6 research outputs found
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 âmultiple segment Viterbiâ (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 âsparse rescalingâ. 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
High Performance Database Searching with HMMer on FPGAs
Profile Hidden Markov Models (profile HMMs) are used as a popular bioinformatics tool for sensitive database searching, e.g. a set of not annotated protein sequences is compared to a database of profile HMMs to detect functional similarities. HMMer is a commonly used package for profile HMM-based methods. However, searching large databases with HMMer suffers from long runtimes on traditional computer architectures. These runtime requirements are likely to become even more severe due to the rapid growth in size of both sequence and model databases. In this paper, we present a new reconfigurable architecture to accelerate HMMer database searching. It is described how this leads to significant runtime savings on off-the-shelf fieldprogrammable gate arrays (FPGAs). 1
High performance reconfigurable architectures for biological sequence alignment
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 âgreenâ 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