74 research outputs found

    Acceleration of Profile-HMM Search for Protein Sequences in Reconfigurable Hardware - Master\u27s Thesis, May 2006

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    Profile Hidden Markov models are highly expressive representations of functional units, or motifs, conserved across protein sequences. Profile-HMM search is a powerful computational technique that is used to annotate new sequences by identifying occurrences of known motifs in them. With the exponential growth of protein databases, there is an increasing demand for acceleration of such techniques. We describe an accelerator for the Viterbi algorithm using a two-stage pipelined design in which the first stage is implemented in parallel reconfigurable hardware for greater speedup. To this end, we identify algorithmic modifications that expose a high level of parallelism and characterize their impact on the accuracy and performance relative to a standard software implementation. We develop a performance model to evaluate any accelerator design and propose two alternative architectures that recover the accuracy lost by a basic architecture. We compare the performance of the two architectures to show that speedups of up to 3 orders of magnitude may be achieved. We also investigate the use of the Forward algorithm in the first pipeline stage of the accelerator using floating-point arithmetic and report its accuracy and performance

    A protein sequence analysis hardware accelerator based on divergences

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    The Viterbi algorithm is one of the most used dynamic programming algorithms for protein comparison and identification, based on hidden markov Models (HMMs). Most of the works in the literature focus on the implementation of hardware accelerators that act as a prefilter stage in the comparison process. This stage discards poorly aligned sequences with a low similarity score and forwards sequences with good similarity scores to software, where they are reprocessed to generate the sequence alignment. In order to reduce the software reprocessing time, this work proposes a hardware accelerator for the Viterbi algorithm which includes the concept of divergence, in which the region of interest of the dynamic programming matrices is delimited. We obtained gains of up to 182x when compared to unaccelerated software. The performance measurement methodology adopted in this work takes into account not only the acceleration achieved by the hardware but also the reprocessing software stage required to generate the alignment

    High performance reconfigurable architectures for biological sequence alignment

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    Bioinformatics and computational biology (BCB) is a rapidly developing multidisciplinary field which encompasses a wide range of domains, including genomic sequence alignments. It is a fundamental tool in molecular biology in searching for homology between sequences. Sequence alignments are currently gaining close attention due to their great impact on the quality aspects of life such as facilitating early disease diagnosis, identifying the characteristics of a newly discovered sequence, and drug engineering. With the vast growth of genomic data, searching for a sequence homology over huge databases (often measured in gigabytes) is unable to produce results within a realistic time, hence the need for acceleration. Since the exponential increase of biological databases as a result of the human genome project (HGP), supercomputers and other parallel architectures such as the special purpose Very Large Scale Integration (VLSI) chip, Graphic Processing Unit (GPUs) and Field Programmable Gate Arrays (FPGAs) have become popular acceleration platforms. Nevertheless, there are always trade-off between area, speed, power, cost, development time and reusability when selecting an acceleration platform. FPGAs generally offer more flexibility, higher performance and lower overheads. However, they suffer from a relatively low level programming model as compared with off-the-shelf microprocessors such as standard microprocessors and GPUs. Due to the aforementioned limitations, the need has arisen for optimized FPGA core implementations which are crucial for this technology to become viable in high performance computing (HPC). This research proposes the use of state-of-the-art reprogrammable system-on-chip technology on FPGAs to accelerate three widely-used sequence alignment algorithms; the Smith-Waterman with affine gap penalty algorithm, the profile hidden Markov model (HMM) algorithm and the Basic Local Alignment Search Tool (BLAST) algorithm. The three novel aspects of this research are firstly that the algorithms are designed and implemented in hardware, with each core achieving the highest performance compared to the state-of-the-art. Secondly, an efficient scheduling strategy based on the double buffering technique is adopted into the hardware architectures. Here, when the alignment matrix computation task is overlapped with the PE configuration in a folded systolic array, the overall throughput of the core is significantly increased. This is due to the bound PE configuration time and the parallel PE configuration approach irrespective of the number of PEs in a systolic array. In addition, the use of only two configuration elements in the PE optimizes hardware resources and enables the scalability of PE systolic arrays without relying on restricted onboard memory resources. Finally, a new performance metric is devised, which facilitates the effective comparison of design performance between different FPGA devices and families. The normalized performance indicator (speed-up per area per process technology) takes out advantages of the area and lithography technology of any FPGA resulting in fairer comparisons. The cores have been designed using Verilog HDL and prototyped on the Alpha Data ADM-XRC-5LX card with the Virtex-5 XC5VLX110-3FF1153 FPGA. The implementation results show that the proposed architectures achieved giga cell updates per second (GCUPS) performances of 26.8, 29.5 and 24.2 respectively for the acceleration of the Smith-Waterman with affine gap penalty algorithm, the profile HMM algorithm and the BLAST algorithm. In terms of speed-up improvements, comparisons were made on performance of the designed cores against their corresponding software and the reported FPGA implementations. In the case of comparison with equivalent software execution, acceleration of the optimal alignment algorithm in hardware yielded an average speed-up of 269x as compared to the SSEARCH 35 software. For the profile HMM-based sequence alignment, the designed core achieved speed-up of 103x and 8.3x against the HMMER 2.0 and the latest version of HMMER (version 3.0) respectively. On the other hand, the implementation of the gapped BLAST with the two-hit method in hardware achieved a greater than tenfold speed-up compared to the latest NCBI BLAST software. In terms of comparison against other reported FPGA implementations, the proposed normalized performance indicator was used to evaluate the designed architectures fairly. The results showed that the first architecture achieved more than 50 percent improvement, while acceleration of the profile HMM sequence alignment in hardware gained a normalized speed-up of 1.34. In the case of the gapped BLAST with the two-hit method, the designed core achieved 11x speed-up after taking out advantages of the Virtex-5 FPGA. In addition, further analysis was conducted in terms of cost and power performances; it was noted that, the core achieved 0.46 MCUPS per dollar spent and 958.1 MCUPS per watt. This shows that FPGAs can be an attractive platform for high performance computation with advantages of smaller area footprint as well as represent economic ‘green’ solution compared to the other acceleration platforms. Higher throughput can be achieved by redeploying the cores on newer, bigger and faster FPGAs with minimal design effort

    Accelerated Profile HMM Searches

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    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

    ApHMM: Accelerating Profile Hidden Markov Models for Fast and Energy-Efficient Genome Analysis

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    Profile hidden Markov models (pHMMs) are widely employed in various bioinformatics applications to identify similarities between biological sequences, such as DNA or protein sequences. In pHMMs, sequences are represented as graph structures. These probabilities are subsequently used to compute the similarity score between a sequence and a pHMM graph. The Baum-Welch algorithm, a prevalent and highly accurate method, utilizes these probabilities to optimize and compute similarity scores. However, the Baum-Welch algorithm is computationally intensive, and existing solutions offer either software-only or hardware-only approaches with fixed pHMM designs. We identify an urgent need for a flexible, high-performance, and energy-efficient HW/SW co-design to address the major inefficiencies in the Baum-Welch algorithm for pHMMs. We introduce ApHMM, the first flexible acceleration framework designed to significantly reduce both computational and energy overheads associated with the Baum-Welch algorithm for pHMMs. ApHMM tackles the major inefficiencies in the Baum-Welch algorithm by 1) designing flexible hardware to accommodate various pHMM designs, 2) exploiting predictable data dependency patterns through on-chip memory with memoization techniques, 3) rapidly filtering out negligible computations using a hardware-based filter, and 4) minimizing redundant computations. ApHMM achieves substantial speedups of 15.55x - 260.03x, 1.83x - 5.34x, and 27.97x when compared to CPU, GPU, and FPGA implementations of the Baum-Welch algorithm, respectively. ApHMM outperforms state-of-the-art CPU implementations in three key bioinformatics applications: 1) error correction, 2) protein family search, and 3) multiple sequence alignment, by 1.29x - 59.94x, 1.03x - 1.75x, and 1.03x - 1.95x, respectively, while improving their energy efficiency by 64.24x - 115.46x, 1.75x, 1.96x.Comment: Accepted to ACM TAC

    Modern Computational Techniques for the HMMER Sequence Analysis

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    Accelerating HMMER on FPGA using Parallel Prefixes and Reductions

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    HMMER is a widely used tool in bioinformatics, based on Profile Hidden Markov Models. The computation kernels of HMMER i.e. MSV and P7Viterbi are very compute intensive and data dependencies restrict to sequential execution. In this paper, we propose an original parallelization scheme for HMMER by rewriting their mathematical formulation, to expose the hidden potential parallelization opportunities. Our parallelization scheme targets FPGA technology, and our architecture can achieve 10 times speedup compared with that of latest HMMER3 SSE version, while not compromising on sensitivity of original algorithm.HMMER est un outil basĂ© sur la notion profils Ă  base modĂšles de Markov cachĂ©s, qui est trĂšs largement utilisĂ© en bio-informatique. Les parties critiques de l'algorithme (fonctions MSV et P7Viterbi) utilisĂ©es dans HMMER sont trĂšs consommatrices en temps de calcul et rĂ©putĂ©es trĂšs difficiles Ă  parallĂ©liser. Dans cet article, nous proposons un schĂ©ma de parallĂ©lisation original pour HMMER, basĂ© sur une reformulation mathĂ©matique de l'algorithme qui permet de dĂ©couvrir de nouvelles possibilitĂ©s de parallĂ©lisation bien adaptĂ©es Ă  des implantations matĂ©rielles dĂ©diĂ©es. Nous avons implantĂ© cette approche sur un accĂ©lĂ©rateur FPGA et avons mesurĂ© des gains en performance supĂ©rieurs Ă  10 par rapport Ă  l'implĂ©mentation logicielle de HMMER3, laquelle exploite pourtant dĂ©jĂ  de maniĂšre extrĂȘmement efficace les extensions SIMD des processeurs x8

    Parallelization of dynamic programming recurrences in computational biology

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    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
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