On Provable Algorithms for Determination of Continuous Protein Interdomain Motions from Residual Dipolar Couplings

Dynamics of biomolecules over various spatial and time scales are essential for biological functions such as molecular recognition, catalysis and signaling. However, reconstruction of biomolecular dynamics from experimental observables requires the determination of a conformational probability distribution. Unfortunately, these distributions cannot be fully constrained by the limited information from experiments, making the problem an ill-posed one in the terminology of Hadamard. The ill-posed nature of the problem comes from the fact that it has no unique solution. Multiple or even an infinite number of solutions may exist. To avoid the ill-posed nature, the problem needs to be regularized by making assumptions, which inevitably introduce biases into the result.

Here, I present two continuous probability density function approaches to solve an important inverse problem called the RDC trigonometric moment problem. By focusing on interdomain orientations we reduced the problem to determination of a distribution on the 3D rotational space from residual dipolar couplings (RDCs). We derived an analytical equation that relates alignment tensors of adjacent domains, which serves as the foundation of the two methods. In the first approach, the ill-posed nature of the problem was avoided by introducing a continuous distribution model, which enjoys a smoothness assumption. To find the optimal solution for the distribution, we also designed an efficient branch-and-bound algorithm that exploits the mathematical structure of the analytical solutions. The algorithm is guaranteed to find the distribution that best satisfies the analytical relationship. We observed good performance of the method when tested under various levels of experimental noise and when applied to two protein systems. The second approach avoids the use of any model by employing maximum entropy principles. This 'model-free' approach delivers the least biased result which presents our state of knowledge. In this approach, the solution is an exponential function of Lagrange multipliers. To determine the multipliers, a convex objective function is constructed. Consequently, the maximum entropy solution can be found easily by gradient descent methods. Both algorithms can be applied to biomolecular RDC data in general, including data from RNA and DNA molecules.

Algorithms for Geometric Matching, Clustering, and Covering

With the popularization of GPS-enabled devices such as mobile phones, location data are becoming available at an unprecedented scale. The locations may be collected from many different sources such as vehicles moving around a city, user check-ins in social networks, and geo-tagged micro-blogging photos or messages. Besides the longitude and latitude, each location record may also have a timestamp and additional information such as the name of the location. Time-ordered sequences of these locations form trajectories, which together contain useful high-level information about people's movement patterns.

The first part of this thesis focuses on a few geometric problems motivated by the matching and clustering of trajectories. We first give a new algorithm for computing a matching between a pair of curves under existing models such as dynamic time warping (DTW). The algorithm is more efficient than standard dynamic programming algorithms both theoretically and practically. We then propose a new matching model for trajectories that avoids the drawbacks of existing models. For trajectory clustering, we present an algorithm that computes clusters of subtrajectories, which correspond to common movement patterns. We also consider trajectories of check-ins, and propose a statistical generative model, which identifies check-in clusters as well as the transition patterns between the clusters.

The second part of the thesis considers the problem of covering shortest paths in a road network, motivated by an EV charging station placement problem. More specifically, a subset of vertices in the road network are selected to place charging stations so that every shortest path contains enough charging stations and can be traveled by an EV without draining the battery. We first introduce a general technique for the geometric set cover problem. This technique leads to near-linear-time approximation algorithms, which are the state-of-the-art algorithms for this problem in either running time or approximation ratio. We then use this technique to develop a near-linear-time algorithm for this

shortest-path cover problem.

Evaluating the spatial transferability and temporal repeatability of remote-sensing-based lake water quality retrieval algorithms at the European scale: a meta-analysis approach

Many studies have shown the considerable potential for the application of remote-sensing-based methods for deriving estimates of lake water quality. However, the reliable application of these methods across time and space is complicated by the diversity of lake types, sensor configuration, and the multitude of different algorithms proposed. This study tested one operational and 46 empirical algorithms sourced from the peer-reviewed literature that have individually shown potential for estimating lake water quality properties in the form of chlorophyll-a (algal biomass) and Secchi disc depth (SDD) (water transparency) in independent studies. Nearly half (19) of the algorithms were unsuitable for use with the remote-sensing data available for this study. The remaining 28 were assessed using the Terra/Aqua satellite archive to identify the best performing algorithms in terms of accuracy and transferability within the period 2001–2004 in four test lakes, namely Vänern, Vättern, Geneva, and Balaton. These lakes represent the broad continuum of large European lake types, varying in terms of eco-region (latitude/longitude and altitude), morphology, mixing regime, and trophic status. All algorithms were tested for each lake separately and combined to assess the degree of their applicability in ecologically different sites. None of the algorithms assessed in this study exhibited promise when all four lakes were combined into a single data set and most algorithms performed poorly even for specific lake types. A chlorophyll-a retrieval algorithm originally developed for eutrophic lakes showed the most promising results (R2 = 0.59) in oligotrophic lakes. Two SDD retrieval algorithms, one originally developed for turbid lakes and the other for lakes with various characteristics, exhibited promising results in relatively less turbid lakes (R2 = 0.62 and 0.76, respectively). The results presented here highlight the complexity associated with remotely sensed lake water quality estimates and the high degree of uncertainty due to various limitations, including the lake water optical properties and the choice of methods.

Distributed parallelization of greedy Mobile Network Optimization algorithms

The Mobile Network Optimization (MNO) technologies have advanced at a tremendous pace in recent years. And the Dynamic Network Optimization (DNO) concept emerged years ago, aimed to continuously optimize the network in response to variations in network traffic and conditions. Yet, DNO development is still at its infancy, mainly hindered by a significant bottleneck of the lengthy optimization runtime. This paper identifies parallelism in greedy MNO algorithms and presents an advanced distributed parallel solution. The solution is designed, implemented and applied to real-life projects whose results yield a significant, highly scalable and nearly linear speedup up to 6.9 and 14.5 on distributed 8-core and 16-core systems respectively. Meanwhile, optimization outputs exhibit self-consistency and high precision compared to their sequential counterpart. This is a milestone in realizing the DNO. Further, the techniques may be applied to similar greedy optimization algorithm based applications.

Asynchronous distributed parallelization of mobile network optimization algorithms

It has been years since the introduction of the Dynamic Network Optimization (DNO) concept, yet the DNO development is still at its infant stage, largely due to a lack of breakthrough in minimizing the lengthy optimization runtime. Our previous work, a distributed parallel solution, has achieved a significant speed gain. To cater for the increased optimization complexity pressed by the uptake of smartphones and tablets, however, this paper examines the potential areas for further improvement and presents a novel asynchronous distributed parallel design that minimizes the inter-process communications. The new approach is implemented and applied to real-life projects whose results demonstrate an augmented acceleration of 7.5 times on a 16-core distributed system compared to 6.1 of our previous solution. Moreover, there is no degradation in the optimization outcome. This is a solid sprint towards the realization of DNO.

Joint Analysis of Multiple Algorithms and Performance Measures

There has been an increasing interest in the development of new methods using Pareto optimality to deal with multi-objective criteria (for example, accuracy and time complexity). Once one has developed an approach to a problem of interest, the problem is then how to compare it with the state of art. In machine learning, algorithms are typically evaluated by comparing their performance on different data sets by means of statistical tests. Standard tests used for this purpose are able to consider jointly neither performance measures nor multiple competitors at once. The aim of this paper is to resolve these issues by developing statistical procedures that are able to account for multiple competing measures at the same time and to compare multiple algorithms altogether. In particular, we develop two tests: a frequentist procedure based on the generalized likelihood-ratio test and a Bayesian procedure based on a multinomial-Dirichlet conjugate model. We further extend them by discovering conditional independences among measures to reduce the number of parameters of such models, as usually the number of studied cases is very reduced in such comparisons. Data from a comparison among general purpose classifiers is used to show a practical application of our tests.

Comparison of module detection algorithms in protein networks and investigation of the biological meaning of predicted modules

Background
It is generally acknowledged that a functional understanding of a biological system can only be obtained by an understanding of the collective of molecular interactions in form of biological networks. Protein networks are one particular network type of special importance, because proteins form the functional base units of every biological cell. On a mesoscopic level of protein networks, modules are of significant importance because these building blocks may be the next elementary functional level above individual proteins allowing to gain insight into fundamental organizational principles of biological cells.
Results
In this paper, we provide a comparative analysis of five popular and four novel module detection algorithms. We study these module prediction methods for simulated benchmark networks as well as 10 biological protein interaction networks (PINs). A particular focus of our analysis is placed on the biological meaning of the predicted modules by utilizing the Gene Ontology (GO) database as gold standard for the definition of biological processes. Furthermore, we investigate the robustness of the results by perturbing the PINs simulating in this way our incomplete knowledge of protein networks.
Conclusions
Overall, our study reveals that there is a large heterogeneity among the different module prediction algorithms if one zooms-in the biological level of biological processes in the form of GO terms and all methods are severely affected by a slight perturbation of the networks. However, we also find pathways that are enriched in multiple modules, which could provide important information about the hierarchical organization of the system

Congenital nasolacrimal duct obstruction:Comparison of two different treatment algorithms

Purpose: To clarify the most appropriate treatment regimen for congenital nasolacrimal duct obstruction (CNLDO). Methods: A retrospective observational analysis was performed of patients undergoing probing with or without intubation to treat CNLDO in a single institution (Royal Victoria Hospital, Belfast) from 2006 to 2011. Results: Based on exclusion criteria, 246 eyes of 177 patients (aged 0 to 9.8 years with a mean age of 2.1 years) were included in this study: 187 (76%) eyes had successful outcome at first intervention with primary probing, whereas 56 (23%) eyes underwent secondary intervention. There were no significant differences by gender, age, or obstruction complexity between the successful and unsuccessful patients with first intervention. For those patients requiring secondary intervention, 16 of 24 (67%) eyes had successful probing, whereas 22 of 24 (92%) had successful intubation. Patients with intubation as a secondary procedure were significantly more likely to have a successful outcome (P = .037). Statistical analysis was performed using the Fisher's exact test and Barnard's exact test. Conclusions: Primary probing for CNLDO has a high success rate that is not adversely affected by increasing age. This study also indicates that if initial probing is unsuccessful, nasolacrimal intubation rather than repeat probing yields a significantly higher success rate.

Data Mining for Network Intrusion Detection : A comparison of data mining algorithms and an analysis of relevant features for detecting cyber-attacks

Data mining can be defined as the extraction of implicit, previously un-known, and potentially useful information from data. Numerous re-searchers have been developing security technology and exploring new methods to detect cyber-attacks with the DARPA 1998 dataset for Intrusion Detection and the modified versions of this dataset KDDCup99 and NSL-KDD, but until now no one have examined the performance of the Top 10 data mining algorithms selected by experts in data mining. The compared classification learning algorithms in this thesis are: C4.5, CART, k-NN and Naïve Bayes. The performance of these algorithms are compared with accuracy, error rate and average cost on modified versions of NSL-KDD train and test dataset where the instances are classified into normal and four cyber-attack categories: DoS, Probing, R2L and U2R. Additionally the most important features to detect cyber-attacks in all categories and in each category are evaluated with Weka’s Attribute Evaluator and ranked according to Information Gain. The results show that the classification algorithm with best performance on the dataset is the k-NN algorithm. The most important features to detect cyber-attacks are basic features such as the number of seconds of a network connection, the protocol used for the connection, the network service used, normal or error status of the connection and the number of data bytes sent. The most important features to detect DoS, Probing and R2L attacks are basic features and the least important features are content features. Unlike U2R attacks, where the content features are the most important features to detect attacks.