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

GHOSTM: A GPU-Accelerated Homology Search Tool for Metagenomics

A large number of sensitive homology searches are required for mapping DNA sequence fragments to known protein sequences in public and private databases during metagenomic analysis. BLAST is currently used for this purpose, but its calculation speed is insufficient, especially for analyzing the large quantities of sequence data obtained from a next-generation sequencer. However, faster search tools, such as BLAT, do not have sufficient search sensitivity for metagenomic analysis. Thus, a sensitive and efficient homology search tool is in high demand for this type of analysis.We developed a new, highly efficient homology search algorithm suitable for graphics processing unit (GPU) calculations that was implemented as a GPU system that we called GHOSTM. The system first searches for candidate alignment positions for a sequence from the database using pre-calculated indexes and then calculates local alignments around the candidate positions before calculating alignment scores. We implemented both of these processes on GPUs. The system achieved calculation speeds that were 130 and 407 times faster than BLAST with 1 GPU and 4 GPUs, respectively. The system also showed higher search sensitivity and had a calculation speed that was 4 and 15 times faster than BLAT with 1 GPU and 4 GPUs.We developed a GPU-optimized algorithm to perform sensitive sequence homology searches and implemented the system as GHOSTM. Currently, sequencing technology continues to improve, and sequencers are increasingly producing larger and larger quantities of data. This explosion of sequence data makes computational analysis with contemporary tools more difficult. We developed GHOSTM, which is a cost-efficient tool, and offer this tool as a potential solution to this problem

SaLoBa: Maximizing Data Locality and Workload Balance for Fast Sequence Alignment on GPUs

Sequence alignment forms an important backbone in many sequencing applications. A commonly used strategy for sequence alignment is an approximate string matching with a two-dimensional dynamic programming approach. Although some prior work has been conducted on GPU acceleration of a sequence alignment, we identify several shortcomings that limit exploiting the full computational capability of modern GPUs. This paper presents SaLoBa, a GPU-accelerated sequence alignment library focused on seed extension. Based on the analysis of previous work with real-world sequencing data, we propose techniques to exploit the data locality and improve workload balancing. The experimental results reveal that SaLoBa significantly improves the seed extension kernel compared to state-of-the-art GPU-based methods.Comment: Published at IPDPS'2

Genome sequence alignment in processing-In-memory architectures

Finalmente, también realizamos un estudio experimental de varias arquitecturas con diferentes tecnologías de memoria (DDR y HBM) y núcleos de procesamiento de distintos tipos, explotando, en algunos casos, procesamiento en la memoria (PIM). La aplicación de referencia es Bowtie2, una aplicación completa para el alineamiento de secuencias en el genoma. La implementación y evaluación de estas arquitecturas se realiza utilizando un simulador arquitectural basado en gem5.La combinación de la aparición de un cuello de botella en el acceso a los datos y la creciente importancia de las aplicaciones de procesamiento intensivo de datos, muy limitadas por el sistema de memoria, crea un importante problema que debe ser abordado. Por ello, en esta tesis nos proponemos afrontar este problema e intentar reducir su efecto en la medida de lo posible. El principal objetivo de esta tesis es el diseño de nuevas soluciones arquitecturales y algorítmicas para superar el problema del cuello de botella conocido como memory-wall y mejorar el rendimiento de aplicaciones con gran uso de memoria que no son capaces de beneficiarse lo suficiente de las jerarquías de memoria actuales. Además, creemos que es esencial centrarse en la eficiencia energética, un factor cuya importancia crece cada día y uno de los factores más limitantes en la computación de alto rendimiento. Las principales contribuciones de esta tesis son: Primero, analizamos el comportamiento de aplicaciones con accesos de memoria aleatorios, que no aprovechan correctamente las nuevas arquitecturas de memoria con jerarquías cache profundas. Específicamente, analizamos la estructura de datos FM-index y un algoritmo de búsqueda de secuencias basado en esa estructura, ampliamente usado en el alineamiento de secuencias en el genoma. Después de este análisis y de obtener un conocimiento más detallado del cuello de botella de la memoria, proponemos una nueva versión de FM-index que permite reducir el consumo de ancho de banda de memoria, de forma que mejora significativamente el rendimiento computacional. Posteriormente, proponemos una nueva arquitectura energéticamente eficiente, basada en un cubo de memoria en 3D (3D-Stacked) al que añadimos unos núcleos sencillos de bajo consumo en su capa lógica. Esta arquitectura permite la ejecución cerca de los datos (near-data-processing

Computing Platforms for Big Biological Data Analytics: Perspectives and Challenges.

The last decade has witnessed an explosion in the amount of available biological sequence data, due to the rapid progress of high-throughput sequencing projects. However, the biological data amount is becoming so great that traditional data analysis platforms and methods can no longer meet the need to rapidly perform data analysis tasks in life sciences. As a result, both biologists and computer scientists are facing the challenge of gaining a profound insight into the deepest biological functions from big biological data. This in turn requires massive computational resources. Therefore, high performance computing (HPC) platforms are highly needed as well as efficient and scalable algorithms that can take advantage of these platforms. In this paper, we survey the state-of-the-art HPC platforms for big biological data analytics. We first list the characteristics of big biological data and popular computing platforms. Then we provide a taxonomy of different biological data analysis applications and a survey of the way they have been mapped onto various computing platforms. After that, we present a case study to compare the efficiency of different computing platforms for handling the classical biological sequence alignment problem. At last we discuss the open issues in big biological data analytics