GPU--accelerated Computation for Statistical Analysis of the Next--Generation Sequencing Data

In this project we develop Graphics Processing Unit (GPU) based tools to address the statistical computation challenges in analyzing the next-generation sequencing data. Our work contains three components. First, we accelerate general statistical analysis in R. After studying various approaches of using GPU in R, we adopted the best solution to combine R with GPU. Second, we address a set of specific computation-intensive problems in simulating genetic variants in whole-genome sequencing data. Third, we break the CPU limitation of Variant Tools, a popular toolkit for the next-gen sequencing analysis, by extending its functionality to more the powerful parallel computation of GPU

Rapid Segmentation Techniques for Cardiac and Neuroimage Analysis

Recent technological advances in medical imaging have allowed for the quick acquisition of highly resolved data to aid in diagnosis and characterization of diseases or to guide interventions. In order to to be integrated into a clinical work flow, accurate and robust methods of analysis must be developed which manage this increase in data. Recent improvements in in- expensive commercially available graphics hardware and General-Purpose Programming on Graphics Processing Units (GPGPU) have allowed for many large scale data analysis problems to be addressed in meaningful time and will continue to as parallel computing technology improves. In this thesis we propose methods to tackle two clinically relevant image segmentation problems: a user-guided segmentation of myocardial scar from Late-Enhancement Magnetic Resonance Images (LE-MRI) and a multi-atlas segmentation pipeline to automatically segment and partition brain tissue from multi-channel MRI. Both methods are based on recent advances in computer vision, in particular max-flow optimization that aims at solving the segmentation problem in continuous space. This allows for (approximately) globally optimal solvers to be employed in multi-region segmentation problems, without the particular drawbacks of their discrete counterparts, graph cuts, which typically present with metrication artefacts. Max-flow solvers are generally able to produce robust results, but are known for being computationally expensive, especially with large datasets, such as volume images. Additionally, we propose two new deformable registration methods based on Gauss-Newton optimization and smooth the resulting deformation fields via total-variation regularization to guarantee the problem is mathematically well-posed. We compare the performance of these two methods against four highly ranked and well-known deformable registration methods on four publicly available databases and are able to demonstrate a highly accurate performance with low run times. The best performing variant is subsequently used in a multi-atlas segmentation pipeline for the segmentation of brain tissue and facilitates fast run times for this computationally expensive approach. All proposed methods are implemented using GPGPU for a substantial increase in computational performance and so facilitate deployment into clinical work flows. We evaluate all proposed algorithms in terms of run times, accuracy, repeatability and errors arising from user interactions and we demonstrate that these methods are able to outperform established methods. The presented approaches demonstrate high performance in comparison with established methods in terms of accuracy and repeatability while largely reducing run times due to the employment of GPU hardware

Flexible multivariate hemodynamics fMRI data analyses and simulations with PyHRF

International audienceAs part of fMRI data analysis, the pyhrf package provides a set of tools for addressing the two 3 main issues involved in intra-subject fMRI data analysis: (i) the localization of cerebral regions 4 that elicit evoked activity and (ii) the estimation of the activation dynamics also referenced to 5 as the recovery of the Hemodynamic Response Function (HRF). To tackle these two problems, 6 pyhrf implements the Joint Detection-Estimation framework (JDE) which recovers parcel-level 7 HRFs and embeds an adaptive spatio-temporal regularization scheme of activation maps. With 8 respect to the sole detection issue (i), the classical voxelwise GLM procedure is also available 9 through nipy, whereas Finite Impulse Response (FIR) and temporally regularized FIR models 10 are implemented to deal with HRF estimation concerns (ii). Several parcellation tools are also 11 integrated such as spatial and functional clustering. Parcellations may be used for spatial 12 averaging prior to FIR/RFIR analysis or to specify the spatial support of the HRF estimates 13 in the JDE approach. These analysis procedures can be applied either to volumic data sets or 14 to data projected onto the cortical surface. For validation purpose, this package is shipped with 15 artificial and real fMRI data sets, which are used in this paper to compare the outcome of the 16 different available approaches. The artificial fMRI data generator is also described to illustrate 17 how to simulate different activation configurations, HRF shapes or nuisance components. To 18 cope with the high computational needs for inference, pyhrf handles distributing computing 19 by exploiting cluster units as well as multiple cores computers. Finally, a dedicated viewer is 20 presented, which handles n-dimensional images and provides suitable features to explore whole 21 brain hemodynamics (time series, maps, ROI mask overlay)

Metric Gaussian variational inference

One main result of this dissertation is the development of Metric Gaussian Variational Inference (MGVI), a method to perform approximate inference in extremely high dimensions and for complex probabilistic models. The problem with high-dimensional and complex models is twofold. Fist, to capture the true posterior distribution accurately, a sufficiently rich approximation for it is required. Second, the number of parameters to express this richness scales dramatically with the number of model parameters. For example, explicitly expressing the correlation between all model parameters requires their squared number of correlation coefficients. In settings with millions of model parameter, this is unfeasible. MGVI overcomes this limitation by replacing the explicit covariance with an implicit approximation, which does not have to be stored and is accessed via samples. This procedure scales linearly with the problem size and allows to account for the full correlations in even extremely large problems. This makes it also applicable to significantly more complex setups. MGVI enabled a series of ambitious signal reconstructions by me and others, which will be showcased. This involves a time- and frequency-resolved reconstruction of the shadow around the black hole M87* using data provided by the Event Horizon Telescope Collaboration, a three-dimensional tomographic reconstruction of interstellar dust within 300pc around the sun from Gaia starlight-absorption and parallax data, novel medical imaging methods for computed tomography, an all-sky Faraday rotation map, combining distinct data sources, and simultaneous calibration and imaging with a radio-interferometer. The second main result is an an approach to use several, independently trained and deep neural networks to reason on complex tasks. Deep learning allows to capture abstract concepts by extracting them from large amounts of training data, which alleviates the necessity of an explicit mathematical formulation. Here a generative neural network is used as a prior distribution and certain properties are imposed via classification and regression networks. The inference is then performed in terms of the latent variables of the generator, which is done using MGVI and other methods. This allows to flexibly answer novel questions without having to re-train any neural network and to come up with novel answers through Bayesian reasoning. This novel approach of Bayesian reasoning with neural networks can also be combined with conventional measurement data

Cross layer reliability estimation for digital systems

Forthcoming manufacturing technologies hold the promise to increase multifuctional computing systems performance and functionality thanks to a remarkable growth of the device integration density. Despite the benefits introduced by this technology improvements, reliability is becoming a key challenge for the semiconductor industry. With transistor size reaching the atomic dimensions, vulnerability to unavoidable fluctuations in the manufacturing process and environmental stress rise dramatically. Failing to meet a reliability requirement may add excessive re-design cost to recover and may have severe consequences on the success of a product. %Worst-case design with large margins to guarantee reliable operation has been employed for long time. However, it is reaching a limit that makes it economically unsustainable due to its performance, area, and power cost. One of the open challenges for future technologies is building ``dependable'' systems on top of unreliable components, which will degrade and even fail during normal lifetime of the chip. Conventional design techniques are highly inefficient. They expend significant amount of energy to tolerate the device unpredictability by adding safety margins to a circuit's operating voltage, clock frequency or charge stored per bit. Unfortunately, the additional cost introduced to compensate unreliability are rapidly becoming unacceptable in today's environment where power consumption is often the limiting factor for integrated circuit performance, and energy efficiency is a top concern. Attention should be payed to tailor techniques to improve the reliability of a system on the basis of its requirements, ending up with cost-effective solutions favoring the success of the product on the market. Cross-layer reliability is one of the most promising approaches to achieve this goal. Cross-layer reliability techniques take into account the interactions between the layers composing a complex system (i.e., technology, hardware and software layers) to implement efficient cross-layer fault mitigation mechanisms. Fault tolerance mechanism are carefully implemented at different layers starting from the technology up to the software layer to carefully optimize the system by exploiting the inner capability of each layer to mask lower level faults. For this purpose, cross-layer reliability design techniques need to be complemented with cross-layer reliability evaluation tools, able to precisely assess the reliability level of a selected design early in the design cycle. Accurate and early reliability estimates would enable the exploration of the system design space and the optimization of multiple constraints such as performance, power consumption, cost and reliability. This Ph.D. thesis is devoted to the development of new methodologies and tools to evaluate and optimize the reliability of complex digital systems during the early design stages. More specifically, techniques addressing hardware accelerators (i.e., FPGAs and GPUs), microprocessors and full systems are discussed. All developed methodologies are presented in conjunction with their application to real-world use cases belonging to different computational domains

A Novel Approach of Dynamic Cross Correlation Analysis on Molecular Dynamics Simulations and Its Application to Ets1 Dimer–DNA Complex

The dynamic cross correlation (DCC) analysis is a popular method for analyzing the trajectories of molecular dynamics (MD) simulations. However, it is difficult to detect correlative motions that appear transiently in only a part of the trajectory, such as atomic contacts between the side-chains of amino acids, which may rapidly flip. In order to capture these multi-modal behaviors of atoms, which often play essential roles, particularly at the interfaces of macromolecules, we have developed the "multi-modal DCC (mDCC)" analysis. The mDCC is an extension of the DCC and it takes advantage of a Bayesian-based pattern recognition technique. We performed MD simulations for molecular systems modeled from the (Ets1)2-DNA complex and analyzed their results with the mDCC method. Ets1 is an essential transcription factor for a variety of physiological processes, such as immunity and cancer development. Although many structural and biochemical studies have so far been performed, its DNA binding properties are still not well characterized. In particular, it is not straightforward to understand the molecular mechanisms how the cooperative binding of two Ets1 molecules facilitates their recognition of Stromelysin-1 gene regulatory elements. A correlation network was constructed among the essential atomic contacts, and the two major pathways by which the two Ets1 molecules communicate were identified. One is a pathway via direct protein-protein interactions and the other is that via the bound DNA intervening two recognition helices. These two pathways intersected at the particular cytosine bases (C110/C11), interacting with the H1, H2, and H3 helices. Furthermore, the mDCC analysis showed that both pathways included the transient interactions at their intermolecular interfaces of Tyr396-C11 and Ala327-Asn380 in multi-modal motions of the amino acid side chains and the nucleotide backbone. Thus, the current mDCC approach is a powerful tool to reveal these complicated behaviors and scrutinize intermolecular communications in a molecular system

Estimating Local Function Complexity via Mixture of Gaussian Processes

Real world data often exhibit inhomogeneity, e.g., the noise level, the sampling distribution or the complexity of the target function may change over the input space. In this paper, we try to isolate local function complexity in a practical, robust way. This is achieved by first estimating the locally optimal kernel bandwidth as a functional relationship. Specifically, we propose Spatially Adaptive Bandwidth Estimation in Regression (SABER), which employs the mixture of experts consisting of multinomial kernel logistic regression as a gate and Gaussian process regression models as experts. Using the locally optimal kernel bandwidths, we deduce an estimate to the local function complexity by drawing parallels to the theory of locally linear smoothing. We demonstrate the usefulness of local function complexity for model interpretation and active learning in quantum chemistry experiments and fluid dynamics simulations.Comment: 19 pages, 16 figure

A discrete graph Laplacian for signal processing

In this thesis we exploit diffusion processes on graphs to effect two fundamental problems of image processing: denoising and segmentation. We treat these two low-level vision problems on the pixel-wise level under a unified framework: a graph embedding. Using this framework opens us up to the possibilities of exploiting recently introduced algorithms from the semi-supervised machine learning literature. We contribute two novel edge-preserving smoothing algorithms to the literature. Furthermore we apply these edge-preserving smoothing algorithms to some computational photography tasks. Many recent computational photography tasks require the decomposition of an image into a smooth base layer containing large scale intensity variations and a residual layer capturing fine details. Edge-preserving smoothing is the main computational mechanism in producing these multi-scale image representations. We, in effect, introduce a new approach to edge-preserving multi-scale image decompositions. Where as prior approaches such as the Bilateral filter and weighted-least squares methods require multiple parameters to tune the response of the filters our method only requires one. This parameter can be interpreted as a scale parameter. We demonstrate the utility of our approach by applying the method to computational photography tasks that utilise multi-scale image decompositions. With minimal modification to these edge-preserving smoothing algorithms we show that we can extend them to produce interactive image segmentation. As a result the operations of segmentation and denoising are conducted under a unified framework. Moreover we discuss how our method is related to region based active contours. We benchmark our proposed interactive segmentation algorithms against those based upon energy-minimisation, specifically graph-cut methods. We demonstrate that we achieve competitive performance

Review of Deep Learning Algorithms and Architectures

Deep learning (DL) is playing an increasingly important role in our lives. It has already made a huge impact in areas, such as cancer diagnosis, precision medicine, self-driving cars, predictive forecasting, and speech recognition. The painstakingly handcrafted feature extractors used in traditional learning, classification, and pattern recognition systems are not scalable for large-sized data sets. In many cases, depending on the problem complexity, DL can also overcome the limitations of earlier shallow networks that prevented efficient training and abstractions of hierarchical representations of multi-dimensional training data. Deep neural network (DNN) uses multiple (deep) layers of units with highly optimized algorithms and architectures. This paper reviews several optimization methods to improve the accuracy of the training and to reduce training time. We delve into the math behind training algorithms used in recent deep networks. We describe current shortcomings, enhancements, and implementations. The review also covers different types of deep architectures, such as deep convolution networks, deep residual networks, recurrent neural networks, reinforcement learning, variational autoencoders, and others.https://doi.org/10.1109/ACCESS.2019.291220

Contributions of Continuous Max-Flow Theory to Medical Image Processing

Discrete graph cuts and continuous max-flow theory have created a paradigm shift in many areas of medical image processing. As previous methods limited themselves to analytically solvable optimization problems or guaranteed only local optimizability to increasingly complex and non-convex functionals, current methods based now rely on describing an optimization problem in a series of general yet simple functionals with a global, but non-analytic, solution algorithms. This has been increasingly spurred on by the availability of these general-purpose algorithms in an open-source context. Thus, graph-cuts and max-flow have changed every aspect of medical image processing from reconstruction to enhancement to segmentation and registration. To wax philosophical, continuous max-flow theory in particular has the potential to bring a high degree of mathematical elegance to the field, bridging the conceptual gap between the discrete and continuous domains in which we describe different imaging problems, properties and processes. In Chapter 1, we use the notion of infinitely dense and infinitely densely connected graphs to transfer between the discrete and continuous domains, which has a certain sense of mathematical pedantry to it, but the resulting variational energy equations have a sense of elegance and charm. As any application of the principle of duality, the variational equations have an enigmatic side that can only be decoded with time and patience. The goal of this thesis is to show the contributions of max-flow theory through image enhancement and segmentation, increasing incorporation of topological considerations and increasing the role played by user knowledge and interactivity. These methods will be rigorously grounded in calculus of variations, guaranteeing fuzzy optimality and providing multiple solution approaches to addressing each individual problem