Fast matching statistics in small space

Computing the matching statistics of a string S with respect to a string T on an alphabet of size sigma is a fundamental primitive for a number of large-scale string analysis applications, including the comparison of entire genomes, for which space is a pressing issue. This paper takes from theory to practice an existing algorithm that uses just O(|T|log{sigma}) bits of space, and that computes a compact encoding of the matching statistics array in O(|S|log{sigma}) time. The techniques used to speed up the algorithm are of general interest, since they optimize queries on the existence of a Weiner link from a node of the suffix tree, and parent operations after unsuccessful Weiner links. Thus, they can be applied to other matching statistics algorithms, as well as to any suffix tree traversal that relies on such calls. Some of our optimizations yield a matching statistics implementation that is up to three times faster than a plain version of the algorithm, depending on the similarity between S and T. In genomic datasets of practical significance we achieve speedups of up to 1.8, but our fastest implementations take on average twice the time of an existing code based on the LCP array. The key advantage is that our implementations need between one half and one fifth of the competitor\u27s memory, and they approach comparable running times when S and T are very similar

Managing Compressed Structured Text

[Definition]: Compressing structured text is the problem of creating a reduced-space representation from which the original data can be re-created exactly. Compared to plain text compression, the goal is to take advantage of the structural properties of the data. A more ambitious goal is that of being able of manipulating this text in compressed form, without decompressing it. This entry focuses on compressing, navigating, and searching structured text, as those are the areas where more advances have been made

Compressing and Performing Algorithms on Massively Large Networks

Networks are represented as a set of nodes (vertices) and the arcs (links) connecting them. Such networks can model various real-world structures such as social networks (e.g., Facebook), information networks (e.g., citation networks), technological networks (e.g., the Internet), and biological networks (e.g., gene-phenotype network). Analysis of such structures is a heavily studied area with many applications. However, in this era of big data, we find ourselves with networks so massive that the space requirements inhibit network analysis. Since many of these networks have nodes and arcs on the order of billions to trillions, even basic data structures such as adjacency lists could cost petabytes to zettabytes of storage. Storing these networks in secondary memory would require I/O access (i.e., disk access) during analysis, thus drastically slowing analysis time. To perform analysis efficiently on such extensive data, we either need enough main memory for the data structures and algorithms, or we need to develop compressions that require much less space while still being able to answer queries efficiently. In this dissertation, we develop several compression techniques that succinctly represent these real-world networks while still being able to efficiently query the network (e.g., check if an arc exists between two nodes). Furthermore, since many of these networks continue to grow over time, our compression techniques also support the ability to add and remove nodes and edges directly on the compressed structure. We also provide a way to compress the data quickly without any intermediate structure, thus giving minimal memory overhead. We provide detailed analysis and prove that our compression is indeed succinct (i.e., achieves the information-theoretic lower bound). Also, we empirically show that our compression rates outperform or are equal to existing compression algorithms on many benchmark datasets. We also extend our technique to time-evolving networks. That is, we store the entire state of the network at each time frame. Studying time-evolving networks allows us to find patterns throughout the time that would not be available in regular, static network analysis. A succinct representation for time-evolving networks is arguably more important than static graphs, due to the extra dimension inflating the space requirements of basic data structures even more. Again, we manage to achieve succinctness while also providing fast encoding, minimal memory overhead during encoding, fast queries, and fast, direct modification. We also compare against several benchmarks and empirically show that we achieve compression rates better than or equal to the best performing benchmark for each dataset. Finally, we also develop both static and time-evolving algorithms that run directly on our compressed structures. Using our static graph compression combined with our differential technique, we find that we can speed up matrix-vector multiplication by reusing previously computed products. We compare our results against a similar technique using the Webgraph Framework, and we see that not only are our base query speeds faster, but we also gain a more significant speed-up from reusing products. Then, we use our time-evolving compression to solve the earliest arrival paths problem and time-evolving transitive closure. We found that not only were we the first to run such algorithms directly on compressed data, but that our technique was particularly efficient at doing so

Parallel and scalable combinatorial string algorithms on distributed memory systems

Methods for processing and analyzing DNA and genomic data are built upon combinatorial graph and string algorithms. The advent of high-throughput DNA sequencing is enabling the generation of billions of reads per experiment. Classical and sequential algorithms can no longer deal with these growing data sizes - which for the last 10 years have greatly out-paced advances in processor speeds. Processing and analyzing state-of-the-art genomic data sets require the design of scalable and efficient parallel algorithms and the use of large computing clusters. Suffix arrays and trees are fundamental string data structures, which lie at the foundation of many string algorithms, with important applications in text processing, information retrieval, and computational biology. Conversely, the parallel construction of these indices is an actively studied problem. However, prior approaches lacked good worst-case run-time guarantees and exhibit poor scaling and overall performance. In this work, we present our distributed-memory parallel algorithms for indexing large datasets, including algorithms for the distributed construction of suffix arrays, LCP arrays, and suffix trees. We formulate a generalized version of the All-Nearest-Smaller-Values problem, provide an optimal distributed solution, and apply it to the distributed construction of suffix trees - yielding a work-optimal parallel algorithm. Our algorithms for distributed suffix array and suffix tree construction improve the state-of-the-art by simultaneously improving worst-case run-time bounds and achieving superior practical performance. Next, we introduce a novel distributed string index, the Distributed Enhanced Suffix Array (DESA) - based on the suffix and LCP arrays, the DESA consists of these and additional distributed data structures. The DESA is designed to allow efficient pattern search queries in distributed memory while requiring at most O(n/p) memory per process. We present efficient distributed-memory parallel algorithms for querying, as well as for the efficient construction of this distributed index. Finally, we present our work on distributed-memory algorithms for clustering de Bruijn graphs and its application to solving a grand challenge metagenomic dataset.Ph.D

GRAPES-DD: exploiting decision diagrams for index-driven search in biological graph databases

BACKGROUND: Graphs are mathematical structures widely used for expressing relationships among elements when representing biomedical and biological information. On top of these representations, several analyses are performed. A common task is the search of one substructure within one graph, called target. The problem is referred to as one-to-one subgraph search, and it is known to be NP-complete. Heuristics and indexing techniques can be applied to facilitate the search. Indexing techniques are also exploited in the context of searching in a collection of target graphs, referred to as one-to-many subgraph problem. Filter-and-verification methods that use indexing approaches provide a fast pruning of target graphs or parts of them that do not contain the query. The expensive verification phase is then performed only on the subset of promising targets. Indexing strategies extract graph features at a sufficient granularity level for performing a powerful filtering step. Features are memorized in data structures allowing an efficient access. Indexing size, querying time and filtering power are key points for the development of efficient subgraph searching solutions.RESULTS: An existing approach, GRAPES, has been shown to have good performance in terms of speed-up for both one-to-one and one-to-many cases. However, it suffers in the size of the built index. For this reason, we propose GRAPES-DD, a modified version of GRAPES in which the indexing structure has been replaced with a Decision Diagram. Decision Diagrams are a broad class of data structures widely used to encode and manipulate functions efficiently. Experiments on biomedical structures and synthetic graphs have confirmed our expectation showing that GRAPES-DD has substantially reduced the memory utilization compared to GRAPES without worsening the searching time.CONCLUSION: The use of Decision Diagrams for searching in biochemical and biological graphs is completely new and potentially promising thanks to their ability to encode compactly sets by exploiting their structure and regularity, and to manipulate entire sets of elements at once, instead of exploring each single element explicitly. Search strategies based on Decision Diagram makes the indexing for biochemical graphs, and not only, more affordable allowing us to potentially deal with huge and ever growing collections of biochemical and biological structures

Graphical pangenomics

Completely sequencing genomes is expensive, and to save costs we often analyze new genomic data in the context of a reference genome. This approach distorts our image of the inferred genome, an effect which we describe as reference bias. To mitigate reference bias, I repurpose graphical models previously used in genome assembly and alignment to serve as a reference system in resequencing. To do so I formalize the concept of a variation graph to link genomes to a graphical model of their mutual alignment that is capable of representing any kind of genomic variation, both small and large. As this model combines both sequence and variation information in one structure it serves as a natural basis for resequencing. By indexing the topology, sequence space, and haplotype space of these graphs and developing generalizations of sequence alignment suitable to them, I am able to use them as reference systems in the analysis of a wide array of genomic systems, from large vertebrate genomes to microbial pangenomes. To demonstrate the utility of this approach, I use my implementation to solve resequencing and alignment problems in the context of Homo sapiens and Saccharomyces cerevisiae. I use graph visualization techniques to explore variation graphs built from a variety of sources, including diverged human haplotypes, a gut microbiome, and a freshwater viral metagenome. I find that variation aware read alignment can eliminate reference bias at known variants, and this is of particular importance in the analysis of ancient DNA, where existing approaches result in significant bias towards the reference genome and concomitant distortion of population genetics results. I validate that the variation graph model can be applied to align RNA sequencing data to a splicing graph. Finally, I show that a classical pangenomic inference problem in microbiology can be solved using a resequencing approach based on variation graphs.Wellcome Trust PhD fellowshi