Hyperplane Arrangements and Locality-Sensitive Hashing with Lift

Locality-sensitive hashing converts high-dimensional feature vectors, such as image and speech, into bit arrays and allows high-speed similarity calculation with the Hamming distance. There is a hashing scheme that maps feature vectors to bit arrays depending on the signs of the inner products between feature vectors and the normal vectors of hyperplanes placed in the feature space. This hashing can be seen as a discretization of the feature space by hyperplanes. If labels for data are given, one can determine the hyperplanes by using learning algorithms. However, many proposed learning methods do not consider the hyperplanes' offsets. Not doing so decreases the number of partitioned regions, and the correlation between Hamming distances and Euclidean distances becomes small. In this paper, we propose a lift map that converts learning algorithms without the offsets to the ones that take into account the offsets. With this method, the learning methods without the offsets give the discretizations of spaces as if it takes into account the offsets. For the proposed method, we input several high-dimensional feature data sets and studied the relationship between the statistical characteristics of data, the number of hyperplanes, and the effect of the proposed method.Comment: 9 pages, 7 figure

Software for supporting large scale data processing for High Throughput Screening

High Throughput Screening for is a valuable data generation technique for data driven knowledge discovery. Because the rate of data generation is so great, it is a challenge to cope with the demands of post experiment data analysis. This thesis presents three software solutions that I implemented in an attempt to alleviate this problem. The first is K-Screen, a Laboratory Information Management System designed to handle and visualize large High Throughput Screening datasets. K-Screen is being successfully used by the University of Kansas High Throughput Screening Laboratory to better organize and visualize their data. The next two algorithms are designed to accelerate the search times for chemical similarity searches using 1-dimensional fingerprints. The first algorithm balances information content in bit strings to attempt to find more optimal ordering and segmentation patterns for chemical fingerprints. The second algorithm eliminates redundant pruning calculations for large batch chemical similarity searches and shows a 250% improvement for the fastest current fingerprint search algorithm for large batch queries

A Combined Approach For Private Indexing Mechanism

Private indexing is a set of approaches for analyzing research data that are similar or resemble similar ones. This is used in the database to keep track of the keys and their values. The main subject of this research is private indexing in record linkage to secure the data. Because unique personal identification numbers or social security numbers are not accessible in most countries or databases, data linkage is limited to attributes such as date of birth and names to distinguish between the number of records and the real-life entities they represent. For security reasons, the encryption of these identifiers is required. Privacy-preserving record linkage, frequently used to link private data within several databases from different companies, prevents sensitive information from being exposed to other companies. This research used a combined method to evaluate the data, using classic and new indexing methods. A combined approach is more secure than typical standard indexing in terms of privacy. Multibit tree indexing, which groups comparable data in many ways, creates a scalable tree-like structure that is both space and time flexible, as it avoids the need for redundant block structures. Because the record pair numbers to compare are the Cartesian product of both the file record numbers, the work required grows with the number of records to compare in the files. The evaluation findings of this research showed that combined method is scalable in terms of the number of databases to be linked, the database size, and the time required

Read alignment using deep neural networks

2019 Spring.Includes bibliographical references.Read alignment is the process of mapping short DNA sequences into the reference genome. With the advent of consecutively evolving "next generation" sequencing technologies, the need for sequence alignment tools appeared. Many scientific communities and the companies marketing the sequencing technologies developed a whole spectrum of read aligners/mappers for different error profiles and read length characteristics. Among the most recent successfully marketed sequencing technologies are Oxford Nanopore and PacBio SMRT sequencing, which are considered top players because of their extremely long reads and low cost. However, the reads may contain error up to 20% that are not generally uniformly distributed. To deal with that level of error rate and read length, proximity preserving hashing techniques, such as Minhash and Minimizers, were utilized to quickly map a read to the target region of the reference sequence. Subsequently, a variant of global or local alignment dynamic programming is then used to give the final alignment. In this research work, we train a Deep Neural Network (DNN) to yield a hashing scheme for the highly erroneous long reads, which is deemed superior to Minhash for mapping the reads. We implemented that idea to build a read alignment tool: DNNAligner. We evaluated the performance of our aligner against the popular read aligners in the bioinformatics community currently — minimap2, bwa-mem and graphmap. Our results show that the performance of DNNAligner is comparable to other tools without any code optimization or integration of other advanced features. Moreover, DNN exhibits superior performance in comparison with Minhashon neighborhood classification

Graph-Based Approaches to Protein StructureComparison - From Local to Global Similarity

The comparative analysis of protein structure data is a central aspect of structural bioinformatics. Drawing upon structural information allows the inference of function for unknown proteins even in cases where no apparent homology can be found on the sequence level. Regarding the function of an enzyme, the overall fold topology might less important than the specific structural conformation of the catalytic site or the surface region of a protein, where the interaction with other molecules, such as binding partners, substrates and ligands occurs. Thus, a comparison of these regions is especially interesting for functional inference, since structural constraints imposed by the demands of the catalyzed biochemical function make them more likely to exhibit structural similarity. Moreover, the comparative analysis of protein binding sites is of special interest in pharmaceutical chemistry, in order to predict cross-reactivities and gain a deeper understanding of the catalysis mechanism. From an algorithmic point of view, the comparison of structured data, or, more generally, complex objects, can be attempted based on different methodological principles. Global methods aim at comparing structures as a whole, while local methods transfer the problem to multiple comparisons of local substructures. In the context of protein structure analysis, it is not a priori clear, which strategy is more suitable. In this thesis, several conceptually different algorithmic approaches have been developed, based on local, global and semi-global strategies, for the task of comparing protein structure data, more specifically protein binding pockets. The use of graphs for the modeling of protein structure data has a long standing tradition in structural bioinformatics. Recently, graphs have been used to model the geometric constraints of protein binding sites. The algorithms developed in this thesis are based on this modeling concept, hence, from a computer scientist's point of view, they can also be regarded as global, local and semi-global approaches to graph comparison. The developed algorithms were mainly designed on the premise to allow for a more approximate comparison of protein binding sites, in order to account for the molecular flexibility of the protein structures. A main motivation was to allow for the detection of more remote similarities, which are not apparent by using more rigid methods. Subsequently, the developed approaches were applied to different problems typically encountered in the field of structural bioinformatics in order to assess and compare their performance and suitability for different problems. Each of the approaches developed during this work was capable of improving upon the performance of existing methods in the field. Another major aspect in the experiments was the question, which methodological concept, local, global or a combination of both, offers the most benefits for the specific task of protein binding site comparison, a question that is addressed throughout this thesis

Binding site matching in rational drug design: Algorithms and applications

© 2018 The Author(s) 2018. Published by Oxford University Press. All rights reserved. Interactions between proteins and small molecules are critical for biological functions. These interactions often occur in small cavities within protein structures, known as ligand-binding pockets. Understanding the physicochemical qualities of binding pockets is essential to improve not only our basic knowledge of biological systems, but also drug development procedures. In order to quantify similarities among pockets in terms of their geometries and chemical properties, either bound ligands can be compared to one another or binding sites can be matched directly. Both perspectives routinely take advantage of computational methods including various techniques to represent and compare small molecules as well as local protein structures. In this review, we survey 12 tools widely used to match pockets. These methods are divided into five categories based on the algorithm implemented to construct binding-site alignments. In addition to the comprehensive analysis of their algorithms, test sets and the performance of each method are described. We also discuss general pharmacological applications of computational pocket matching in drug repurposing, polypharmacology and side effects. Reflecting on the importance of these techniques in drug discovery, in the end, we elaborate on the development of more accurate meta-predictors, the incorporation of protein flexibility and the integration of powerful artificial intelligence technologies such as deep learning

Detection and management of redundancy for information retrieval

The growth of the web, authoring software, and electronic publishing has led to the emergence of a new type of document collection that is decentralised, amorphous, dynamic, and anarchic. In such collections, redundancy is a significant issue. Documents can spread and propagate across such collections without any control or moderation. Redundancy can interfere with the information retrieval process, leading to decreased user amenity in accessing information from these collections, and thus must be effectively managed. The precise definition of redundancy varies with the application. We restrict ourselves to documents that are co-derivative: those that share a common heritage, and hence contain passages of common text. We explore document fingerprinting, a well-known technique for the detection of co-derivative document pairs. Our new lossless fingerprinting algorithm improves the effectiveness of a range of document fingerprinting approaches. We empirically show that our algorithm can be highly effective at discovering co-derivative document pairs in large collections. We study the occurrence and management of redundancy in a range of application domains. On the web, we find that document fingerprinting is able to identify widespread redundancy, and that this redundancy has a significant detrimental effect on the quality of search results. Based on user studies, we suggest that redundancy is most appropriately managed as a postprocessing step on the ranked list and explain how and why this should be done. In the genomic area of sequence homology search, we explain why the existing techniques for redundancy discovery are increasingly inefficient, and present a critique of the current approaches to redundancy management. We show how document fingerprinting with a modified version of our algorithm provides significant efficiency improvements, and propose a new approach to redundancy management based on wildcards. We demonstrate that our scheme provides the benefits of existing techniques but does not have their deficiencies. Redundancy in distributed information retrieval systems - where different parts of the collection are searched by autonomous servers - cannot be effectively managed using traditional fingerprinting techniques. We thus propose a new data structure, the grainy hash vector, for redundancy detection and management in this environment. We show in preliminary tests that the grainy hash vector is able to accurately detect a good proportion of redundant document pairs while maintaining low resource usage

Cheminformatics Tools to Explore the Chemical Space of Peptides and Natural Products

Cheminformatics facilitates the analysis, storage, and collection of large quantities of chemical data, such as molecular structures and molecules' properties and biological activity, and it has revolutionized medicinal chemistry for small molecules. However, its application to larger molecules is still underrepresented. This thesis work attempts to fill this gap and extend the cheminformatics approach towards large molecules and peptides. This thesis is divided into two parts. The first part presents the implementation and application of two new molecular descriptors: macromolecule extended atom pair fingerprint (MXFP) and MinHashed atom pair fingerprint of radius 2 (MAP4). MXFP is an atom pair fingerprint suitable for large molecules, and here, it is used to explore the chemical space of non-Lipinski molecules within the widely used PubChem and ChEMBL databases. MAP4 is a MinHashed hybrid of substructure and atom pair fingerprints suitable for encoding small and large molecules. MAP4 is first benchmarked against commonly used atom pairs and substructure fingerprints, and then it is used to investigate the chemical space of microbial and plants natural products with the aid of machine learning and chemical space mapping. The second part of the thesis focuses on peptides, and it is introduced by a review chapter on approaches to discover novel peptide structures and describing the known peptide chemical space. Then, a genetic algorithm that uses MXFP in its fitness function is described and challenged to generate peptide analogs of peptidic or non-peptidic queries. Finally, supervised and unsupervised machine learning is used to generate novel antimicrobial and non-hemolytic peptide sequences