High performance bioinformatics and computational biology on general-purpose graphics processing units

Bioinformatics and Computational Biology (BCB) is a relatively new multidisciplinary field which brings together many aspects of the fields of biology, computer science, statistics, and engineering. Bioinformatics extracts useful information from biological data and makes these more intuitive and understandable by applying principles of information sciences, while computational biology harnesses computational approaches and technologies to answer biological questions conveniently. Recent years have seen an explosion of the size of biological data at a rate which outpaces the rate of increases in the computational power of mainstream computer technologies, namely general purpose processors (GPPs). The aim of this thesis is to explore the use of off-the-shelf Graphics Processing Unit (GPU) technology in the high performance and efficient implementation of BCB applications in order to meet the demands of biological data increases at affordable cost. The thesis presents detailed design and implementations of GPU solutions for a number of BCB algorithms in two widely used BCB applications, namely biological sequence alignment and phylogenetic analysis. Biological sequence alignment can be used to determine the potential information about a newly discovered biological sequence from other well-known sequences through similarity comparison. On the other hand, phylogenetic analysis is concerned with the investigation of the evolution and relationships among organisms, and has many uses in the fields of system biology and comparative genomics. In molecular-based phylogenetic analysis, the relationship between species is estimated by inferring the common history of their genes and then phylogenetic trees are constructed to illustrate evolutionary relationships among genes and organisms. However, both biological sequence alignment and phylogenetic analysis are computationally expensive applications as their computing and memory requirements grow polynomially or even worse with the size of sequence databases. The thesis firstly presents a multi-threaded parallel design of the Smith- Waterman (SW) algorithm alongside an implementation on NVIDIA GPUs. A novel technique is put forward to solve the restriction on the length of the query sequence in previous GPU-based implementations of the SW algorithm. Based on this implementation, the difference between two main task parallelization approaches (Inter-task and Intra-task parallelization) is presented. The resulting GPU implementation matches the speed of existing GPU implementations while providing more flexibility, i.e. flexible length of sequences in real world applications. It also outperforms an equivalent GPPbased implementation by 15x-20x. After this, the thesis presents the first reported multi-threaded design and GPU implementation of the Gapped BLAST with Two-Hit method algorithm, which is widely used for aligning biological sequences heuristically. This achieved up to 3x speed-up improvements compared to the most optimised GPP implementations. The thesis then presents a multi-threaded design and GPU implementation of a Neighbor-Joining (NJ)-based method for phylogenetic tree construction and multiple sequence alignment (MSA). This achieves 8x-20x speed up compared to an equivalent GPP implementation based on the widely used ClustalW software. The NJ method however only gives one possible tree which strongly depends on the evolutionary model used. A more advanced method uses maximum likelihood (ML) for scoring phylogenies with Markov Chain Monte Carlo (MCMC)-based Bayesian inference. The latter was the subject of another multi-threaded design and GPU implementation presented in this thesis, which achieved 4x-8x speed up compared to an equivalent GPP implementation based on the widely used MrBayes software. Finally, the thesis presents a general evaluation of the designs and implementations achieved in this work as a step towards the evaluation of GPU technology in BCB computing, in the context of other computer technologies including GPPs and Field Programmable Gate Arrays (FPGA) technology

SWAPHI: Smith-Waterman Protein Database Search on Xeon Phi Coprocessors

The maximal sensitivity of the Smith-Waterman (SW) algorithm has enabled its wide use in biological sequence database search. Unfortunately, the high sensitivity comes at the expense of quadratic time complexity, which makes the algorithm computationally demanding for big databases. In this paper, we present SWAPHI, the first parallelized algorithm employing Xeon Phi coprocessors to accelerate SW protein database search. SWAPHI is designed based on the scale-and-vectorize approach, i.e. it boosts alignment speed by effectively utilizing both the coarse-grained parallelism from the many co-processing cores (scale) and the fine-grained parallelism from the 512-bit wide single instruction, multiple data (SIMD) vectors within each core (vectorize). By searching against the large UniProtKB/TrEMBL protein database, SWAPHI achieves a performance of up to 58.8 billion cell updates per second (GCUPS) on one coprocessor and up to 228.4 GCUPS on four coprocessors. Furthermore, it demonstrates good parallel scalability on varying number of coprocessors, and is also superior to both SWIPE on 16 high-end CPU cores and BLAST+ on 8 cores when using four coprocessors, with the maximum speedup of 1.52 and 1.86, respectively. SWAPHI is written in C++ language (with a set of SIMD intrinsics), and is freely available at http://swaphi.sourceforge.net.Comment: A short version of this paper has been accepted by the IEEE ASAP 2014 conferenc

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

CUDA compatible GPU cards as efficient hardware accelerators for Smith-Waterman sequence alignment

Background Searching for similarities in protein and DNA databases has become a routine procedure in Molecular Biology. The Smith-Waterman algorithm has been available for more than 25 years. It is based on a dynamic programming approach that explores all the possible alignments between two sequences; as a result it returns the optimal local alignment. Unfortunately, the computational cost is very high, requiring a number of operations proportional to the product of the length of two sequences. Furthermore, the exponential growth of protein and DNA databases makes the Smith-Waterman algorithm unrealistic for searching similarities in large sets of sequences. For these reasons heuristic approaches such as those implemented in FASTA and BLAST tend to be preferred, allowing faster execution times at the cost of reduced sensitivity. The main motivation of our work is to exploit the huge computational power of commonly available graphic cards, to develop high performance solutions for sequence alignment. Results In this paper we present what we believe is the fastest solution of the exact Smith-Waterman algorithm running on commodity hardware. It is implemented in the recently released CUDA programming environment by NVidia. CUDA allows direct access to the hardware primitives of the last-generation Graphics Processing Units (GPU) G80. Speeds of more than 3.5 GCUPS (Giga Cell Updates Per Second) are achieved on a workstation running two GeForce 8800 GTX. Exhaustive tests have been done to compare our implementation to SSEARCH and BLAST, running on a 3 GHz Intel Pentium IV processor. Our solution was also compared to a recently published GPU implementation and to a Single Instruction Multiple Data (SIMD) solution. These tests show that our implementation performs from 2 to 30 times faster than any other previous attempt available on commodity hardware. Conclusions The results show that graphic cards are now sufficiently advanced to be used as efficient hardware accelerators for sequence alignment. Their performance is better than any alternative available on commodity hardware platforms. The solution presented in this paper allows large scale alignments to be performed at low cost, using the exact Smith-Waterman algorithm instead of the largely adopted heuristic approaches

Inexact Mapping of Short Biological Sequences in High Performance Computational Environments

La bioinformática es la aplicación de las ciencias computacionales a la gestión y análisis de datos biológicos. A partir de 2005, con la aparición de los secuenciadores de ADN de nueva generación surge lo que se conoce como Next Generation Sequencing o NGS. Un único experimento biológico puesto en marcha en una máquina de secuenciación NGS puede producir fácilmente cientos de gigabytes o incluso terabytes de datos. Dependiendo de la técnica elegida este proceso puede realizarse en unas pocas horas o días. La disponibilidad de recursos locales asequibles, tales como los procesadores multinúcleo o las nuevas tarjetas gráfi cas preparadas para el cálculo de propósito general GPGPU (General Purpose Graphic Processing Unit ), constituye una gran oportunidad para hacer frente a estos problemas. En la actualidad, un tema abordado con frecuencia es el alineamiento de secuencias de ADN. En bioinformática, el alineamiento permite comparar dos o más secuencias de ADN, ARN, o estructuras primarias proteicas, resaltando sus zonas de similitud. Dichas similitudes podrían indicar relaciones funcionales o evolutivas entre los genes o proteínas consultados. Además, la existencia de similitudes entre las secuencias de un individuo paciente y de otro individuo con una enfermedad genética detectada podría utilizarse de manera efectiva en el campo de la medicina diagnóstica. El problema en torno al que gira el desarrollo de la tesis doctoral consiste en la localización de fragmentos de secuencia cortos dentro del ADN. Esto se conoce bajo el sobrenombre de mapeo de secuencia o sequence mapping. Dicho mapeo debe permitir errores, pudiendo mapear secuencias incluso existiendo variabilidad genética o errores de lectura en el mapeo. Existen diversas técnicas para abordar el mapeo, pero desde la aparición de la NGS destaca la búsqueda por pre jos indexados y agrupados mediante la transformada de Burrows-Wheeler [28] (o BWT en lo sucesivo). Dicha transformada se empleó originalmente en técnicas de compresión de datos, como es el caso del algoritmo bzip2. Su utilización como herramienta para la indización y búsqueda posterior de información es más reciente [22]. La ventaja es que su complejidad computacional depende únicamente de la longitud de la secuencia a mapear. Por otra parte, una gran cantidad de técnicas de alineamiento se basan en algoritmos de programación dinámica, ya sea Smith-Watterman o modelos ocultos de Markov. Estos proporcionan mayor sensibilidad, permitiendo mayor cantidad de errores, pero su coste computacional es mayor y depende del tamaño de la secuencia multiplicado por el de la cadena de referencia. Muchas herramientas combinan una primera fase de búsqueda con la BWT de regiones candidatas al alineamiento y una segunda fase de alineamiento local en la que se mapean cadenas con Smith-Watterman o HMM. Cuando estamos mapeando permitiendo pocos errores, una segunda fase con un algoritmo de programación dinámica resulta demasiado costosa, por lo que una búsqueda inexacta basada en BWT puede resultar más e ficiente. La principal motivación de la tesis doctoral es la implementación de un algoritmo de búsqueda inexacta basado únicamente en la BWT, adaptándolo a las arquitecturas paralelas modernas, tanto en CPU como en GPGPU. El algoritmo constituirá un método nuevo de rami cación y poda adaptado a la información genómica. Durante el periodo de estancia se estudiarán los Modelos ocultos de Markov y se realizará una implementación sobre modelos de computación funcional GTA (Aggregate o Test o Generate), así como la paralelización en memoria compartida y distribuida de dicha plataforma de programación funcional.Salavert Torres, J. (2014). Inexact Mapping of Short Biological Sequences in High Performance Computational Environments [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/43721TESI

FPGA acceleration of sequence analysis tools in bioinformatics

Thesis (Ph.D.)--Boston UniversityWith advances in biotechnology and computing power, biological data are being produced at an exceptional rate. The purpose of this study is to analyze the application of FPGAs to accelerate high impact production biosequence analysis tools. Compared with other alternatives, FPGAs offer huge compute power, lower power consumption, and reasonable flexibility. BLAST has become the de facto standard in bioinformatic approximate string matching and so its acceleration is of fundamental importance. It is a complex highly-optimized system, consisting of tens of thousands of lines of code and a large number of heuristics. Our idea is to emulate the main phases of its algorithm on FPGA. Utilizing our FPGA engine, we quickly reduce the size of the database to a small fraction, and then use the original code to process the query. Using a standard FPGA-based system, we achieved 12x speedup over a highly optimized multithread reference code. Multiple Sequence Alignment (MSA)--the extension of pairwise Sequence Alignment to multiple Sequences--is critical to solve many biological problems. Previous attempts to accelerate Clustal-W, the most commonly used MSA code, have directly mapped a portion of the code to the FPGA. We use a new approach: we apply prefiltering of the kind commonly used in BLAST to perform the initial all-pairs alignments. This results in a speedup of from 8Ox to 190x over the CPU code (8 cores). The quality is comparable to the original according to a commonly used benchmark suite evaluated with respect to multiple distance metrics. The challenge in FPGA-based acceleration is finding a suitable application mapping. Unfortunately many software heuristics do not fall into this category and so other methods must be applied. One is restructuring: an entirely new algorithm is applied. Another is to analyze application utilization and develop accuracy/performance tradeoffs. Using our prefiltering approach and novel FPGA programming models we have achieved significant speedup over reference programs. We have applied approximation, seeding, and filtering to this end. The bulk of this study is to introduce the pros and cons of these acceleration models for biosequence analysis tools

CUDASW++: optimizing Smith-Waterman sequence database searches for CUDA-enabled graphics processing units

<p>Abstract</p> <p>Background</p> <p>The Smith-Waterman algorithm is one of the most widely used tools for searching biological sequence databases due to its high sensitivity. Unfortunately, the Smith-Waterman algorithm is computationally demanding, which is further compounded by the exponential growth of sequence databases. The recent emergence of many-core architectures, and their associated programming interfaces, provides an opportunity to accelerate sequence database searches using commonly available and inexpensive hardware.</p> <p>Findings</p> <p>Our CUDASW++ implementation (benchmarked on a single-GPU NVIDIA GeForce GTX 280 graphics card and a dual-GPU GeForce GTX 295 graphics card) provides a significant performance improvement compared to other publicly available implementations, such as SWPS3, CBESW, SW-CUDA, and NCBI-BLAST. CUDASW++ supports query sequences of length up to 59K and for query sequences ranging in length from 144 to 5,478 in Swiss-Prot release 56.6, the single-GPU version achieves an average performance of 9.509 GCUPS with a lowest performance of 9.039 GCUPS and a highest performance of 9.660 GCUPS, and the dual-GPU version achieves an average performance of 14.484 GCUPS with a lowest performance of 10.660 GCUPS and a highest performance of 16.087 GCUPS.</p> <p>Conclusion</p> <p>CUDASW++ is publicly available open-source software. It provides a significant performance improvement for Smith-Waterman-based protein sequence database searches by fully exploiting the compute capability of commonly used CUDA-enabled low-cost GPUs.</p