Identification of functionally related enzymes by learning-to-rank methods

Enzyme sequences and structures are routinely used in the biological sciences as queries to search for functionally related enzymes in online databases. To this end, one usually departs from some notion of similarity, comparing two enzymes by looking for correspondences in their sequences, structures or surfaces. For a given query, the search operation results in a ranking of the enzymes in the database, from very similar to dissimilar enzymes, while information about the biological function of annotated database enzymes is ignored. In this work we show that rankings of that kind can be substantially improved by applying kernel-based learning algorithms. This approach enables the detection of statistical dependencies between similarities of the active cleft and the biological function of annotated enzymes. This is in contrast to search-based approaches, which do not take annotated training data into account. Similarity measures based on the active cleft are known to outperform sequence-based or structure-based measures under certain conditions. We consider the Enzyme Commission (EC) classification hierarchy for obtaining annotated enzymes during the training phase. The results of a set of sizeable experiments indicate a consistent and significant improvement for a set of similarity measures that exploit information about small cavities in the surface of enzymes

Enumerating Maximal Bicliques from a Large Graph Using MapReduce

We consider the enumeration of maximal bipartite cliques (bicliques) from a large graph, a task central to many data mining problems arising in social network analysis and bioinformatics. We present novel parallel algorithms for the MapReduce framework, and an experimental evaluation using Hadoop MapReduce. Our algorithm is based on clustering the input graph into smaller subgraphs, followed by processing different subgraphs in parallel. Our algorithm uses two ideas that enable it to scale to large graphs: (1) the redundancy in work between different subgraph explorations is minimized through a careful pruning of the search space, and (2) the load on different reducers is balanced through a task assignment that is based on an appropriate total order among the vertices. We show theoretically that our algorithm is work optimal, i.e., it performs the same total work as its sequential counterpart. We present a detailed evaluation which shows that the algorithm scales to large graphs with millions of edges and tens of millions of maximal bicliques. To our knowledge, this is the first work on maximal biclique enumeration for graphs of this scale

Doctor of Philosophy

dissertationServing as a record of what happened during a scientific process, often computational, provenance has become an important piece of computing. The importance of archiving not only data and results but also the lineage of these entities has led to a variety of systems that capture provenance as well as models and schemas for this information. Despite significant work focused on obtaining and modeling provenance, there has been little work on managing and using this information. Using the provenance from past work, it is possible to mine common computational structure or determine differences between executions. Such information can be used to suggest possible completions for partial workflows, summarize a set of approaches, or extend past work in new directions. These applications require infrastructure to support efficient queries and accessible reuse. In order to support knowledge discovery and reuse from provenance information, the management of those data is important. One component of provenance is the specification of the computations; workflows provide structured abstractions of code and are commonly used for complex tasks. Using change-based provenance, it is possible to store large numbers of similar workflows compactly. This storage also allows efficient computation of differences between specifications. However, querying for specific structure across a large collection of workflows is difficult because comparing graphs depends on computing subgraph isomorphism which is NP-Complete. Graph indexing methods identify features that help distinguish graphs of a collection to filter results for a subgraph containment query and reduce the number of subgraph isomorphism computations. For provenance, this work extends these methods to work for more exploratory queries and collections with significant overlap. However, comparing workflow or provenance graphs may not require exact equality; a match between two graphs may allow paired nodes to be similar yet not equivalent. This work presents techniques to better correlate graphs to help summarize collections. Using this infrastructure, provenance can be reused so that users can learn from their own and others' history. Just as textual search has been augmented with suggested completions based on past or common queries, provenance can be used to suggest how computations can be completed or which steps might connect to a given subworkflow. In addition, provenance can help further science by accelerating publication and reuse. By incorporating provenance into publications, authors can more easily integrate their results, and readers can more easily verify and repeat results. However, reusing past computations requires maintaining stronger associations with any input data and underlying code as well as providing paths for migrating old work to new hardware or algorithms. This work presents a framework for maintaining data and code as well as supporting upgrades for workflow computations

Topological network alignment uncovers biological function and phylogeny

Sequence comparison and alignment has had an enormous impact on our understanding of evolution, biology, and disease. Comparison and alignment of biological networks will likely have a similar impact. Existing network alignments use information external to the networks, such as sequence, because no good algorithm for purely topological alignment has yet been devised. In this paper, we present a novel algorithm based solely on network topology, that can be used to align any two networks. We apply it to biological networks to produce by far the most complete topological alignments of biological networks to date. We demonstrate that both species phylogeny and detailed biological function of individual proteins can be extracted from our alignments. Topology-based alignments have the potential to provide a completely new, independent source of phylogenetic information. Our alignment of the protein-protein interaction networks of two very different species--yeast and human--indicate that even distant species share a surprising amount of network topology with each other, suggesting broad similarities in internal cellular wiring across all life on Earth.Comment: Algorithm explained in more details. Additional analysis adde

Socio-Cognitive and Affective Computing

Social cognition focuses on how people process, store, and apply information about other people and social situations. It focuses on the role that cognitive processes play in social interactions. On the other hand, the term cognitive computing is generally used to refer to new hardware and/or software that mimics the functioning of the human brain and helps to improve human decision-making. In this sense, it is a type of computing with the goal of discovering more accurate models of how the human brain/mind senses, reasons, and responds to stimuli. Socio-Cognitive Computing should be understood as a set of theoretical interdisciplinary frameworks, methodologies, methods and hardware/software tools to model how the human brain mediates social interactions. In addition, Affective Computing is the study and development of systems and devices that can recognize, interpret, process, and simulate human affects, a fundamental aspect of socio-cognitive neuroscience. It is an interdisciplinary field spanning computer science, electrical engineering, psychology, and cognitive science. Physiological Computing is a category of technology in which electrophysiological data recorded directly from human activity are used to interface with a computing device. This technology becomes even more relevant when computing can be integrated pervasively in everyday life environments. Thus, Socio-Cognitive and Affective Computing systems should be able to adapt their behavior according to the Physiological Computing paradigm. This book integrates proposals from researchers who use signals from the brain and/or body to infer people's intentions and psychological state in smart computing systems. The design of this kind of systems combines knowledge and methods of ubiquitous and pervasive computing, as well as physiological data measurement and processing, with those of socio-cognitive and affective computing

Structural Graph-based Metamodel Matching

Data integration has been, and still is, a challenge for applications processing multiple heterogeneous data sources. Across the domains of schemas, ontologies, and metamodels, this imposes the need for mapping specifications, i.e. the task of discovering semantic correspondences between elements. Support for the development of such mappings has been researched, producing matching systems that automatically propose mapping suggestions. However, especially in the context of metamodel matching the result quality of state of the art matching techniques leaves room for improvement. Although the traditional approach of pair-wise element comparison works on smaller data sets, its quadratic complexity leads to poor runtime and memory performance and eventually to the inability to match, when applied on real-world data. The work presented in this thesis seeks to address these shortcomings. Thereby, we take advantage of the graph structure of metamodels. Consequently, we derive a planar graph edit distance as metamodel similarity metric and mining-based matching to make use of redundant information. We also propose a planar graph-based partitioning to cope with large-scale matching. These techniques are then evaluated using real-world mappings from SAP business integration scenarios and the MDA community. The results demonstrate improvement in quality and managed runtime and memory consumption for large-scale metamodel matching