Computational Inference of Genome-Wide Protein-DNA Interactions Using High-Throughput Genomic Data

Transcriptional regulation has been studied intensively in recent decades. One important aspect of this regulation is the interaction between regulatory proteins, such as transcription factors (TF) and nucleosomes, and the genome. Different high-throughput techniques have been invented to map these interactions genome-wide, including ChIP-based methods (ChIP-chip, ChIP-seq, etc.), nuclease digestion methods (DNase-seq, MNase-seq, etc.), and others. However, a single experimental technique often only provides partial and noisy information about the whole picture of protein-DNA interactions. Therefore, the overarching goal of this dissertation is to provide computational developments for jointly modeling different experimental datasets to achieve a holistic inference on the protein-DNA interaction landscape.

We first present a computational framework that can incorporate the protein binding information in MNase-seq data into a thermodynamic model of protein-DNA interaction. We use a correlation-based objective function to model the MNase-seq data and a Markov chain Monte Carlo method to maximize the function. Our results show that the inferred protein-DNA interaction landscape is concordant with the MNase-seq data and provides a mechanistic explanation for the experimentally collected MNase-seq fragments. Our framework is flexible and can easily incorporate other data sources. To demonstrate this flexibility, we use prior distributions to integrate experimentally measured protein concentrations.

We also study the ability of DNase-seq data to position nucleosomes. Traditionally, DNase-seq has only been widely used to identify DNase hypersensitive sites, which tend to be open chromatin regulatory regions devoid of nucleosomes. We reveal for the first time that DNase-seq datasets also contain substantial information about nucleosome translational positioning, and that existing DNase-seq data can be used to infer nucleosome positions with high accuracy. We develop a Bayes-factor-based nucleosome scoring method to position nucleosomes using DNase-seq data. Our approach utilizes several effective strategies to extract nucleosome positioning signals from the noisy DNase-seq data, including jointly modeling data points across the nucleosome body and explicitly modeling the quadratic and oscillatory DNase I digestion pattern on nucleosomes. We show that our DNase-seq-based nucleosome map is highly consistent with previous high-resolution maps. We also show that the oscillatory DNase I digestion pattern is useful in revealing the nucleosome rotational context around TF binding sites.

Finally, we present a state-space model (SSM) for jointly modeling different kinds of genomic data to provide an accurate view of the protein-DNA interaction landscape. We also provide an efficient expectation-maximization algorithm to learn model parameters from data. We first show in simulation studies that the SSM can effectively recover underlying true protein binding configurations. We then apply the SSM to model real genomic data (both DNase-seq and MNase-seq data). Through incrementally increasing the types of genomic data in the SSM, we show that different data types can contribute complementary information for the inference of protein binding landscape and that the most accurate inference comes from modeling all available datasets.

This dissertation provides a foundation for future research by taking a step toward the genome-wide inference of protein-DNA interaction landscape through data integration.

Inversion of light scattering data by singular system analysis

We consider the problem of inverting experimental data obtained in light scattering experiments described by linear theories. We discuss applications to particle sizing and we describe fast and easy-to-implement algorithms which permit the extraction, from noisy measurements, of reliable information about the particle size distribution. © 1987, SPIE.

Analysis of classification accuracy for pre-filtered multichannel remote sensing data

Noise is one of the main factors degrading the quality of original multichannel remote sensing data and its presence influences classification efficiency, object detection, etc. Thus, pre-filtering is often used to remove noise and improve the solving of final tasks of multichannel remote sensing. Recent studies indicate that a classical model of additive noise is not adequate enough for images formed by modern multichannel sensors operating in visible and infrared bands. However, this fact is often ignored by researchers designing noise removal methods and algorithms. Because of this, we focus on the classification of multichannel remote sensing images in the case of signal-dependent noise present in component images. Three approaches to filtering of multichannel images for the considered noise model are analysed, all based on discrete cosine transform in blocks. The study is carried out not only in terms of conventional efficiency metrics used in filtering (MSE) but also in terms of multichannel data classification accuracy (probability of correct classification, confusion matrix). The proposed classification system combines the pre-processing stage where a DCT-based filter processes the blocks of the multichannel remote sensing image and the classification stage. Two modern classifiers are employed, radial basis function neural network and support vector machines. Simulations are carried out for three-channel image of Landsat TM sensor. Different cases of learning are considered: using noise-free samples of the test multichannel image, the noisy multichannel image and the pre-filtered one. It is shown that the use of the pre-filtered image for training produces better classification in comparison to the case of learning for the noisy image. It is demonstrated that the best results for both groups of quantitative criteria are provided if a proposed 3D discrete cosine transform filter equipped by variance stabilizing transform is applied. The classification results obtained for data pre-filtered in different ways are in agreement for both considered classifiers. Comparison of classifier performance is carried out as well. The radial basis neural network classifier is less sensitive to noise in original images, but after pre-filtering the performance of both classifiers is approximately the same.

Cost function adaptation: a stochastic gradient algorithm for data echo cancellation

A family of stochastic gradient algorithms and their behaviour in the data echo cancellation work platform are presented. The cost function adaptation algorithms use an error exponent update strategy based on an absolute error mapping, which is updated at every iteration. The quadratic and nonquadratic cost functions are special cases of the new family. Several possible realisations are introduced using these approaches. The noisy error problem is discussed and the digital recursive filter estimator is proposed. The simulation outcomes confirm the effectiveness of the proposed family of algorithms.

Web Data Extraction from Query Result Pages Based on Visual and Content Features

A rapidly increasing number of Web databases are now become accessible via
their HTML form-based query interfaces. Query result pages are dynamically generated
in response to user queries, which encode structured data and are displayed for human
use. Query result pages usually contain other types of information in addition to query
results, e.g., advertisements, navigation bar etc. The problem of extracting structured data
from query result pages is critical for web data integration applications, such as comparison
shopping, meta-search engines etc, and has been intensively studied. A number of approaches
have been proposed. As the structures of Web pages become more and more complex, the
existing approaches start to fail, and most of them do not remove irrelevant contents which
may a®ect the accuracy of data record extraction. We propose an automated approach for
Web data extraction. First, it makes use of visual features and query terms to identify data
sections and extracts data records in these sections. We also represent several content and
visual features of visual blocks in a data section, and use them to ¯lter out noisy blocks.
Second, it measures similarity between data items in di®erent data records based on their
visual and content features, and aligns them into di®erent groups so that the data in the
same group have the same semantics. The results of our experiments with a large set of
Web query result pages in di®erent domains show that our proposed approaches are highly
e®ective.

Integrating Multiple Point Statistics with Aerial Geophysical Data to assist Groundwater Flow Models

The process of accounting for heterogeneity has made significant advances in statistical research, primarily in the framework of stochastic analysis and the development of multiple-point statistics (MPS). Among MPS techniques, the direct sampling (DS) method is tested to determine its ability to delineate heterogeneity from aerial magnetics data in a regional sandstone aquifer intruded by low-permeability volcanic dykes in Northern Ireland, UK. The use of two two-dimensional bivariate training images aids in creating spatial probability distributions of heterogeneities of hydrogeological interest, despite relatively ‘noisy’ magnetics data (i.e. including hydrogeologically irrelevant urban noise and regional geologic effects). These distributions are incorporated into a hierarchy system where previously published density function and upscaling methods are applied to derive regional distributions of equivalent hydraulic conductivity tensor K. Several K models, as determined by several stochastic realisations of MPS dyke locations, are computed within groundwater flow models and evaluated by comparing modelled heads with field observations. Results show a significant improvement in model calibration when compared to a simplistic homogeneous and isotropic aquifer model that does not account for the dyke occurrence evidenced by airborne magnetic data. The best model is obtained when normal and reverse polarity dykes are computed separately within MPS simulations and when a probability threshold of 0.7 is applied. The presented stochastic approach also provides improvement when compared to a previously published deterministic anisotropic model based on the unprocessed (i.e. noisy) airborne magnetics. This demonstrates the potential of coupling MPS to airborne geophysical data for regional groundwater modelling.

Efficient estimation using the characteristic function : theory and applications with high frequency data

The attached file is created with Scientific Workplace Latex

Leveraging noisy side information for disentangling of factors of variation in a supervised setting

Ce mémoire est composé de trois articles et présente les résultats de travaux de recherche effectués dans le but d'améliorer les techniques actuelles permettant d'utiliser des données associées à certaines tâches dans le but d'aider à l'entraînement de réseaux de neurones sur une tâche différente. Les deux premiers articles présentent de nouveaux ensembles de données créés pour permettre une meilleure évaluation de ce type de techniques d'apprentissage machine. Le premier article introduit une suite d'ensembles de données pour la tâche de reconnaissance automatique de chiffres écrits à la main. Ces ensembles de données ont été générés à partir d'un ensemble de données déjà existant, MNIST, auquel des nouveaux facteurs de variation ont été ajoutés. Le deuxième article introduit un ensemble de données pour la tâche de reconnaissance automatique d'expressions faciales. Cet ensemble de données est composé d'images de visages qui ont été collectées automatiquement à partir du Web et ensuite étiquetées. Le troisième et dernier article présente deux nouvelles approches, dans le contexte de l'apprentissage multi-tâches, pour tirer avantage de données pour une tâche donnée afin d'améliorer les performances d'un modèle sur une tâche différente. La première approche est une généralisation des neurones Maxout récemment proposées alors que la deuxième consiste en l'application dans un contexte supervisé d'une technique permettant d'inciter des neurones à apprendre des fonctions orthogonales, à l'origine proposée pour utilisation dans un contexte semi-supervisé.

ECG Noise Removal using GA tuned Sign-Data Least Mean Square Algorithm

Adaptive filter is a primary method to filter Electrocardiogram (ECG), because it does not need the signal statistical characteristics. In this paper, an adaptive filtering technique for denoising the ECG based on Genetic Algorithm (GA) tuned Sign-Data Least Mean Square (SD-LMS) algorithm is proposed. This technique minimizes the mean-squared error between the primary input, which is a noisy ECG, and a reference input which can be either noise that is correlated in some way with the noise in the primary input or a signal that is correlated only with ECG in the primary input. Noise is used as the reference signal in this work. The algorithm was applied to the records from the MIT -BIH Arrhythmia database for removing the baseline wander and 60Hz power line interference. The proposed algorithm gave an average signal to noise ratio improvement of 10.75 dB for baseline wander and 24.26 dB for power line interference which is better than the previous reported works

Design and Development of Compact Chipless RFID Tags with High Data Encoding Capacity

The main objective of this thesis is to develop a compact chipless RFID tag with high data encoding capacity. The design and development of chipless RFID tag based on multiresonator and multiscatterer methods are presented first. An RFID tag using using SIR capable of 79bits is proposed. The thesis also deals with some of the properties of SIR like harmonic separation, independent control on resonant modes and the capability to change the electrical length. A chipless RFID reader working in a frequency band of 2.36GHz to 2.54GHz has been designed to show the feasibility of the RFID system. For a practical system, a new approach based on UWB Impulse Radar (UWB IR) technology is employed and the decoding methods from noisy backscattered signal are successfully demonstrated. The thesis also proposes a simple calibration procedure, which is able to decode the backscattered signal up to a distance of 80cm with 1mW output power.

Understanding the indoor environment through mining sensory data - A case study

A wireless sensor network (WSN) is a group of sensors linked by wireless medium to perform distributed sensing tasks. WSNs have attracted a wide interest from academia and industry alike due to their diversity of applications, including home automation, smart environment, and emergency services, in various buildings. The primary goal of a WSN is to collect data sensed by sensors. These data are characteristic of being heavily noisy, exhibiting temporal and spatial correlation. In order to extract useful information from such data, as this paper will demonstrate, people need to utilise various techniques to analyse the data. Data mining is a process in which a wide spectrum of data analysis methods is used. It is applied in the paper to analyse data collected from WSNs monitoring an indoor environment in a building. A case study is given to demonstrate how data mining can be used to optimise the use of the office space in a building.

Model estimation of cerebral hemodynamics between blood flow and volume changes: A data-based modeling approach

It is well known that there is a dynamic relationship between cerebral blood flow (CBF) and cerebral blood volume (CBV). With increasing applications of functional MRI, where the blood oxygen-level-dependent signals are recorded, the understanding and accurate modeling of the hemodynamic relationship between CBF and CBV becomes increasingly important. This study presents an empirical and data-based modeling framework for model identification from CBF and CBV experimental data. It is shown that the relationship between the changes in CBF and CBV can be described using a parsimonious autoregressive with exogenous input model structure. It is observed that neither the ordinary least-squares (LS) method nor the classical total least-squares (TLS) method can produce accurate estimates from the original noisy CBF and CBV data. A regularized total least-squares (RTLS) method is thus introduced and extended to solve such an error-in-the-variables problem. Quantitative results show that the RTLS method works very well on the noisy CBF and CBV data. Finally, a combination of RTLS with a filtering method can lead to a parsimonious but very effective model that can characterize the relationship between the changes in CBF and CBV.

Noisy kriging-based optimization methods: A unified implementation within the DiceOptim package

Kriging-based optimization relying on noisy evaluations of complex systems has recently motivated contributions from various research communities. Five strategies have been implemented in the DiceOptim package. The corresponding functions constitute a user-friendly tool for solving expensive noisy optimization problems in a sequential framework, while offering some flexibility for advanced users. Besides, the implementation is done in a unified environment, making this package a useful device for studying the relative performances of existing approaches depending on the experimental setup. An overview of the package structure and interface is provided, as well as a description of the strategies and some insight about the implementation challenges and the proposed solutions. The strategies are compared to some existing optimization packages on analytical test functions and show promising performances.

Seismic data from Colle Gnifetti glacie saddle around borehole KCI, Swiss Alps

Two seismic surveys were carried out on the high-altitude glacier saddle, Colle Gnifetti, Monte Rosa, Italy/Switzerland. Explosive and vibroseismic sources were tested to explore the best way to generate seismic waves to deduce shallow and intermediate properties (<100 m) of firn and ice. The explosive source (SISSY) excites strong surface and diving waves, degrading data quality for processing; no englacial reflections besides the noisy bed reflector are visible. However, the strong diving waves are analyzed to derive the density distribution of the firn pack, yielding results similar to a nearby ice core. The vibrator source (ElViS), used in both P- and SH-wave modes, produces detectable laterally coherent reflections within the firn and ice column. We compare these with ice-core and radar data. The SH-wave data are particularly useful in providing detailed, high-resolution information on firn and ice stratigraphy. Our analyses demonstrate the potential of seismic methods to determine physical properties of firn and ice, particularly density and potentially also crystal-orientation fabric.

Background foreground segmentation with RGB-D Kinect data: An efficient combination of classifiers

Low cost RGB-D cameras such as the Microsoft’s Kinect or the Asus’s Xtion Pro are completely changing the computer vision world, as they are being successfully used in several applications and research areas. Depth data are particularly attractive and suitable for applications based on moving objects detection through foreground/background segmentation approaches; the RGB-D applications proposed in literature employ, in general, state of the art foreground/background segmentation techniques based on the depth information without taking into account the color information. The novel approach that we propose is based on a combination of classifiers that allows improving background subtraction accuracy with respect to state of the art algorithms by jointly considering color and depth data. In particular, the combination of classifiers is based on a weighted average that allows to adaptively modifying the support of each classifier in the ensemble by considering foreground detections in the previous frames and the depth and color edges. In this way, it is possible to reduce false detections due to critical issues that can not be tackled by the individual classifiers such as: shadows and illumination changes, color and depth camouflage, moved background objects and noisy depth measurements. Moreover, we propose, for the best of the author’s knowledge, the first publicly available RGB-D benchmark dataset with hand-labeled ground truth of several challenging scenarios to test background/foreground segmentation algorithms.