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

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

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

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

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

Particle MCMC algorithms and architectures for accelerating inference in state-space models.

Particle Markov Chain Monte Carlo (pMCMC) is a stochastic algorithm designed to generate samples from a probability distribution, when the density of the distribution does not admit a closed form expression. pMCMC is most commonly used to sample from the Bayesian posterior distribution in State-Space Models (SSMs), a class of probabilistic models used in numerous scientific applications. Nevertheless, this task is prohibitive when dealing with complex SSMs with massive data, due to the high computational cost of pMCMC and its poor performance when the posterior exhibits multi-modality. This paper aims to address both issues by: 1) Proposing a novel pMCMC algorithm (denoted ppMCMC), which uses multiple Markov chains (instead of the one used by pMCMC) to improve sampling efficiency for multi-modal posteriors, 2) Introducing custom, parallel hardware architectures, which are tailored for pMCMC and ppMCMC. The architectures are implemented on Field Programmable Gate Arrays (FPGAs), a type of hardware accelerator with massive parallelization capabilities. The new algorithm and the two FPGA architectures are evaluated using a large-scale case study from genetics. Results indicate that ppMCMC achieves 1.96x higher sampling efficiency than pMCMC when using sequential CPU implementations. The FPGA architecture of pMCMC is 12.1x and 10.1x faster than state-of-the-art, parallel CPU and GPU implementations of pMCMC and up to 53x more energy efficient; the FPGA architecture of ppMCMC increases these speedups to 34.9x and 41.8x respectively and is 173x more power efficient, bringing previously intractable SSM-based data analyses within reach.The authors would like to thank the Wellcome Trust (Grant reference 097816/Z/11/A) and the EPSRC (Grant reference EP/I012036/1) for the financial support given to this research project

FPGAs in Bioinformatics: Implementation and Evaluation of Common Bioinformatics Algorithms in Reconfigurable Logic

Life. Much effort is taken to grant humanity a little insight in this fascinating and complex but fundamental topic. In order to understand the relations and to derive consequences humans have begun to sequence their genomes, i.e. to determine their DNA sequences to infer information, e.g. related to genetic diseases. The process of DNA sequencing as well as subsequent analysis presents a computational challenge for recent computing systems due to the large amounts of data alone. Runtimes of more than one day for analysis of simple datasets are common, even if the process is already run on a CPU cluster. This thesis shows how this general problem in the area of bioinformatics can be tackled with reconfigurable hardware, especially FPGAs. Three compute intensive problems are highlighted: sequence alignment, SNP interaction analysis and genotype imputation. In the area of sequence alignment the software BLASTp for protein database searches is exemplarily presented, implemented and evaluated.SNP interaction analysis is presented with three applications performing an exhaustive search for interactions including the corresponding statistical tests: BOOST, iLOCi and the mutual information measurement. All applications are implemented in FPGA-hardware and evaluated, resulting in an impressive speedup of more than in three orders of magnitude when compared to standard computers. The last topic of genotype imputation presents a two-step process composed of the phasing step and the actual imputation step. The focus lies on the phasing step which is targeted by the SHAPEIT2 application. SHAPEIT2 is discussed with its underlying mathematical methods in detail, and finally implemented and evaluated. A remarkable speedup of 46 is reached here as well