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

Hardware acceleration of the pair HMM algorithm for DNA variant calling

With the advent of several accurate and sophisticated statistical algorithms and pipelines for DNA sequence analysis, it is becoming increasingly possible to translate raw sequencing data into biologically meaningful information for further clinical analysis and processing. However, given the large volume of the data involved, even modestly complex algorithms would require a prohibitively long time to complete. Hence it is urgent to explore non-conventional implementation platforms to accelerate genomics research. In this thesis, we present a Field-Programmable Gate Array (FPGA) accelerated implementation of the Pair Hidden Markov Model (Pair HMM) forward algorithm, the performance bottleneck in the HaplotypeCaller, a critical function in the popular Genome Analysis Toolkit (GATK) variant calling tool. We introduce the PE ring structure which, thanks to the fine-grained parallelism allowed by the FPGA, can be built into various configurations striking a trade-off between Instruction-Level Parallelism (ILP) and data parallelism. We investigate the resource utilization and performance of different configurations. Our solution can achieve a speed-up of up to 487x compared to the C++ baseline implementation on CPU and 1.56x compared to the previous best hardware implementation

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 ‘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

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

Exploration of GPU acceleration for pair-HMM algorithm and its application in the DNA alignment problem

The hidden Markov model, known as HMM, is an important type of statistical model with extensive application in estimating hidden parameters and decoding observed Markov chains. On top of the HMM, the Pair-HMM Algorithm with Halotype-Caller is developed as a popular solution for the DNA alignment problem. For two aligned sequences of DNA observations, one named as reference, and the other one named as read, there are only three possible hidden states, i.e. match (A , A), insertion (- , A), and deletion (A , -). However, what we could observe by DNA sequencing in real-life is the summation of the possibilities for match, insertion, and deletion as macrostates. In order to determine the alignment with maximum probability, we need to score each possible pairwise alignment and which leads to a computationally intensive problem that usually contributes to the most latency in a variant calling with the GATK HaplotypeCaller. In the CPU implementation of a proper Pair-HMM forward algorithm, there are 7 multiply-accumulate operations for each ( i , j ) location on the read-reference matrix. Moreover, since transitions and emission matrices are fixed throughout a single alignment process, a CUDA implementation with single-precision floating-point is proposed to accelerate the Pair-HMM forward algorithm. CUDA implementation with minibatch and states-parallelization, along with the use of float32, gives us an around 22.6x speedup compared to the CPU implementation. While it comes with a price, using single-precision instead of double-precision floating-point introduces a more serious under flow problem at the beginning of the alignment scoring process. A normalization technique is used to help fix this problem.Ope

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

Hardware acceleration of the trace transform for vision applications

Computer Vision is a rapidly developing field in which machines process visual data to extract meaningful information. Digitised images in their pixels and bits serve no purpose of their own. It is only by interpreting the data, and extracting higher level information that a scene can be understood. The algorithms that enable this process are often complex, and data-intensive, limiting the processing rate when implemented in software. Hardware-accelerated implementations provide a significant performance boost that can enable real- time processing. The Trace Transform is a newly proposed algorithm that has been proven effective in image categorisation and recognition tasks. It is flexibly defined allowing the mathematical details to be tailored to the target application. However, it is highly computationally intensive, which limits its applications. Modern heterogeneous FPGAs provide an ideal platform for accelerating the Trace transform for real-time performance, while also allowing an element of flexibility, which highly suits the generality of the Trace transform. This thesis details the implementation of an extensible Trace transform architecture for vision applications, before extending this architecture to a full flexible platform suited to the exploration of Trace transform applications. As part of the work presented, a general set of architectures for large-windowed median and weighted median filters are presented as required for a number of Trace transform implementations. Finally an acceleration of Pseudo 2-Dimensional Hidden Markov Model decoding, usable in a person detection system, is presented. Such a system can be used to extract frames of interest from a video sequence, to be subsequently processed by the Trace transform. All these architectures emphasise the need for considered, platform-driven design in achieving maximum performance through hardware acceleration

Doctor of Philosophy

dissertationThe embedded system space is characterized by a rapid evolution in the complexity and functionality of applications. In addition, the short time-to-market nature of the business motivates the use of programmable devices capable of meeting the conflicting constraints of low-energy, high-performance, and short design times. The keys to achieving these conflicting constraints are specialization and maximally extracting available application parallelism. General purpose processors are flexible but are either too power hungry or lack the necessary performance. Application-specific integrated circuits (ASICS) efficiently meet the performance and power needs but are inflexible. Programmable domain-specific architectures (DSAs) are an attractive middle ground, but their design requires significant time, resources, and expertise in a variety of specialties, which range from application algorithms to architecture and ultimately, circuit design. This dissertation presents CoGenE, a design framework that automates the design of energy-performance-optimal DSAs for embedded systems. For a given application domain and a user-chosen initial architectural specification, CoGenE consists of a a Compiler to generate execution binary, a simulator Generator to collect performance/energy statistics, and an Explorer that modifies the current architecture to improve energy-performance-area characteristics. The above process repeats automatically until the user-specified constraints are achieved. This removes or alleviates the time needed to understand the application, manually design the DSA, and generate object code for the DSA. Thus, CoGenE is a new design methodology that represents a significant improvement in performance, energy dissipation, design time, and resources. This dissertation employs the face recognition domain to showcase a flexible architectural design methodology that creates "ASIC-like" DSAs. The DSAs are instruction set architecture (ISA)-independent and achieve good energy-performance characteristics by coscheduling the often conflicting constraints of data access, data movement, and computation through a flexible interconnect. This represents a significant increase in programming complexity and code generation time. To address this problem, the CoGenE compiler employs integer linear programming (ILP)-based 'interconnect-aware' scheduling techniques for automatic code generation. The CoGenE explorer employs an iterative technique to search the complete design space and select a set of energy-performance-optimal candidates. When compared to manual designs, results demonstrate that CoGenE produces superior designs for three application domains: face recognition, speech recognition and wireless telephony. While CoGenE is well suited to applications that exhibit a streaming behavior, multithreaded applications like ray tracing present a different but important challenge. To demonstrate its generality, CoGenE is evaluated in designing a novel multicore N-wide SIMD architecture, known as StreamRay, for the ray tracing domain. CoGenE is used to synthesize the SIMD execution cores, the compiler that generates the application binary, and the interconnection subsystem. Further, separating address and data computations in space reduces data movement and contention for resources, thereby significantly improving performance compared to existing ray tracing approaches