Multipartite Graph Algorithms for the Analysis of Heterogeneous Data

The explosive growth in the rate of data generation in recent years threatens to outpace the growth in computer power, motivating the need for new, scalable algorithms and big data analytic techniques. No field may be more emblematic of this data deluge than the life sciences, where technologies such as high-throughput mRNA arrays and next generation genome sequencing are routinely used to generate datasets of extreme scale. Data from experiments in genomics, transcriptomics, metabolomics and proteomics are continuously being added to existing repositories. A goal of exploratory analysis of such omics data is to illuminate the functions and relationships of biomolecules within an organism. This dissertation describes the design, implementation and application of graph algorithms, with the goal of seeking dense structure in data derived from omics experiments in order to detect latent associations between often heterogeneous entities, such as genes, diseases and phenotypes. Exact combinatorial solutions are developed and implemented, rather than relying on approximations or heuristics, even when problems are exceedingly large and/or difficult. Datasets on which the algorithms are applied include time series transcriptomic data from an experiment on the developing mouse cerebellum, gene expression data measuring acute ethanol response in the prefrontal cortex, and the analysis of a predicted protein-protein interaction network. A bipartite graph model is used to integrate heterogeneous data types, such as genes with phenotypes and microbes with mouse strains. The techniques are then extended to a multipartite algorithm to enumerate dense substructure in multipartite graphs, constructed using data from three or more heterogeneous sources, with applications to functional genomics. Several new theoretical results are given regarding multipartite graphs and the multipartite enumeration algorithm. In all cases, practical implementations are demonstrated to expand the frontier of computational feasibility

Cohesive subgraph identification in large graphs

Graph data is ubiquitous in real world applications, as the relationship among entities in the applications can be naturally captured by the graph model. Finding cohesive subgraphs is a fundamental problem in graph mining with diverse applications. Given the important roles of cohesive subgraphs, this thesis focuses on cohesive subgraph identification in large graphs. Firstly, we study the size-bounded community search problem that aims to find a subgraph with the largest min-degree among all connected subgraphs that contain the query vertex q and have at least l and at most h vertices, where q, l, h are specified by the query. As the problem is NP-hard, we propose a branch-reduce-and-bound algorithm SC-BRB by developing nontrivial reducing techniques, upper bounding techniques, and branching techniques. Secondly, we formulate the notion of similar-biclique in bipartite graphs which is a special kind of biclique where all vertices from a designated side are similar to each other, and aim to enumerate all maximal similar-bicliques. We propose a backtracking algorithm MSBE to directly enumerate maximal similar-bicliques, and power it by vertex reduction and optimization techniques. In addition, we design a novel index structure to speed up a time-critical operation of MSBE, as well as to speed up vertex reduction. Efficient index construction algorithms are developed. Thirdly, we consider balanced cliques in signed graphs --- a clique is balanced if its vertex set can be partitioned into CL and CR such that all negative edges are between CL and CR --- and study the problem of maximum balanced clique computation. We propose techniques to transform the maximum balanced clique problem over G to a series of maximum dichromatic clique problems over small subgraphs of G. The transformation not only removes edge signs but also sparsifies the edge set

Transcriptomic Data Analysis Using Graph-Based Out-of-Core Methods

Biological data derived from high-throughput microarrays can be transformed into finite, simple, undirected graphs and analyzed using tools first introduced by the Langston Lab at the University of Tennessee. Transforming raw data can be broken down into three main tasks: data normalization, generation of similarity metrics, and threshold selection. The choice of methods used in each of these steps effect the final outcome of the graph, with respect to size, density, and structure. A number of different algorithms are examined and analyzed to illustrate the magnitude of the effects. Graph-based tools are then used to extract putative gene networks. These tools are loosely based on the concept of clique, which generates clusters optimized for density. Innovative additions to the paraclique algorithm, developed at the Langston Lab, are introduced to generate results that have highest average correlation or highest density. A new suite of algorithms is then presented that exploits the use of a priori gene interactions. Aptly named the anchored analysis toolkit, these algorithms use known interactions as anchor points for generating subgraphs, which are then analyzed for their graph structure. This results in clusters that might have otherwise been lost in noise. A main product of this thesis is a novel collection of algorithms to generate exact solutions to the maximum clique problem for graphs that are too large to fit within core memory. No other algorithms are currently known that produce exact solutions to this problem for extremely large graphs. A combination of in-core and out-of-core techniques is used in conjunction with a distributed-memory programming model. These algorithms take into consideration such pitfalls as external disk I/O and hardware failure and recovery. Finally, a web-based tool is described that provides researchers access the aforementioned algorithms. The Graph Algorithms Pipeline for Pathway Analysis tool, GrAPPA, was previously developed by the Langston Lab and provides the software needed to take raw microarray data as input and preprocess, analyze, and post-process it in a single package. GrAPPA also provides access to high-performance computing resources, via the TeraGrid

Methods for protein complex prediction and their contributions towards understanding the organization, function and dynamics of complexes

Complexes of physically interacting proteins constitute fundamental functional units responsible for driving biological processes within cells. A faithful reconstruction of the entire set of complexes is therefore essential to understand the functional organization of cells. In this review, we discuss the key contributions of computational methods developed till date (approximately between 2003 and 2015) for identifying complexes from the network of interacting proteins (PPI network). We evaluate in depth the performance of these methods on PPI datasets from yeast, and highlight challenges faced by these methods, in particular detection of sparse and small or sub- complexes and discerning of overlapping complexes. We describe methods for integrating diverse information including expression profiles and 3D structures of proteins with PPI networks to understand the dynamics of complex formation, for instance, of time-based assembly of complex subunits and formation of fuzzy complexes from intrinsically disordered proteins. Finally, we discuss methods for identifying dysfunctional complexes in human diseases, an application that is proving invaluable to understand disease mechanisms and to discover novel therapeutic targets. We hope this review aptly commemorates a decade of research on computational prediction of complexes and constitutes a valuable reference for further advancements in this exciting area.Comment: 1 Tabl

Extracting and Cleaning RDF Data

The RDF data model has become a prevalent format to represent heterogeneous data because of its versatility. The capability of dismantling information from its native formats and representing it in triple format offers a simple yet powerful way of modelling data that is obtained from multiple sources. In addition, the triple format and schema constraints of the RDF model make the RDF data easy to process as labeled, directed graphs. This graph representation of RDF data supports higher-level analytics by enabling querying using different techniques and querying languages, e.g., SPARQL. Anlaytics that require structured data are supported by transforming the graph data on-the-fly to populate the target schema that is needed for downstream analysis. These target schemas are defined by downstream applications according to their information need. The flexibility of RDF data brings two main challenges. First, the extraction of RDF data is a complex task that may involve domain expertise about the information required to be extracted for different applications. Another significant aspect of analyzing RDF data is its quality, which depends on multiple factors including the reliability of data sources and the accuracy of the extraction systems. The quality of the analysis depends mainly on the quality of the underlying data. Therefore, evaluating and improving the quality of RDF data has a direct effect on the correctness of downstream analytics. This work presents multiple approaches related to the extraction and quality evaluation of RDF data. To cope with the large amounts of data that needs to be extracted, we present DSTLR, a scalable framework to extract RDF triples from semi-structured and unstructured data sources. For rare entities that fall on the long tail of information, there may not be enough signals to support high-confidence extraction. Towards this problem, we present an approach to estimate property values for long tail entities. We also present multiple algorithms and approaches that focus on the quality of RDF data. These include discovering quality constraints from RDF data, and utilizing machine learning techniques to repair errors in RDF data

Solving hard subgraph problems in parallel

This thesis improves the state of the art in exact, practical algorithms for finding subgraphs. We study maximum clique, subgraph isomorphism, and maximum common subgraph problems. These are widely applicable: within computing science, subgraph problems arise in document clustering, computer vision, the design of communication protocols, model checking, compiler code generation, malware detection, cryptography, and robotics; beyond, applications occur in biochemistry, electrical engineering, mathematics, law enforcement, fraud detection, fault diagnosis, manufacturing, and sociology. We therefore consider both the ``pure'' forms of these problems, and variants with labels and other domain-specific constraints. Although subgraph-finding should theoretically be hard, the constraint-based search algorithms we discuss can easily solve real-world instances involving graphs with thousands of vertices, and millions of edges. We therefore ask: is it possible to generate ``really hard'' instances for these problems, and if so, what can we learn? By extending research into combinatorial phase transition phenomena, we develop a better understanding of branching heuristics, as well as highlighting a serious flaw in the design of graph database systems. This thesis also demonstrates how to exploit two of the kinds of parallelism offered by current computer hardware. Bit parallelism allows us to carry out operations on whole sets of vertices in a single instruction---this is largely routine. Thread parallelism, to make use of the multiple cores offered by all modern processors, is more complex. We suggest three desirable performance characteristics that we would like when introducing thread parallelism: lack of risk (parallel cannot be exponentially slower than sequential), scalability (adding more processing cores cannot make runtimes worse), and reproducibility (the same instance on the same hardware will take roughly the same time every time it is run). We then detail the difficulties in guaranteeing these characteristics when using modern algorithmic techniques. Besides ensuring that parallelism cannot make things worse, we also increase the likelihood of it making things better. We compare randomised work stealing to new tailored strategies, and perform experiments to identify the factors contributing to good speedups. We show that whilst load balancing is difficult, the primary factor influencing the results is the interaction between branching heuristics and parallelism. By using parallelism to explicitly offset the commitment made to weak early branching choices, we obtain parallel subgraph solvers which are substantially and consistently better than the best sequential algorithms

Mining Butterflies in Streaming Graphs

This thesis introduces two main-memory systems sGrapp and sGradd for performing the fundamental analytic tasks of biclique counting and concept drift detection over a streaming graph. A data-driven heuristic is used to architect the systems. To this end, initially, the growth patterns of bipartite streaming graphs are mined and the emergence principles of streaming motifs are discovered. Next, the discovered principles are (a) explained by a graph generator called sGrow; and (b) utilized to establish the requirements for efficient, effective, explainable, and interpretable management and processing of streams. sGrow is used to benchmark stream analytics, particularly in the case of concept drift detection. sGrow displays robust realization of streaming growth patterns independent of initial conditions, scale and temporal characteristics, and model configurations. Extensive evaluations confirm the simultaneous effectiveness and efficiency of sGrapp and sGradd. sGrapp achieves mean absolute percentage error up to 0.05/0.14 for the cumulative butterfly count in streaming graphs with uniform/non-uniform temporal distribution and a processing throughput of 1.5 million data records per second. The throughput and estimation error of sGrapp are 160x higher and 0.02x lower than baselines. sGradd demonstrates an improving performance over time, achieves zero false detection rates when there is not any drift and when drift is already detected, and detects sequential drifts in zero to a few seconds after their occurrence regardless of drift intervals

LIPIcs, Volume 274, ESA 2023, Complete Volume

LIPIcs, Volume 274, ESA 2023, Complete Volum