Analysis-driven lossy compression of DNA microarray images

DNA microarrays are one of the fastest-growing new technologies in the field of genetic research, and DNA microarray images continue to grow in number and size. Since analysis techniques are under active and ongoing development, storage, transmission and sharing of DNA microarray images need be addressed, with compression playing a significant role. However, existing lossless coding algorithms yield only limited compression performance (compression ratios below 2:1), whereas lossy coding methods may introduce unacceptable distortions in the analysis process. This work introduces a novel Relative Quantizer (RQ), which employs non-uniform quantization intervals designed for improved compression while bounding the impact on the DNA microarray analysis. This quantizer constrains the maximum relative error introduced into quantized imagery, devoting higher precision to pixels critical to the analysis process. For suitable parameter choices, the resulting variations in the DNA microarray analysis are less than half of those inherent to the experimental variability. Experimental results reveal that appropriate analysis can still be performed for average compression ratios exceeding 4.5:1

Selection of Wavelet Basis Function for Image Compression : a Review

Wavelets are being suggested as a platform for various tasks in image processing. The advantage of wavelets lie in its time frequency resolution. The use of different basis functions in the form of different wavelets made the wavelet analysis as a destination for many applications. The performance of a particular technique depends on the wavelet coefficients arrived after applying the wavelet transform. The coefficients for a specific input signal depends on the basis functions used in the wavelet transform. Hence in this paper toward this end, different basis functions and their features are presented. As the image compression task depends on wavelet transform to large extent from few decades, the selection of basis function for image compression should be taken with care. In this paper, the factors influencing the performance of image compression are presented

Stochastic dynamics and wavelets techniques for system response analysis and diagnostics: Diverse applications in structural and biomedical engineering

In the first part of the dissertation, a novel stochastic averaging technique based on a Hilbert transform definition of the oscillator response displacement amplitude is developed. In comparison to standard stochastic averaging, the requirement of “a priori” determination of an equivalent natural frequency is bypassed, yielding flexibility in the ensuing analysis and potentially higher accuracy. Further, the herein proposed Hilbert transform based stochastic averaging is adapted for determining the time-dependent survival probability and first-passage time probability density function of stochastically excited nonlinear oscillators, even endowed with fractional derivative terms. To this aim, a Galerkin scheme is utilized to solve approximately the backward Kolmogorov partial differential equation governing the survival probability of the oscillator response. Next, the potential of the stochastic averaging technique to be used in conjunction with performance-based engineering design applications is demonstrated by proposing a stochastic version of the widely used incremental dynamic analysis (IDA). Specifically, modeling the excitation as a non-stationary stochastic process possessing an evolutionary power spectrum (EPS), an approximate closed-form expression is derived for the parameterized oscillator response amplitude probability density function (PDF). In this regard, IDA surfaces are determined providing the conditional PDF of the engineering demand parameter (EDP) for a given intensity measure (IM) value. In contrast to the computationally expensive Monte Carlo simulation, the methodology developed herein determines the IDA surfaces at minimal computational cost. In the second part of the dissertation, a novel multiple-input/single-output (MISO) system identification technique is developed for parameter identification of nonlinear and time-variant oscillators with fractional derivative terms subject to incomplete non-stationary data. The technique utilizes a representation of the nonlinear restoring forces as a set of parallel linear sub-systems. Next, a recently developed L1-norm minimization procedure based on compressive sensing theory is applied for determining the wavelet coefficients of the available incomplete non-stationary input-output (excitation-response) data. Several numerical examples are considered for assessing the reliability of the technique, even in the presence of incomplete and corrupted data. These include a 2-DOF time-variant Duffing oscillator endowed with fractional derivative terms, as well as a 2-DOF system subject to flow-induced forces where the non-stationary sea state possesses a recently proposed evolutionary version of the JONSWAP spectrum. In the third part of this dissertation, a joint time-frequency analysis technique based on generalized harmonic wavelets (GHWs) is developed for dynamic cerebral autoregulation (DCA) performance quantification. DCA is the continuous counter-regulation of the cerebral blood flow by the active response of cerebral blood vessels to the spontaneous or induced blood pressure fluctuations. Specifically, various metrics of the phase shift and magnitude of appropriately defined GHW-based transfer functions are determined based on data points over the joint time-frequency domain. The potential of these metrics to be used as a diagnostics tool for indicating healthy versus impaired DCA function is assessed by considering both healthy individuals and patients with unilateral carotid artery stenosis. Next, another application in biomedical engineering is pursued related to the Pulse Wave Imaging (PWI) technique. This relies on ultrasonic signals for capturing the propagation of pressure pulses along the carotid artery, and eventually for prognosis of focal vascular diseases (e.g., atherosclerosis and abdominal aortic aneurysm). However, to obtain a high spatio-temporal resolution the data are acquired at a high rate, in the order of kilohertz, yielding large datasets. To address this challenge, an efficient data compression technique is developed based on the multiresolution wavelet decomposition scheme, which exploits the high correlation of adjacent RF-frames generated by the PWI technique. Further, a sparse matrix decomposition is proposed as an efficient way to identify the boundaries of the arterial wall in the PWI technique

Analysis-driven lossy compression of DNA microarray images

DNA microarrays are one of the fastest-growing new technologies in the field of genetic research, and DNA microarray images continue to grow in number and size. Since analysis techniques are under active and ongoing development, storage, transmission and sharing of DNA microarray images need be addressed, with compression playing a significant role. However, existing lossless coding algorithms yield only limited compression performance (compression ratios below 2:1), whereas lossy coding methods may introduce unacceptable distortions in the analysis process. This work introduces a novel Relative Quantizer (RQ), which employs non-uniform quantization intervals designed for improved compression while bounding the impact on the DNA microarray analysis. This quantizer constrains the maximum relative error introduced into quantized imagery, devoting higher precision to pixels critical to the analysis process. For suitable parameter choices, the resulting variations in the DNA microarray analysis are less than half of those inherent to the experimental variability. Experimental results reveal that appropriate analysis can still be performed for average compression ratios exceeding 4.5:1

The stratification potential of a novel epigenetic biomarker in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease of the joints, that affects 0.5-1% of the population globally. While primarily affecting the joints, systemic inflammation impacts other organs and the disease has a significant socioeconomic burden. While there are a wide range of medications to pharmacologically manage RA, it is a largely heterogeneous disease and the current treatment strategy does not consider the heterogeneity between patients. As such, precision medicine approaches to treatment are desired. A 5-loop chromosome conformation signature (CCS) was identified that had 90% specificity at predicting non-response to methotrexate (MTX) in early RA. These epigenetic biomarkers offer a novel strategy for improving patient care, and provide insight into disease pathogenesis. The aim of the work presented in this thesis was to further characterise this novel epigenetic biomarker. Investigation of this biomarker also offered the opportunity to hypothesise about underlying pathogenesis. A combination of molecular analysis of patient samples, and in-silico methodologies were applied to investigate these aims. In the first instance, the CCS was validated as a biomarker for identifying MTX responders using bioinformatic tools. Preliminary work was also carried out to identify the optimal method for detecting chromosome loops from the signature in the lab. Quantitative PCR was thoroughly explored, but excluded as a reliable and robust method of loop detection for our signature of interest. It was also found that the CCS was MTX specific, and alternative signatures would be required for prediction of response to other csDMARDs. Further validation of the signature, using an independent clinical cohort, revealed that specific loops from the CCS held stratification potential while others did not. In-silico investigations revealed different epigenetic landscapes exist between loops associated with responders and non-responders to MTX. Specifically, data suggests loops associated with responders exist in an environment which enhances gene transcription, while loops associated with non-responders have an environment indicating potential for gene repression. Differences in chromatin architecture, revealed through a discovery microarray, have indicated that 3D epigenetic endotypes exist within the early RA population. Further investigations suggested each endotype have different, unique pathways that are highly regulated. Furthermore, results revealed that there is a stable RA chromatin signature that exists, which highlights the importance of the 3D epigenome underpinning disease. In summation, this body of work has shown CCS to be promising biomarker for the stratification of the early RA population. Furthermore, thorough investigation of this signature highlighted novel pathways that may be involved in disease pathogenesis. This work has exciting potential to contribute to improved RA treatment in the future