High Performance Computing for DNA Sequence Alignment and Assembly

Recent advances in DNA sequencing technology have dramatically increased the scale and scope of DNA sequencing. These data are used for a wide variety of important biological analyzes, including genome sequencing, comparative genomics, transcriptome analysis, and personalized medicine but are complicated by the volume and complexity of the data involved. Given the massive size of these datasets, computational biology must draw on the advances of high performance computing. Two fundamental computations in computational biology are read alignment and genome assembly. Read alignment maps short DNA sequences to a reference genome to discover conserved and polymorphic regions of the genome. Genome assembly computes the sequence of a genome from many short DNA sequences. Both computations benefit from recent advances in high performance computing to efficiently process the huge datasets involved, including using highly parallel graphics processing units (GPUs) as high performance desktop processors, and using the MapReduce framework coupled with cloud computing to parallelize computation to large compute grids. This dissertation demonstrates how these technologies can be used to accelerate these computations by orders of magnitude, and have the potential to make otherwise infeasible computations practical

Novel computational techniques for mapping and classifying Next-Generation Sequencing data

Since their emergence around 2006, Next-Generation Sequencing technologies have been revolutionizing biological and medical research. Quickly obtaining an extensive amount of short or long reads of DNA sequence from almost any biological sample enables detecting genomic variants, revealing the composition of species in a metagenome, deciphering cancer biology, decoding the evolution of living or extinct species, or understanding human migration patterns and human history in general. The pace at which the throughput of sequencing technologies is increasing surpasses the growth of storage and computer capacities, which creates new computational challenges in NGS data processing. In this thesis, we present novel computational techniques for read mapping and taxonomic classification. With more than a hundred of published mappers, read mapping might be considered fully solved. However, the vast majority of mappers follow the same paradigm and only little attention has been paid to non-standard mapping approaches. Here, we propound the so-called dynamic mapping that we show to significantly improve the resulting alignments compared to traditional mapping approaches. Dynamic mapping is based on exploiting the information from previously computed alignments, helping to improve the mapping of subsequent reads. We provide the first comprehensive overview of this method and demonstrate its qualities using Dynamic Mapping Simulator, a pipeline that compares various dynamic mapping scenarios to static mapping and iterative referencing. An important component of a dynamic mapper is an online consensus caller, i.e., a program collecting alignment statistics and guiding updates of the reference in the online fashion. We provide Ococo, the first online consensus caller that implements a smart statistics for individual genomic positions using compact bit counters. Beyond its application to dynamic mapping, Ococo can be employed as an online SNP caller in various analysis pipelines, enabling SNP calling from a stream without saving the alignments on disk. Metagenomic classification of NGS reads is another major topic studied in the thesis. Having a database with thousands of reference genomes placed on a taxonomic tree, the task is to rapidly assign a huge amount of NGS reads to tree nodes, and possibly estimate the relative abundance of involved species. In this thesis, we propose improved computational techniques for this task. In a series of experiments, we show that spaced seeds consistently improve the classification accuracy. We provide Seed-Kraken, a spaced seed extension of Kraken, the most popular classifier at present. Furthermore, we suggest ProPhyle, a new indexing strategy based on a BWT-index, obtaining a much smaller and more informative index compared to Kraken. We provide a modified version of BWA that improves the BWT-index for a quick k-mer look-up

Phylogeny-Aware Placement and Alignment Methods for Short Reads

In recent years bioinformatics has entered a new phase: New sequencing methods, generally referred to as Next Generation Sequencing (NGS) have become widely available. This thesis introduces algorithms for phylogeny aware analysis of short sequence reads, as generated by NGS methods in the context of metagenomic studies. A considerable part of this work focuses on the technical (w.r.t. performance) challenges of these new algorithms, which have been developed specifically to exploit parallelism

Multiple Biolgical Sequence Alignment: Scoring Functions, Algorithms, and Evaluations

Aligning multiple biological sequences such as protein sequences or DNA/RNA sequences is a fundamental task in bioinformatics and sequence analysis. These alignments may contain invaluable information that scientists need to predict the sequences\u27 structures, determine the evolutionary relationships between them, or discover drug-like compounds that can bind to the sequences. Unfortunately, multiple sequence alignment (MSA) is NP-Complete. In addition, the lack of a reliable scoring method makes it very hard to align the sequences reliably and to evaluate the alignment outcomes. In this dissertation, we have designed a new scoring method for use in multiple sequence alignment. Our scoring method encapsulates stereo-chemical properties of sequence residues and their substitution probabilities into a tree-structure scoring scheme. This new technique provides a reliable scoring scheme with low computational complexity. In addition to the new scoring scheme, we have designed an overlapping sequence clustering algorithm to use in our new three multiple sequence alignment algorithms. One of our alignment algorithms uses a dynamic weighted guidance tree to perform multiple sequence alignment in progressive fashion. The use of dynamic weighted tree allows errors in the early alignment stages to be corrected in the subsequence stages. Other two algorithms utilize sequence knowledge-bases and sequence consistency to produce biological meaningful sequence alignments. To improve the speed of the multiple sequence alignment, we have developed a parallel algorithm that can be deployed on reconfigurable computer models. Analytically, our parallel algorithm is the fastest progressive multiple sequence alignment algorithm

Lock-free Parallel Dynamic Programming

We show a method for parallelizing top down dynamic programs in a straightforward way by a careful choice of a lock-free shared hash table implementation and randomization of the order in which the dynamic program computes its subproblems. This generic approach is applied to dynamic programs for knapsack, shortest paths, and RNA structure alignment, as well as to a state-of-the-art solution for minimizing the máximum number of open stacks. Experimental results are provided on three different modern multicore architectures which show that this parallelization is effective and reasonably scalable. In particular, we obtain over 10 times speedup for 32 threads on the open stacks problem

EMPIRICAL TRANSITION PROBABILITY INDEXING GENOME SEQUENCE ALIGNMENT BASED ON CUDA

After Deoxyribonucleic Acid (DNA) was discovered, finding the similarities in proteins became a fundamental procedure. In recent years, there has been a rapid development in alignment technologies. Alignment is the basic operation used to compare biological sequences and to determine the similarities that eventually result for structural, functional, or biological process relationships. These new technologies produce data in the order of numerous gigabyte-pairs per day. With the use of a Graphics Processing Unit (GPU), these data can be solved. We can utilize a GPU in computation as a massive parallel processor because the GPU consists of multiple pips. This new hardware creates new opportunities to study and improve current algorithms that are used for research in DNA alignment. In this thesis, we proposed a new algorithm to tackle this problem. We matched blocks of reference and target sequences based on the similarities between their empirical transition probabilities matrixes. The computations were conducted on an NVIDIA GTX 760, equipped with 2GB RAM, running Microsoft Windows 8.1 Professional. Our experimental results show robustness in nucleotide sequence alignment, and the parallelized transition probability indexing on a GPU achieves faster results than a former study of a proposed sequential method on a CPU

Bioinformatics

This book is divided into different research areas relevant in Bioinformatics such as biological networks, next generation sequencing, high performance computing, molecular modeling, structural bioinformatics, molecular modeling and intelligent data analysis. Each book section introduces the basic concepts and then explains its application to problems of great relevance, so both novice and expert readers can benefit from the information and research works presented here