Computing Platforms for Big Biological Data Analytics: Perspectives and Challenges.

The last decade has witnessed an explosion in the amount of available biological sequence data, due to the rapid progress of high-throughput sequencing projects. However, the biological data amount is becoming so great that traditional data analysis platforms and methods can no longer meet the need to rapidly perform data analysis tasks in life sciences. As a result, both biologists and computer scientists are facing the challenge of gaining a profound insight into the deepest biological functions from big biological data. This in turn requires massive computational resources. Therefore, high performance computing (HPC) platforms are highly needed as well as efficient and scalable algorithms that can take advantage of these platforms. In this paper, we survey the state-of-the-art HPC platforms for big biological data analytics. We first list the characteristics of big biological data and popular computing platforms. Then we provide a taxonomy of different biological data analysis applications and a survey of the way they have been mapped onto various computing platforms. After that, we present a case study to compare the efficiency of different computing platforms for handling the classical biological sequence alignment problem. At last we discuss the open issues in big biological data analytics

FPGA acceleration of sequence analysis tools in bioinformatics

Thesis (Ph.D.)--Boston UniversityWith advances in biotechnology and computing power, biological data are being produced at an exceptional rate. The purpose of this study is to analyze the application of FPGAs to accelerate high impact production biosequence analysis tools. Compared with other alternatives, FPGAs offer huge compute power, lower power consumption, and reasonable flexibility. BLAST has become the de facto standard in bioinformatic approximate string matching and so its acceleration is of fundamental importance. It is a complex highly-optimized system, consisting of tens of thousands of lines of code and a large number of heuristics. Our idea is to emulate the main phases of its algorithm on FPGA. Utilizing our FPGA engine, we quickly reduce the size of the database to a small fraction, and then use the original code to process the query. Using a standard FPGA-based system, we achieved 12x speedup over a highly optimized multithread reference code. Multiple Sequence Alignment (MSA)--the extension of pairwise Sequence Alignment to multiple Sequences--is critical to solve many biological problems. Previous attempts to accelerate Clustal-W, the most commonly used MSA code, have directly mapped a portion of the code to the FPGA. We use a new approach: we apply prefiltering of the kind commonly used in BLAST to perform the initial all-pairs alignments. This results in a speedup of from 8Ox to 190x over the CPU code (8 cores). The quality is comparable to the original according to a commonly used benchmark suite evaluated with respect to multiple distance metrics. The challenge in FPGA-based acceleration is finding a suitable application mapping. Unfortunately many software heuristics do not fall into this category and so other methods must be applied. One is restructuring: an entirely new algorithm is applied. Another is to analyze application utilization and develop accuracy/performance tradeoffs. Using our prefiltering approach and novel FPGA programming models we have achieved significant speedup over reference programs. We have applied approximation, seeding, and filtering to this end. The bulk of this study is to introduce the pros and cons of these acceleration models for biosequence analysis tools

ROACH accelerated BLAST

Includes abstract.Includes bibliographical references (p. 115-118).Reconfigurable computing, in recent years, has been taking great strides in becoming part of mainstream computing largely due to the rapid growth in the size of FPGAs and their ability to adapt to certain complex applications efficiently. This dissertation investigates the reuse of application specific hardware developed for radio astronomy in accelerating a popular bioinformatics algorithm

Mapping applications onto FPGA-centric clusters

High Performance Computing (HPC) is becoming increasingly important throughout science and engineering as ever more complex problems must be solved through computational simulations. In these large computational applications, the latency of communication between processing nodes is often the key factor that limits performance. An emerging alternative computer architecture that addresses the latency problem is the FPGA-centric cluster (FCC); in these systems, the devices (FPGAs) are directly interconnected and thus many layers of hardware and software are avoided. The result can be scalability not currently achievable with other technologies. In FCCs, FPGAs serve multiple functions: accelerator, network interface card (NIC), and router. Moreover, because FPGAs are configurable, there is substantial opportunity to tailor the router hardware to the application; previous work has demonstrated that such application-aware configuration can effect a substantial improvement in hardware efficiency. One constraint of FCCs is that it is convenient for their interconnect to be static, direct, and have a two or three dimensional mesh topology. Thus, applications that are naturally of a different dimensionality (have a different logical topology) from that of the FCC must be remapped to obtain optimal performance. In this thesis we study various aspects of the mapping problem for FCCs. There are two major research thrusts. The first is finding the optimal mapping of logical to physical topology. This problem has received substantial attention by both the theory community, where topology mapping is referred to as graph embedding, and by the High Performance Computing (HPC) community, where it is a question of process placement. We explore the implications of the different mapping strategies on communication behavior in FCCs, especially on resulting load imbalance. The second major research thrust is built around the hypothesis that applications that need to be remapped (due to differing logical and physical topologies) will have different optimal router configurations from those applications that do not. For example, due to remapping, some virtual or physical communication links may have little occupancy; therefore fewer resources should be allocated to them. Critical here is the creation of a new set of parameterized hardware features that can be configured to best handle load imbalances caused by remapping. These two thrusts form a codesign loop: certain mapping algorithms may be differentially optimal due to application-aware router reconfiguration that accounts for this mapping. This thesis has four parts. The first part introduces the background and previous work related to communication in general and, in particular, how it is implemented in FCCs. We build on previous work on application-aware router configuration. The second part introduces topology mapping mechanisms including those derived from graph embeddings and a greedy algorithm commonly used in HPC. In the third part, topology mappings are evaluated for performance and imbalance; we note that different mapping strategies lead to different imbalances both in the overall network and in each node. The final part introduces reconfigure router design that allocates resources based on different imbalance situations caused by different mapping behaviors

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

Bioinformatics

This book is divided into different research areas relevant in Bioinformatics such as biological networks, next generation sequencing, high performance computing, molecular modeling, structural bioinformatics, molecular modeling and intelligent data analysis. Each book section introduces the basic concepts and then explains its application to problems of great relevance, so both novice and expert readers can benefit from the information and research works presented here

FPGA acceleration of DNA sequence alignment: design analysis and optimization

Existing FPGA accelerators for short read mapping often fail to utilize the complete biological information in sequencing data for simple hardware design, leading to missed or incorrect alignment. In this work, we propose a runtime reconfigurable alignment pipeline that considers all information in sequencing data for the biologically accurate acceleration of short read mapping. We focus our efforts on accelerating two string matching techniques: FM-index and the Smith-Waterman algorithm with the affine-gap model which are commonly used in short read mapping. We further optimize the FPGA hardware using a design analyzer and merger to improve alignment performance. The contributions of this work are as follows. 1. We accelerate the exact-match and mismatch alignment by leveraging the FM-index technique. We optimize memory access by compressing the data structure and interleaving the access with multiple short reads. The FM-index hardware also considers complete information in the read data to maximize accuracy. 2. We propose a seed-and-extend model to accelerate alignment with indels. The FM-index hardware is extended to support the seeding stage while a Smith-Waterman implementation with the affine-gap model is developed on FPGA for the extension stage. This model can improve the efficiency of indel alignment with comparable accuracy versus state-of-the-art software. 3. We present an approach for merging multiple FPGA designs into a single hardware design, so that multiple place-and-route tasks can be replaced by a single task to speed up functional evaluation of designs. We first experiment with this approach to demonstrate its feasibility for different designs. Then we apply this approach to optimize one of the proposed FPGA aligners for better alignment performance.Open Acces

IMPROVING BWA-MEM WITH GPU PARALLEL COMPUTING

Due to the many advances made in designing algorithms, especially the ones used in bioinformatics, it is becoming harder and harder to improve their efficiencies. Therefore, hardware acceleration using General-Purpose computing on Graphics Processing Unit has become a popular choice. BWA-MEM is an important part of the BWA software package for sequence mapping. Because of its high speed and accuracy, we choose to parallelize the popular short DNA sequence mapper. BWA has been a prevalent single node tool in genome alignment, and it has been widely studied for acceleration for a long time since the first version of the BWA package came out. This thesis presents the Big Data GPGPU distributed BWA-MEM, a tool that combines GPGPU acceleration and distributed computing. The four hardware parallelization techniques used are CPU multi-threading, GPU paralleled, CPU distributed, and GPU distributed. The GPGPU distributed software typically outperforms other parallelization versions. The alignment is performed on a distributed network, and each node in the network executes a separate GPGPU paralleled version of the software. We parallelize the chain2aln function in three levels. In Level 1, the function ksw\_extend2, an algorithm based on Smith-Waterman, is parallelized to handle extension on one side of the seed. In Level 2, the function chain2aln is parallelized to handle chain extension, where all seeds within the same chain are extended. In Level 3, part of the function mem\_align1\_core is parallelized for extending multiple chains. Due to the program's complexity, the parallelization work was limited at the GPU version of ksw\_extend2 parallelization Level 3. However, we have successfully combined Spark with BWA-MEM and ksw\_extend2 at parallelization Level 1, which has shown that the proposed framework is possible. The paralleled Level 3 GPU version of ksw\_extend2 demonstrated noticeable speed improvement with the test data set