A dynamic programming model to solve optimisation problems using GPUs

This thesis presents a parallel, dynamic programming based model which is deployed on the GPU of a system to accelerate the solving of optimisation problems. This is achieved by simultaneously running GPU based computations, and memory transactions, allowing computation to never pause, and overcoming the memory constraints of solving large problem instances. Due to this some optimisation problems, which are currently not solved in an exact manner for real world sized instances due to their complexity, are moved into the solvable realm. The model is implemented to solve, a range of different test problems, where artificially constructed test data is used to ensure good performance even in the worst cases. Through this extensive testing, we can be confident the model will perform well when used to solve real world test cases. Testing of the model was carried out using a range of different implementation parameters in relation to deployment on the GPU, in order to identify both optimal implementation parameters, and how the model will operate when running on different systems. All problems, when implemented in parallel using the model, show run-time improvements compared to the sequential implementations, in some instances up to hundreds of times faster, but more importantly also show high efficiency metrics for the utilisation of GPU resources. Throughout testing emphasis has been placed on GPU based metrics to ensure the wider generic applicability of the model. Finally, the parallel model allows for new problems to be defined through the use of a simple file format, enabling wider usage of the model

Techniques of design optimisation for algorithms implemented in software

The overarching objective of this thesis was to develop tools for parallelising, optimising, and implementing algorithms on parallel architectures, in particular General Purpose Graphics Processors (GPGPUs). Two projects were chosen from different application areas in which GPGPUs are used: a defence application involving image compression, and a modelling application in bioinformatics (computational immunology). Each project had its own specific objectives, as well as supporting the overall research goal. The defence / image compression project was carried out in collaboration with the Jet Propulsion Laboratories. The specific questions were: to what extent an algorithm designed for bit-serial for the lossless compression of hyperspectral images on-board unmanned vehicles (UAVs) in hardware could be parallelised, whether GPGPUs could be used to implement that algorithm, and whether a software implementation with or without GPGPU acceleration could match the throughput of a dedicated hardware (FPGA) implementation. The dependencies within the algorithm were analysed, and the algorithm parallelised. The algorithm was implemented in software for GPGPU, and optimised. During the optimisation process, profiling revealed less than optimal device utilisation, but no further optimisations resulted in an improvement in speed. The design had hit a local-maximum of performance. Analysis of the arithmetic intensity and data-flow exposed flaws in the standard optimisation metric of kernel occupancy used for GPU optimisation. Redesigning the implementation with revised criteria (fused kernels, lower occupancy, and greater data locality) led to a new implementation with 10x higher throughput. GPGPUs were shown to be viable for on-board implementation of the CCSDS lossless hyperspectral image compression algorithm, exceeding the performance of the hardware reference implementation, and providing sufficient throughput for the next generation of image sensor as well. The second project was carried out in collaboration with biologists at the University of Arizona and involved modelling a complex biological system – VDJ recombination involved in the formation of T-cell receptors (TCRs). Generation of immune receptors (T cell receptor and antibodies) by VDJ recombination is an enormously complex process, which can theoretically synthesize greater than 1018 variants. Originally thought to be a random process, the underlying mechanisms clearly have a non-random nature that preferentially creates a small subset of immune receptors in many individuals. Understanding this bias is a longstanding problem in the field of immunology. Modelling the process of VDJ recombination to determine the number of ways each immune receptor can be synthesized, previously thought to be untenable, is a key first step in determining how this special population is made. The computational tools developed in this thesis have allowed immunologists for the first time to comprehensively test and invalidate a longstanding theory (convergent recombination) for how this special population is created, while generating the data needed to develop novel hypothesis

On the role of metaheuristic optimization in bioinformatics

Metaheuristic algorithms are employed to solve complex and large-scale optimization problems in many different fields, from transportation and smart cities to finance. This paper discusses how metaheuristic algorithms are being applied to solve different optimization problems in the area of bioinformatics. While the text provides references to many optimization problems in the area, it focuses on those that have attracted more interest from the optimization community. Among the problems analyzed, the paper discusses in more detail the molecular docking problem, the protein structure prediction, phylogenetic inference, and different string problems. In addition, references to other relevant optimization problems are also given, including those related to medical imaging or gene selection for classification. From the previous analysis, the paper generates insights on research opportunities for the Operations Research and Computer Science communities in the field of bioinformatics

Parallelization of dynamic programming recurrences in computational biology

The rapid growth of biosequence databases over the last decade has led to a performance bottleneck in the applications analyzing them. In particular, over the last five years DNA sequencing capacity of next-generation sequencers has been doubling every six months as costs have plummeted. The data produced by these sequencers is overwhelming traditional compute systems. We believe that in the future compute performance, not sequencing, will become the bottleneck in advancing genome science. In this work, we investigate novel computing platforms to accelerate dynamic programming algorithms, which are popular in bioinformatics workloads. We study algorithm-specific hardware architectures that exploit fine-grained parallelism in dynamic programming kernels using field-programmable gate arrays: FPGAs). We advocate a high-level synthesis approach, using the recurrence equation abstraction to represent dynamic programming and polyhedral analysis to exploit parallelism. We suggest a novel technique within the polyhedral model to optimize for throughput by pipelining independent computations on an array. This design technique improves on the state of the art, which builds latency-optimal arrays. We also suggest a method to dynamically switch between a family of designs using FPGA reconfiguration to achieve a significant performance boost. We have used polyhedral methods to parallelize the Nussinov RNA folding algorithm to build a family of accelerators that can trade resources for parallelism and are between 15-130x faster than a modern dual core CPU implementation. A Zuker RNA folding accelerator we built on a single workstation with four Xilinx Virtex 4 FPGAs outperforms 198 3 GHz Intel Core 2 Duo processors. Furthermore, our design running on a single FPGA is an order of magnitude faster than competing implementations on similar-generation FPGAs and graphics processors. Our work is a step toward the goal of automated synthesis of hardware accelerators for dynamic programming algorithms

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

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

MR-CUDASW - GPU accelerated Smith-Waterman algorithm for medium-length (meta)genomic data

The idea of using a graphics processing unit (GPU) for more than simply graphic output purposes has been around for quite some time in scientific communities. However, it is only recently that its benefits for a range of bioinformatics and life sciences compute-intensive tasks has been recognized. This thesis investigates the possibility of improving the performance of the overlap determination stage of an Overlap Layout Consensus (OLC)-based assembler by using a GPU-based implementation of the Smith-Waterman algorithm. In this thesis an existing GPU-accelerated sequence alignment algorithm is adapted and expanded to reduce its completion time. A number of improvements and changes are made to the original software. Workload distribution, query profile construction, and thread scheduling techniques implemented by the original program are replaced by custom methods specifically designed to handle medium-length reads. Accordingly, this algorithm is the first highly parallel solution that has been specifically optimized to process medium-length nucleotide reads (DNA/RNA) from modern sequencing machines (i.e. Ion Torrent). Results show that the software reaches up to 82 GCUPS (Giga Cell Updates Per Second) on a single-GPU graphic card running on a commodity desktop hardware. As a result it is the fastest GPU-based implemen- tation of the Smith-Waterman algorithm tailored for processing medium-length nucleotide reads. Despite being designed for performing the Smith-Waterman algorithm on medium-length nucleotide sequences, this program also presents great potential for improving heterogeneous computing with CUDA-enabled GPUs in general and is expected to make contributions to other research problems that require sensitive pairwise alignment to be applied to a large number of reads. Our results show that it is possible to improve the performance of bioinformatics algorithms by taking full advantage of the compute resources of the underlying commodity hardware and further, these results are especially encouraging since GPU performance grows faster than multi-core CPUs

Accelerated Profile HMM Searches

Profile hidden Markov models (profile HMMs) and probabilistic inference methods have made important contributions to the theory of sequence database homology search. However, practical use of profile HMM methods has been hindered by the computational expense of existing software implementations. Here I describe an acceleration heuristic for profile HMMs, the “multiple segment Viterbi” (MSV) algorithm. The MSV algorithm computes an optimal sum of multiple ungapped local alignment segments using a striped vector-parallel approach previously described for fast Smith/Waterman alignment. MSV scores follow the same statistical distribution as gapped optimal local alignment scores, allowing rapid evaluation of significance of an MSV score and thus facilitating its use as a heuristic filter. I also describe a 20-fold acceleration of the standard profile HMM Forward/Backward algorithms using a method I call “sparse rescaling”. These methods are assembled in a pipeline in which high-scoring MSV hits are passed on for reanalysis with the full HMM Forward/Backward algorithm. This accelerated pipeline is implemented in the freely available HMMER3 software package. Performance benchmarks show that the use of the heuristic MSV filter sacrifices negligible sensitivity compared to unaccelerated profile HMM searches. HMMER3 is substantially more sensitive and 100- to 1000-fold faster than HMMER2. HMMER3 is now about as fast as BLAST for protein searches

Implementing and Accelerating HMMER3 Protein Sequence Search on CUDA-Enabled GPU

The recent emergence of multi-core CPU and many-core GPU architectures has made parallel computing more accessible. Hundreds of industrial and research applications have been mapped onto GPUs to further utilize the extra computing resource. In bioinformatics, HMMER is a set of widely used applications for sequence analysis based on Hidden Markov Model. One of the tools in HMMER, hmmsearch, and the Smith-Waterman algorithm are two important tools for protein sequence analysis that use dynamic programming. Both tools are particularly well-suited for many-core GPU architecture due to the parallel nature of sequence database searches. After studying the existing research on CUDA acceleration in bioinformatics, this thesis investigated the acceleration of the key Multiple Segment Viterbi algorithm in HMMER version 3. A fully-featured CUDA-enabled protein database search tool cudaHmmsearch was designed, implemented and optimized. We demonstrated a variety of optimization strategies that are useful for general purpose GPU-based applications. Based on our optimization experience in parallel computing, six steps were summarized for optimizing performance using CUDA programming. We made comprehensive tests and analysis for multiple enhancements in our GPU kernels in order to demonstrate the effectiveness of selected approaches. The performance analysis showed that GPUs are able to deal with intensive computations, but are very sensitive to random accesses to the global memory. The results show that our implementation achieved 2.5x speedup over the single-threaded HMMER3 CPU SSE2 implementation on average

Computational Tools for Immune Repertoire Characterization and Primer Set Design

The enormous decrease in the cost of genomic sequencing over the past two decades has enabled researchers to revisit previously unaddressable questions in sequence analysis. However, this boom of genomic information has introduced new sets of problems that often demand computationally efficient methods. In this work, we describe computational tools for two such settings involving large-scale genomic data: 1) estimating copy number and allelic variation in two highly complex gene families, and 2) selective sequencing of a target genome in a complex DNA sample.We first describe a method that takes short reads from high-throughput sequencing and characterizes both copy number and allelic variation in the IGHV and TRBV loci. These two loci can vary extensively between individuals in copy number and contain genes that are highly similar, making their analysis technically challenging. Additionally, we have conducted the first study of a globally diverse sample of hundreds of individuals in these two loci from over a hundred populations. In addition to providing insight into the different evolutionary paths of the IGHV and TRBV loci, our results are also important to the adaptive immune repertoire sequencing community, where the lack of frequencies of common alleles and copy number variants is hampering existing analytical pipelines.In our second problem setting, we describe SOAPswga, an optimized and parallelized pipeline for primer design in the context of selective amplification. Unlike previous heuristic-based methods, SOAPswga uses machine learning methods to evaluate both individual primers and primer sets. Additionally, rather than brute force search for primer sets, such as in predecessor methods, SOAPswga uses branch-and-bound principles to pursue only the most promising sets. These optimizations, including the parallelization of each step, allow for a huge decrease in runtime from the order of weeks to minutes. We also discuss the results of our pipeline applied to the selective amplification of Mycobacterium tuberculosis in a sample of human blood. Lastly, we expand on the importance of this work, and in general, its potential usefulness to any setting consisting of targeted sequencing