Scaling Laws and Similarity Detection in Sequence Alignment with Gaps

We study the problem of similarity detection by sequence alignment with gaps, using a recently established theoretical framework based on the morphology of alignment paths. Alignments of sequences without mutual correlations are found to have scale-invariant statistics. This is the basis for a scaling theory of alignments of correlated sequences. Using a simple Markov model of evolution, we generate sequences with well-defined mutual correlations and quantify the fidelity of an alignment in an unambiguous way. The scaling theory predicts the dependence of the fidelity on the alignment parameters and on the statistical evolution parameters characterizing the sequence correlations. Specific criteria for the optimal choice of alignment parameters emerge from this theory. The results are verified by extensive numerical simulations.Comment: 25 pages, 11 figure

The Quaternion-Based Spatial Coordinate and Orientation Frame Alignment Problems

We review the general problem of finding a global rotation that transforms a given set of points and/or coordinate frames (the "test" data) into the best possible alignment with a corresponding set (the "reference" data). For 3D point data, this "orthogonal Procrustes problem" is often phrased in terms of minimizing a root-mean-square deviation or RMSD corresponding to a Euclidean distance measure relating the two sets of matched coordinates. We focus on quaternion eigensystem methods that have been exploited to solve this problem for at least five decades in several different bodies of scientific literature where they were discovered independently. While numerical methods for the eigenvalue solutions dominate much of this literature, it has long been realized that the quaternion-based RMSD optimization problem can also be solved using exact algebraic expressions based on the form of the quartic equation solution published by Cardano in 1545; we focus on these exact solutions to expose the structure of the entire eigensystem for the traditional 3D spatial alignment problem. We then explore the structure of the less-studied orientation data context, investigating how quaternion methods can be extended to solve the corresponding 3D quaternion orientation frame alignment (QFA) problem, noting the interesting equivalence of this problem to the rotation-averaging problem, which also has been the subject of independent literature threads. We conclude with a brief discussion of the combined 3D translation-orientation data alignment problem. Appendices are devoted to a tutorial on quaternion frames, a related quaternion technique for extracting quaternions from rotation matrices, and a review of quaternion rotation-averaging methods relevant to the orientation-frame alignment problem. Supplementary Material covers extensions of quaternion methods to the 4D problem.Comment: This replaces an early draft that lacked a number of important references to previous work. There are also additional graphics elements. The extensions to 4D data and additional details are worked out in the Supplementary Material appended to the main tex

Convex Graph Invariant Relaxations For Graph Edit Distance

The edit distance between two graphs is a widely used measure of similarity that evaluates the smallest number of vertex and edge deletions/insertions required to transform one graph to another. It is NP-hard to compute in general, and a large number of heuristics have been proposed for approximating this quantity. With few exceptions, these methods generally provide upper bounds on the edit distance between two graphs. In this paper, we propose a new family of computationally tractable convex relaxations for obtaining lower bounds on graph edit distance. These relaxations can be tailored to the structural properties of the particular graphs via convex graph invariants. Specific examples that we highlight in this paper include constraints on the graph spectrum as well as (tractable approximations of) the stability number and the maximum-cut values of graphs. We prove under suitable conditions that our relaxations are tight (i.e., exactly compute the graph edit distance) when one of the graphs consists of few eigenvalues. We also validate the utility of our framework on synthetic problems as well as real applications involving molecular structure comparison problems in chemistry.Comment: 27 pages, 7 figure

On the Complexity of BWT-Runs Minimization via Alphabet Reordering

The Burrows-Wheeler Transform (BWT) has been an essential tool in text compression and indexing. First introduced in 1994, it went on to provide the backbone for the first encoding of the classic suffix tree data structure in space close to the entropy-based lower bound. Recently, there has been the development of compact suffix trees in space proportional to "$r$", the number of runs in the BWT, as well as the appearance of $r$ in the time complexity of new algorithms. Unlike other popular measures of compression, the parameter $r$ is sensitive to the lexicographic ordering given to the text's alphabet. Despite several past attempts to exploit this, a provably efficient algorithm for finding, or approximating, an alphabet ordering which minimizes $r$ has been open for years. We present the first set of results on the computational complexity of minimizing BWT-runs via alphabet reordering. We prove that the decision version of this problem is NP-complete and cannot be solved in time $2^{o(\sigma + \sqrt{n})}$ unless the Exponential Time Hypothesis fails, where $\sigma$ is the size of the alphabet and $n$ is the length of the text. We also show that the optimization problem is APX-hard. In doing so, we relate two previously disparate topics: the optimal traveling salesperson path and the number of runs in the BWT of a text, providing a surprising connection between problems on graphs and text compression. Also, by relating recent results in the field of dictionary compression, we illustrate that an arbitrary alphabet ordering provides a $O(\log^2 n)$-approximation. We provide an optimal linear-time algorithm for the problem of finding a run minimizing ordering on a subset of symbols (occurring only once) under ordering constraints, and prove a generalization of this problem to a class of graphs with BWT like properties called Wheeler graphs is NP-complete

Positive Definite Kernels in Machine Learning

This survey is an introduction to positive definite kernels and the set of methods they have inspired in the machine learning literature, namely kernel methods. We first discuss some properties of positive definite kernels as well as reproducing kernel Hibert spaces, the natural extension of the set of functions $\{k(x,\cdot),x\in\mathcal{X}\}$ associated with a kernel $k$ defined on a space $\mathcal{X}$. We discuss at length the construction of kernel functions that take advantage of well-known statistical models. We provide an overview of numerous data-analysis methods which take advantage of reproducing kernel Hilbert spaces and discuss the idea of combining several kernels to improve the performance on certain tasks. We also provide a short cookbook of different kernels which are particularly useful for certain data-types such as images, graphs or speech segments.Comment: draft. corrected a typo in figure

ReDO: Cross-Layer Multi-Objective Design-Exploration Framework for Efficient Soft Error Resilient Systems

Designing soft errors resilient systems is a complex engineering task, which nowadays follows a cross-layer approach. It requires a careful planning for different fault-tolerance mechanisms at different system's layers: starting from the technology up to the software domain. While these design decisions have a positive effect on the reliability of the system, they usually have a detrimental effect on its size, power consumption, performance and cost. Design space exploration for cross-layer reliability is therefore a multi-objective search problem in which reliability must be traded-off with other design dimensions. This paper proposes a cross-layer multi-objective design space exploration algorithm developed to help designers when building soft error resilient electronic systems. The algorithm exploits a system-level Bayesian reliability estimation model to analyze the effect of different cross-layer combinations of protection mechanisms on the reliability of the full system. A new heuristic based on the extremal optimization theory is used to efficiently explore the design space. An extended set of simulations shows the capability of this framework when applied both to benchmark applications and realistic systems, providing optimized systems that outperform those obtained by applying state-of-the-art cross-layer reliability techniques

A Probabilistic Model of Local Sequence Alignment That Simplifies Statistical Significance Estimation

Sequence database searches require accurate estimation of the statistical significance of scores. Optimal local sequence alignment scores follow Gumbel distributions, but determining an important parameter of the distribution (λ) requires time-consuming computational simulation. Moreover, optimal alignment scores are less powerful than probabilistic scores that integrate over alignment uncertainty (“Forward” scores), but the expected distribution of Forward scores remains unknown. Here, I conjecture that both expected score distributions have simple, predictable forms when full probabilistic modeling methods are used. For a probabilistic model of local sequence alignment, optimal alignment bit scores (“Viterbi” scores) are Gumbel-distributed with constant λ = log 2, and the high scoring tail of Forward scores is exponential with the same constant λ. Simulation studies support these conjectures over a wide range of profile/sequence comparisons, using 9,318 profile-hidden Markov models from the Pfam database. This enables efficient and accurate determination of expectation values (E-values) for both Viterbi and Forward scores for probabilistic local alignments