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

Modern considerations for the use of naive Bayes in the supervised classification of genetic sequence data

2021 Spring.Includes bibliographical references.Genetic sequence classification is the task of assigning a known genetic label to an unknown genetic sequence. Often, this is the first step in genetic sequence analysis and is critical to understanding data produced by molecular techniques like high throughput sequencing. Here, we explore an algorithm called naive Bayes that was historically successful in classifying 16S ribosomal gene sequences for microbiome analysis. We extend the naive Bayes classifier to perform the task of general sequence classification by leveraging advancements in computational parallelism and the statistical distributions that underlie naive Bayes. In Chapter 2, we show that our implementation of naive Bayes, called WarpNL, performs within a margin of error of modern classifiers like Kraken2 and local alignment. We discuss five crucial aspects of genetic sequence classification and show how these areas affect classifier performance: the query data, the reference sequence database, the feature encoding method, the classification algorithm, and access to computational resources. In Chapter 3, we cover the critical computational advancements introduced in WarpNL that make it efficient in a modern computing framework. This includes efficient feature encoding, introduction of a log-odds ratio for comparison of naive Bayes posterior estimates, description of schema for parallel and distributed naive Bayes architectures, and use of machine learning classifiers to perform outgroup sequence classification. Finally in Chapter 4, we explore a variant of the Dirichlet multinomial distribution that underlies the naive Bayes likelihood, called the beta-Liouville multinomial. We show that the beta-Liouville multinomial can be used to enhance classifier performance, and we provide mathematical proofs regarding its convergence during maximum likelihood estimation. Overall, this work explores the naive Bayes algorithm in a modern context and shows that it is competitive for genetic sequence classification

Transform Based And Search Aware Text Compression Schemes And Compressed Domain Text Retrieval

In recent times, we have witnessed an unprecedented growth of textual information via the Internet, digital libraries and archival text in many applications. While a good fraction of this information is of transient interest, useful information of archival value will continue to accumulate. We need ways to manage, organize and transport this data from one point to the other on data communications links with limited bandwidth. We must also have means to speedily find the information we need from this huge mass of data. Sometimes, a single site may also contain large collections of data such as a library database, thereby requiring an efficient search mechanism even to search within the local data. To facilitate the information retrieval, an emerging ad hoc standard for uncompressed text is XML which preprocesses the text by putting additional user defined metadata such as DTD or hyperlinks to enable searching with better efficiency and effectiveness. This increases the file size considerably, underscoring the importance of applying text compression. On account of efficiency (in terms of both space and time), there is a need to keep the data in compressed form for as much as possible. Text compression is concerned with techniques for representing the digital text data in alternate representations that takes less space. Not only does it help conserve the storage space for archival and online data, it also helps system performance by requiring less number of secondary storage (disk or CD Rom) accesses and improves the network transmission bandwidth utilization by reducing the transmission time. Unlike static images or video, there is no international standard for text compression, although compressed formats like .zip, .gz, .Z files are increasingly being used. In general, data compression methods are classified as lossless or lossy. Lossless compression allows the original data to be recovered exactly. Although used primarily for text data, lossless compression algorithms are useful in special classes of images such as medical imaging, finger print data, astronomical images and data bases containing mostly vital numerical data, tables and text information. Many lossy algorithms use lossless methods at the final stage of the encoding stage underscoring the importance of lossless methods for both lossy and lossless compression applications. In order to be able to effectively utilize the full potential of compression techniques for the future retrieval systems, we need efficient information retrieval in the compressed domain. This means that techniques must be developed to search the compressed text without decompression or only with partial decompression independent of whether the search is done on the text or on some inversion table corresponding to a set of key words for the text. In this dissertation, we make the following contributions: (1) Star family compression algorithms: We have proposed an approach to develop a reversible transformation that can be applied to a source text that improves existing algorithm\u27s ability to compress. We use a static dictionary to convert the English words into predefined symbol sequences. These transformed sequences create additional context information that is superior to the original text. Thus we achieve some compression at the preprocessing stage. We have a series of transforms which improve the performance. Star transform requires a static dictionary for a certain size. To avoid the considerable complexity of conversion, we employ the ternary tree data structure that efficiently converts the words in the text to the words in the star dictionary in linear time. (2) Exact and approximate pattern matching in Burrows-Wheeler transformed (BWT) files: We proposed a method to extract the useful context information in linear time from the BWT transformed text. The auxiliary arrays obtained from BWT inverse transform brings logarithm search time. Meanwhile, approximate pattern matching can be performed based on the results of exact pattern matching to extract the possible candidate for the approximate pattern matching. Then fast verifying algorithm can be applied to those candidates which could be just small parts of the original text. We present algorithms for both k-mismatch and k-approximate pattern matching in BWT compressed text. A typical compression system based on BWT has Move-to-Front and Huffman coding stages after the transformation. We propose a novel approach to replace the Move-to-Front stage in order to extend compressed domain search capability all the way to the entropy coding stage. A modification to the Move-to-Front makes it possible to randomly access any part of the compressed text without referring to the part before the access point. (3) Modified LZW algorithm that allows random access and partial decoding for the compressed text retrieval: Although many compression algorithms provide good compression ratio and/or time complexity, LZW is the first one studied for the compressed pattern matching because of its simplicity and efficiency. Modifications on LZW algorithm provide the extra advantage for fast random access and partial decoding ability that is especially useful for text retrieval systems. Based on this algorithm, we can provide a dynamic hierarchical semantic structure for the text, so that the text search can be performed on the expected level of granularity. For example, user can choose to retrieve a single line, a paragraph, or a file, etc. that contains the keywords. More importantly, we will show that parallel encoding and decoding algorithm is trivial with the modified LZW. Both encoding and decoding can be performed with multiple processors easily and encoding and decoding process are independent with respect to the number of processors

De Novo Analysis of Transcriptome Dynamics in the Migratory Locust during the Development of Phase Traits

Locusts exhibit remarkable density-dependent phenotype (phase) changes from the solitary to the gregarious, making them one of the most destructive agricultural pests. This phenotype polyphenism arises from a single genome and diverse transcriptomes in different conditions. Here we report a de novo transcriptome for the migratory locust and a comprehensive, representative core gene set. We carried out assembly of 21.5 Gb Illumina reads, generated 72,977 transcripts with N50 2,275 bp and identified 11,490 locust protein-coding genes. Comparative genomics analysis with eight other sequenced insects was carried out to indentify the genomic divergence between hemimetabolous and holometabolous insects for the first time and 18 genes relevant to development was found. We further utilized the quantitative feature of RNA-seq to measure and compare gene expression among libraries. We first discovered how divergence in gene expression between two phases progresses as locusts develop and identified 242 transcripts as candidates for phase marker genes. Together with the detailed analysis of deep sequencing data of the 4th instar, we discovered a phase-dependent divergence of biological investment in the molecular level. Solitary locusts have higher activity in biosynthetic pathways while gregarious locusts show higher activity in environmental interaction, in which genes and pathways associated with regulation of neurotransmitter activities, such as neurotransmitter receptors, synthetase, transporters, and GPCR signaling pathways, are strongly involved. Our study, as the largest de novo transcriptome to date, with optimization of sequencing and assembly strategy, can further facilitate the application of de novo transcriptome. The locust transcriptome enriches genetic resources for hemimetabolous insects and our understanding of the origin of insect metamorphosis. Most importantly, we identified genes and pathways that might be involved in locust development and phase change, and may thus benefit pest management