet-erasure networks using perceptually unequal loss protection (PULP). There are two main ingredients in the algorithm. First, a perceptual weighting scheme is employed wherein the compressed video is weighted as a function of the nonuniform distribution of retinal photoreceptors. Secondly, packets are assigned temporal importance within each group of pictures (GOP), recognizing that the severity of error propagation increases with elapsed time within a GOP. Using both frame-level perceptual importance and GOP-level hierarchical importance, the PULP algorithm seeks efficient forward error correction assignment that balances efficiency and fairness by controlling the size of identified salient region(s) relative to the channel state. PULP demonstrates robust performance and significantly improved subjective and objective visual quality in the face of burst packet losses.

A recent dynamic increase in demand for wireless multimedia services has greatly accelerated the research on cross layer optimization techniques for transmitting multimedia data over wireless channel. In this paper, we explore a novel theoretical approach for joint optimization between the rate distortion (RD) of H.264/AVC video and the link-capacity of MIMO parallel subchannels. We obtain the optimal power level of subchannels through an optimization problem to minimize total visual distortion. In the simulation results, compared to the water filling (WF) method, the proposed scheme provides better results in aspects of visual quality in the face of sum rate loss.

To achieve seamless multimedia streaming services over wireless networks, it is important to overcome inter-cell interference (ICI), particularly in cell border regions. In this regard scalable video coding (SVC) has been actively studied due to its advantage of channel adaptation. We explore an optimal solution for maximizing the expected visual entropy over an orthogonal frequency division multiplexing (OFDM)-based broadband network from the perspective of cross-layer optimization. An optimization problem is parameterized by a set of source and channel parameters that are acquired along the user location over a multicell environment. A suboptimal solution is suggested using a greedy algorithm that allocates the radio resources to the scalable bitstreams as a function of their visual importance. The simulation results show that the greedy algorithm effectively resists ICI in the cell border region, while conventional nonscalable coding suffers severely because of ICI.

For seamless multimedia streaming services, it is very important to overcome severe ICI (intercell interference) over wireless networks, particularly in the cell border region. SVC (scalable video coding) has been actively studied due to its advantage of channel adaptation. In this paper, we study an optimal solution for maximizing the expected visual entropy over an OFDM (orthogonal frequency division multiplexing)-based broadband network from the aspect of cross layer optimization. Based on this approach, an optimal set of source and channel parameters is obtained according to the user location over a multi-cell environment. From the numerical results, we quantify the optimal visual gain attained from the single layer video coding or the SVC according to channel capacity v.s. source data rate.