A Framework for the Design and Analysis of High-Performance Applications on FPGAs using Partial Reconfiguration

The field-programmable gate array (FPGA) is a dynamically reconfigurable digital logic chip used to implement custom hardware. The large densities of modern FPGAs and the capability of the on-thely reconfiguration has made the FPGA a viable alternative to fixed logic hardware chips such as the ASIC. In high-performance computing, FPGAs are used as co-processors to speed up computationally intensive processes or as autonomous systems that realize a complete hardware application. However, due to the limited capacity of FPGA logic resources, denser FPGAs must be purchased if more logic resources are required to realize all the functions of a complex application. Alternatively, partial reconfiguration (PR) can be used to swap, on demand, idle components of the application with active components. This research uses PR to swap components to improve the performance of the application given the limited logic resources available with smaller but economical FPGAs. The swap is called ”resource sharing PR”. In a pipelined design of multiple hardware modules (pipeline stages), resource sharing PR is a technique that uses PR to improve the performance of pipeline bottlenecks. This is done by reconfiguring other pipeline stages, typically those that are idle waiting for data from a bottleneck, into an additional parallel bottleneck module. The target pipeline of this research is a two-stage “slow-toast” pipeline where the flow of data traversing the pipeline transitions from a relatively slow, bottleneck stage to a fast stage. A two stage pipeline that combines FPGA-based hardware implementations of well-known Bioinformatics search algorithms, the X! Tandem algorithm and the Smith-Waterman algorithm, is implemented for this research; the implemented pipeline demonstrates that characteristics of these algorithm. The experimental results show that, in a database of unknown peptide spectra, when matching spectra with 388 peaks or greater, performing resource sharing PR to instantiate a parallel X! Tandem module is worth the cost for PR. In addition, from timings gathered during experiments, a general formula was derived for determining the value of performing PR upon a fast module

Efficient search and comparison algorithms for 3D protein binding site retrieval and structure alignment from large-scale databases

Finding similar 3D structures is crucial for discovering potential structural, evolutionary, and functional relationships among proteins. As the number of known protein structures has dramatically increased, traditional methods can no longer provide the life science community with the adequate informatics capability needed to conduct large-scale and complex analyses. A suite of high-throughput and accurate protein structure search and comparison methods is essential. To meet the needs of the community, we develop several bioinformatics methods for protein binding site comparison and global structure alignment. First, we developed an efficient protein binding site search that is based on extracting geometric features both locally and globally. The main idea of this work was to capture spatial relationships among landmarks of binding site surfaces and bfuild a vocabulary of visual words to represent the characteristics of the surfaces. A vector model was then used to speed up the search of similar surfaces that share similar visual words with the query interface. Second, we developed an approach for accurate protein binding site comparison. Our algorithm provides an accurate binding site alignment by applying a two-level heuristic process which progressively refines alignment results from coarse surface point level to accurate residue atom level. This setting allowed us to explore different combinations of pairs of corresponding residues, thus improving the alignment quality of the binding site surfaces. Finally, we introduced a parallel algorithm for global protein structure alignment. Specifically, to speed up the time-consuming structure alignment process of protein 3D structures, we designed a parallel protein structure alignment framework to exploit the parallelism of Graphics Processing Units (GPUs). As a general-purpose GPU platform, the framework is capable of parallelizing traditional structure alignment algorithms. Our findings can be applied in various research areas, such as prediction of protein inte

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

Tighter Connections Between Formula-SAT and Shaving Logs

A noticeable fraction of Algorithms papers in the last few decades improve the running time of well-known algorithms for fundamental problems by logarithmic factors. For example, the $O(n^2)$ dynamic programming solution to the Longest Common Subsequence problem (LCS) was improved to $O(n^2/\log^2 n)$ in several ways and using a variety of ingenious tricks. This line of research, also known as "the art of shaving log factors", lacks a tool for proving negative results. Specifically, how can we show that it is unlikely that LCS can be solved in time $O(n^2/\log^3 n)$? Perhaps the only approach for such results was suggested in a recent paper of Abboud, Hansen, Vassilevska W. and Williams (STOC'16). The authors blame the hardness of shaving logs on the hardness of solving satisfiability on Boolean formulas (Formula-SAT) faster than exhaustive search. They show that an $O(n^2/\log^{1000} n)$ algorithm for LCS would imply a major advance in circuit lower bounds. Whether this approach can lead to tighter barriers was unclear. In this paper, we push this approach to its limit and, in particular, prove that a well-known barrier from complexity theory stands in the way for shaving five additional log factors for fundamental combinatorial problems. For LCS, regular expression pattern matching, as well as the Fr\'echet distance problem from Computational Geometry, we show that an $O(n^2/\log^{7+\varepsilon} n)$ runtime would imply new Formula-SAT algorithms. Our main result is a reduction from SAT on formulas of size $s$ over $n$ variables to LCS on sequences of length $N=2^{n/2} \cdot s^{1+o(1)}$. Our reduction is essentially as efficient as possible, and it greatly improves the previously known reduction for LCS with $N=2^{n/2} \cdot s^c$, for some $c \geq 100$

DynaProg for Scala

Dynamic programming is an algorithmic technique to solve problems that follow the Bellman’s principle: optimal solutions depends on optimal sub-problem solutions. The core idea behind dynamic programming is to memoize intermediate results into matrices to avoid multiple computations. Solving a dynamic programming problem consists of two phases: filling one or more matrices with intermediate solutions for sub-problems and recomposing how the final result was constructed (backtracking). In textbooks, problems are usually described in terms of recurrence relations between matrices elements. Expressing dynamic programming problems in terms of recursive formulae involving matrix indices might be difficult, if often error prone, and the notation does not capture the essence of the underlying problem (for example aligning two sequences). Moreover, writing correct and efficient parallel implementation requires different competencies and often a significant amount of time. In this project, we present DynaProg, a language embedded in Scala (DSL) to address dynamic programming problems on heterogeneous platforms. DynaProg allows the programmer to write concise programs based on ADP [1], using a pair of parsing grammar and algebra; these program can then be executed either on CPU or on GPU. We evaluate the performance of our implementation against existing work and our own hand-optimized baseline implementations for both the CPU and GPU versions. Experimental results show that plain Scala has a large overhead and is recommended to be used with small sequences (≤1024) whereas the generated GPU version is comparable with existing implementations: matrix chain multiplication has the same performance as our hand-optimized version (142% of the execution time of [2]) for a sequence of 4096 matrices, Smith-Waterman is twice slower than [3] on a pair of sequences of 6144 elements, and RNA folding is on par with [4] (95% running time) for sequences of 4096 elements. [1] Robert Giegerich and Carsten Meyer. Algebraic Dynamic Programming. [2] Chao-Chin Wu, Jenn-Yang Ke, Heshan Lin and Wu Chun Feng. Optimizing dynamic programming on graphics processing units via adaptive thread-level parallelism. [3] Edans Flavius de O. Sandes, Alba Cristina M. A. de Melo. Smith-Waterman alignment of huge sequences with GPU in linear space. [4] Guillaume Rizk and Dominique Lavenier. GPU accelerated RNA folding algorithm

Inference of Many-Taxon Phylogenies

Phylogenetic trees are tree topologies that represent the evolutionary history of a set of organisms. In this thesis, we address computational challenges related to the analysis of large-scale datasets with Maximum Likelihood based phylogenetic inference. We have approached this using different strategies: reduction of memory requirements, reduction of running time, and reduction of man-hours

FPGAs in der Bioinformatik: Implementierung und Evaluierung bekannter bioinformatischer Algorithmen in rekonfigurierbarer Logik

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.Das Leben. Sehr viel Aufwand wird getrieben um der Menschheit einen Einblick in dieses faszinierende und komplexe, aber fundamentale Thema zu erlauben. Um Zusammenhänge zu verstehen und Folgen ableiten zu können hat der Mensch begonnen sein Genom zu sequenzieren, d.h. seine DNA zu bestimmen um daraus Informationen, z.B. in Bezug auf Erbkrankheiten folgern zu können. Der Prozess der DNA-Sequenzierung sowie die darauffolgenden Analysen sind schon allein wegen der riesigen Datenmengen eine Herausforderung für aktuelle Rechensysteme. Laufzeiten von über einen Tag für die Analyse einfacher Datensätze sind üblich, selbst wenn der Prozess bereits auf einem Computercluster ausgeführt wird. Diese Arbeit zeigt, wie dieses gängige Problem im Bereich der Bioinformatik mit rekonfigurierbarer Hardware, speziell FPGAs, angegangen werden kann. Es werden drei rechenintensive Themengebiete hervorgehoben: Sequenzalignment, SNP-Interaktionsanalyse und Genotyp-Imputation. Beispielhaft wird im Bereich des Sequenzalignments die Software BLASTp für die Suche in Proteinsequenzdatenbanken vorgestellt, implementiert und evaluiert. Die SNP-Interaktionsanalyse wird mit drei Verfahren zur vollständigen Suche von Interaktionen inklusive des dazugehörigen statistischen Tests vorgestellt: BOOST, iLOCi und die Messung der Transinformation. Alle Verfahren werden auf FPGA-Hardware implementiert und evaluiert, mit einer bestechenden Beschleunigung im dreistelligen Bereich gegenüber Standard-Rechnern. Das letzte Gebiet der Genotyp-Imputierung ist ein zweiteiliges Verfahren bestehend aus dem Phasing und der eigentlichen Imputation. Der Schwerpunkt liegt im Phasing-Schritt, der mit dem SHAPEIT2-Tool adressiert wird. SHAPEIT2 wird ausführlich mit den zugrunde liegenden mathematischen Methoden diskutiert, und schließlich implementiert und evaluiert. Auch hier wird ein beachtlicher Speedup von 46 erreicht

Phylogeny-Aware Placement and Alignment Methods for Short Reads

In recent years bioinformatics has entered a new phase: New sequencing methods, generally referred to as Next Generation Sequencing (NGS) have become widely available. This thesis introduces algorithms for phylogeny aware analysis of short sequence reads, as generated by NGS methods in the context of metagenomic studies. A considerable part of this work focuses on the technical (w.r.t. performance) challenges of these new algorithms, which have been developed specifically to exploit parallelism