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

Hardware implementation of non-bonded forces in molecular dynamics simulations

Molecular Dynamics is a computational method based on classical mechanics to describe the behavior of a molecular system. This method is used in biomolecular simulations, which are intended to contribute to the study and advance of nanotechnology, medicine, chemistry and biology. Software implementations of Molecular Dynamics simulations can spend most of time computing the non-bonded interactions. This work presents the design and implementation of an FPGA-based coprocessor that accelerates MD simulations by computing in parallel the non-bonded interactions, specifically, the van der Waals and the electrostatic interactions. These interactions are modeled as the Lennard-Jones 6-12 potential and the direct-space Ewald summation, respectively. In addition, this work introduces a novel variable transformation of the potential energy functions, and a novel interpolation method with pseudo-floating-point representation to compute the short-range forces. Also, it uses a combination of fixed-point and floating-point arithmetic to obtain the best of both representations. The FPGA coprocessor is a memory-mapped system connected to a host by PCI Express, and is provided with interruption capabilities to improve parallelization. Its main block is based on a single functional pipeline, and is connected via Avalon Bus to other peripherals such as the PCIe Hard-IP and the SG-DMA. It is implemented on an Altera¿s EP2AGX125EF35C4 device, can process 16k particles, and is configured to store up to 16 different types of particles. Simulations in a custom C-application for MD that only computes non-bonded forces become up to 12.5x faster using the FPGA coprocessor when considering 12500 atoms.PregradoINGENIERO(A) EN ELECTRÓNIC

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

ATOMISTIC SIMULATIONS OF INTRINSICALLY DISORDERED PROTEIN FOLDING AND DYNAMICS

Intrinsically disordered proteins (IDPs) are crucial in biology and human diseases, necessitating a comprehensive understanding of their structure, dynamics, and interactions. Atomistic simulations have emerged as a key tool for unraveling the molecular intricacies and establishing mechanistic insights into how these proteins facilitate diverse biological functions. However, achieving accurate simulations requires both an appropriate protein force field capable of describing the energy landscape of functionally relevant IDP conformations and sufficient conformational sampling to capture the free energy landscape of IDP dynamics. These factors are fundamental in comprehending potential IDP structures, dynamics, and interactions. I first conducted explicit solvent simulations to assess the performance of two state-of-the-art protein force fields, namely CHARMM36m and a99SB-disp, in capturing the stability of small protein-protein interactions. To evaluate their accuracy, I selected a set of 46 amino acid backbone and side chain pairs with representative configurations and computed the free energy profiles of their interactions. The results demonstrated that CHARMM36m consistently predicted stronger protein-protein interactions compared to a99SB-disp. Notably, the most significant overestimation in CHARMM36m occurred in charged pairs involving Arg and Glu side chains, with an overestimation of up to 2.9 kcal/mol. Through free energy decomposition analysis, I determined that these overestimations were primarily driven by protein-water electrostatic interactions rather than van der Waals (vdW) interactions. Consequently, these findings suggest that careful rebalancing of electrostatic interactions should be considered in the further optimization of protein force fields. In order to enhance the conformational sampling of IDPs, I developed an integrated approach that combines an improved implicit solvent model called Generalized Born with molecular volume and solvent accessible surface area (GBMV2/SA) with a multiscale enhanced sampling (MSES) technique. To make this approach more efficient, I implemented it as a standalone OpenMM plugin on Graphics Processing Units (GPUs). The results demonstrated that the GPU-GBMV2/SA model achieved numerical equivalence to the original CPU-GBMV2/SA models, while providing a remarkable ~60x speedup on a single NVIDIA TITAN X (Pascal) graphics card for molecular dynamic simulations of both folded and unstructured proteins. This significant acceleration greatly facilitated the application of the approach in biomolecular simulations. In addition, I conducted an evaluation of the reliability of GBMV2/SA models in simulating both folded and unfolded proteins. The results revealed that the GBMV2/SA model accurately describes small proteins, but its applicability is limited when it comes to larger proteins such as KID and p53-TAD proteins. This limitation can be attributed to the absence of long-range solute-solvent dispersion interactions in the model. To address this issue, I introduced a comprehensive treatment of nonpolar solvation free energy called GBMV2/NP model. Unfortunately, the GBMV2/NP model exhibited a destabilizing effect on well-folded proteins, particularly larger ones, due to an inaccurate representation of the repulsive solvent accessible surface area (SASA) model caused by the utilization of unphysical van der Waals volume. This observation highlights the need for further improvements in accurately describing the nonpolar term in the model

Software for Exascale Computing - SPPEXA 2016-2019

This open access book summarizes the research done and results obtained in the second funding phase of the Priority Program 1648 "Software for Exascale Computing" (SPPEXA) of the German Research Foundation (DFG) presented at the SPPEXA Symposium in Dresden during October 21-23, 2019. In that respect, it both represents a continuation of Vol. 113 in Springer’s series Lecture Notes in Computational Science and Engineering, the corresponding report of SPPEXA’s first funding phase, and provides an overview of SPPEXA’s contributions towards exascale computing in today's sumpercomputer technology. The individual chapters address one or more of the research directions (1) computational algorithms, (2) system software, (3) application software, (4) data management and exploration, (5) programming, and (6) software tools. The book has an interdisciplinary appeal: scholars from computational sub-fields in computer science, mathematics, physics, or engineering will find it of particular interest

A Hybrid-parallel Architecture for Applications in Bioinformatics

Since the advent of Next Generation Sequencing (NGS) technology, the amount of data from whole genome sequencing has been rising fast. In turn, the availability of these resources led to the tapping of whole new research fields in molecular and cellular biology, producing even more data. On the other hand, the available computational power is only increasing linearly. In recent years though, special-purpose high-performance devices started to become prevalent in today’s scientific data centers, namely graphics processing units (GPUs) and, to a lesser extent, field-programmable gate arrays (FPGAs). Driven by the need for performance, developers started porting regular applications to GPU frameworks and FPGA configurations to exploit the special operations only these devices may perform in a timely manner. However, applications using both accelerator technologies are still rare. Major challenges in joint GPU/FPGA application development include the required deep knowledge of associated programming paradigms and the efficient communication both types of devices. In this work, two algorithms from bioinformatics are implemented on a custom hybrid-parallel hardware architecture and a highly concurrent software platform. It is shown that such a solution is not only possible to develop but also its ability to outperform implementations on similar- sized GPU or FPGA clusters in terms of both performance and energy consumption. Both algorithms analyze case/control data from genome- wide association studies to find interactions between two or three genes with different methods. Especially in the latter case, the newly available calculation power and method enables analyses of large data sets for the first time without occupying whole data centers for weeks. The success of the hybrid-parallel architecture proposal led to the development of a high- end array of FPGA/GPU accelerator pairs to provide even better runtimes and more possibilities

Finding, Measuring, and Reducing Inefficiencies in Contemporary Computer Systems

Computer systems have become increasingly diverse and specialized in recent years. This complexity supports a wide range of new computing uses and users, but is not without cost: it has become difficult to maintain the efficiency of contemporary general purpose computing systems. Computing inefficiencies, which include nonoptimal runtimes, excessive energy use, and limits to scalability, are a serious problem that can result in an inability to apply computing to solve the world's most important problems. Beyond the complexity and vast diversity of modern computing platforms and applications, a number of factors make improving general purpose efficiency challenging, including the requirement that multiple levels of the computer system stack be examined, that legacy hardware devices and software may stand in the way of achieving efficiency, and the need to balance efficiency with reusability, programmability, security, and other goals. This dissertation presents five case studies, each demonstrating different ways in which the measurement of emerging systems can provide actionable advice to help keep general purpose computing efficient. The first of the five case studies is Parallel Block Vectors, a new profiling method for understanding parallel programs with a fine-grained, code-centric perspective aids in both future hardware design and in optimizing software to map better to existing hardware. Second is a project that defines a new way of measuring application interference on a datacenter's worth of chip-multiprocessors, leading to improved scheduling where applications can more effectively utilize available hardware resources. Next is a project that uses the GT-Pin tool to define a method for accelerating the simulation of GPGPUs, ultimately allowing for the development of future hardware with fewer inefficiencies. The fourth project is an experimental energy survey that compares and combines the latest energy efficiency solutions at different levels of the stack to properly evaluate the state of the art and to find paths forward for future energy efficiency research. The final project presented is NRG-Loops, a language extension that allows programs to measure and intelligently adapt their own power and energy use