DATA ANALYSIS WORKFLOW FOR GAS CHROMATOGRAPHY MASS SPECTROMETRY-BASED METABOLOMICS STUDIES

Metabolomics has emerged as an integral part of systems biology research that attempts to comprehensively study low molecular weight organic and inorganic metabolites under certain conditions within a biological system. Technological advances in the past decade have made it possible to carry out metabolomics studies in a high- throughput fashion using gas chromatography coupled with mass spectrometry. As a result, large volumes of data are produced from these studies and there is a pressing need for algorithms that can efficiently process and analyze the data in a high-throughput fashion as well. To address this need, we have developed computational algorithms and the associated software tool named an Automated Data Analysis Pipeline (ADAP). ADAP allows data to flow seamlessly through the data processing steps that include de- nosing, peak detection, deconvolution, alignment, compound identification and quantitation. The development of ADAP started in 2009 and the past four years have witnessed continuous improvements in its performance from ADAP-GC 1.0, to ADAP- GC 2.0, and to the current ADAP-GC 3.0. As part of the performance assessment of ADAP-GC, we have compared it with three other software tools. In this dissertation, I will present the computational details about these three versions of ADAP-GC, the capabilities of the software tool, and the results from software comparison

Selective attention and speech processing in the cortex

In noisy and complex environments, human listeners must segregate the mixture of sound sources arriving at their ears and selectively attend a single source, thereby solving a computationally difficult problem called the cocktail party problem. However, the neural mechanisms underlying these computations are still largely a mystery. Oscillatory synchronization of neuronal activity between cortical areas is thought to provide a crucial role in facilitating information transmission between spatially separated populations of neurons, enabling the formation of functional networks. In this thesis, we seek to analyze and model the functional neuronal networks underlying attention to speech stimuli and find that the Frontal Eye Fields play a central 'hub' role in the auditory spatial attention network in a cocktail party experiment. We use magnetoencephalography (MEG) to measure neural signals with high temporal precision, while sampling from the whole cortex. However, several methodological issues arise when undertaking functional connectivity analysis with MEG data. Specifically, volume conduction of electrical and magnetic fields in the brain complicates interpretation of results. We compare several approaches through simulations, and analyze the trade-offs among various measures of neural phase-locking in the presence of volume conduction. We use these insights to study functional networks in a cocktail party experiment. We then construct a linear dynamical system model of neural responses to ongoing speech. Using this model, we are able to correctly predict which of two speakers is being attended by a listener. We then apply this model to data from a task where people were attending to stories with synchronous and scrambled videos of the speakers' faces to explore how the presence of visual information modifies the underlying neuronal mechanisms of speech perception. This model allows us to probe neural processes as subjects listen to long stimuli, without the need for a trial-based experimental design. We model the neural activity with latent states, and model the neural noise spectrum and functional connectivity with multivariate autoregressive dynamics, along with impulse responses for external stimulus processing. We also develop a new regularized Expectation-Maximization (EM) algorithm to fit this model to electroencephalography (EEG) data

Tutorial: A guide to techniques for analysing recordings from the peripheral nervous system

The nervous system, through a combination of conscious and automatic processes, enables the regulation of the body and its interactions with the environment. The peripheral nervous system is an excellent target for technologies that seek to modulate, restore or enhance these abilities as it carries sensory and motor information that most directly relates to a target organ or function. However, many applications require a combination of both an effective peripheral nerve interface and effective signal processing techniques to provide selective and stable recordings. While there are many reviews on the design of peripheral nerve interfaces, reviews of data analysis techniques and translational considerations are limited. Thus, this tutorial aims to support new and existing researchers in the understanding of the general guiding principles, and introduces a taxonomy for electrode configurations, techniques and translational models to consider

Efficient coding of natural scenes improves neural system identification

Neural system identification aims at learning the response function of neurons to arbitrary stimuli using experimentally recorded data, but typically does not leverage normative principles such as efficient coding of natural environments. Visual systems, however, have evolved to efficiently process input from the natural environment. Here, we present a normative network regularization for system identification models by incorporating, as a regularizer, the efficient coding hypothesis, which states that neural response properties of sensory representations are strongly shaped by the need to preserve most of the stimulus information with limited resources. Using this approach, we explored if a system identification model can be improved by sharing its convolutional filters with those of an autoencoder which aims to efficiently encode natural stimuli. To this end, we built a hybrid model to predict the responses of retinal neurons to noise stimuli. This approach did not only yield a higher performance than the “stand-alone” system identification model, it also produced more biologically-plausible filters. We found these results to be consistent for retinal responses to different stimuli and across model architectures. Moreover, our normatively regularized model performed particularly well in predicting responses of direction-of-motion sensitive retinal neurons. In summary, our results support the hypothesis that efficiently encoding environmental inputs can improve system identification models of early visual processing

Recent Advances in Signal Processing

The signal processing task is a very critical issue in the majority of new technological inventions and challenges in a variety of applications in both science and engineering fields. Classical signal processing techniques have largely worked with mathematical models that are linear, local, stationary, and Gaussian. They have always favored closed-form tractability over real-world accuracy. These constraints were imposed by the lack of powerful computing tools. During the last few decades, signal processing theories, developments, and applications have matured rapidly and now include tools from many areas of mathematics, computer science, physics, and engineering. This book is targeted primarily toward both students and researchers who want to be exposed to a wide variety of signal processing techniques and algorithms. It includes 27 chapters that can be categorized into five different areas depending on the application at hand. These five categories are ordered to address image processing, speech processing, communication systems, time-series analysis, and educational packages respectively. The book has the advantage of providing a collection of applications that are completely independent and self-contained; thus, the interested reader can choose any chapter and skip to another without losing continuity

Change blindness: eradication of gestalt strategies

Arrays of eight, texture-defined rectangles were used as stimuli in a one-shot change blindness (CB) task where there was a 50% chance that one rectangle would change orientation between two successive presentations separated by an interval. CB was eliminated by cueing the target rectangle in the first stimulus, reduced by cueing in the interval and unaffected by cueing in the second presentation. This supports the idea that a representation was formed that persisted through the interval before being 'overwritten' by the second presentation (Landman et al, 2003 Vision Research 43149–164]. Another possibility is that participants used some kind of grouping or Gestalt strategy. To test this we changed the spatial position of the rectangles in the second presentation by shifting them along imaginary spokes (by ±1 degree) emanating from the central fixation point. There was no significant difference seen in performance between this and the standard task [F(1,4)=2.565, p=0.185]. This may suggest two things: (i) Gestalt grouping is not used as a strategy in these tasks, and (ii) it gives further weight to the argument that objects may be stored and retrieved from a pre-attentional store during this task

Medical image enhancement

Each image acquired from a medical imaging system is often part of a two-dimensional (2-D) image set whose total presents a three-dimensional (3-D) object for diagnosis. Unfortunately, sometimes these images are of poor quality. These distortions cause an inadequate object-of-interest presentation, which can result in inaccurate image analysis. Blurring is considered a serious problem. Therefore, “deblurring” an image to obtain better quality is an important issue in medical image processing. In our research, the image is initially decomposed. Contrast improvement is achieved by modifying the coefficients obtained from the decomposed image. Small coefficient values represent subtle details and are amplified to improve the visibility of the corresponding details. The stronger image density variations make a major contribution to the overall dynamic range, and have large coefficient values. These values can be reduced without much information loss

Autoencoding sensory substitution

Tens of millions of people live blind, and their number is ever increasing. Visual-to-auditory sensory substitution (SS) encompasses a family of cheap, generic solutions to assist the visually impaired by conveying visual information through sound. The required SS training is lengthy: months of effort is necessary to reach a practical level of adaptation. There are two reasons for the tedious training process: the elongated substituting audio signal, and the disregard for the compressive characteristics of the human hearing system. To overcome these obstacles, we developed a novel class of SS methods, by training deep recurrent autoencoders for image-to-sound conversion. We successfully trained deep learning models on different datasets to execute visual-to-auditory stimulus conversion. By constraining the visual space, we demonstrated the viability of shortened substituting audio signals, while proposing mechanisms, such as the integration of computational hearing models, to optimally convey visual features in the substituting stimulus as perceptually discernible auditory components. We tested our approach in two separate cases. In the first experiment, the author went blindfolded for 5 days, while performing SS training on hand posture discrimination. The second experiment assessed the accuracy of reaching movements towards objects on a table. In both test cases, above-chance-level accuracy was attained after a few hours of training. Our novel SS architecture broadens the horizon of rehabilitation methods engineered for the visually impaired. Further improvements on the proposed model shall yield hastened rehabilitation of the blind and a wider adaptation of SS devices as a consequence