Efficient analysis and storage of large-scale genomic data

The impending advent of population-scaled sequencing cohorts involving tens of millions of individuals with matched phenotypic measurements will produce unprecedented volumes of genetic data. Storing and analysing such gargantuan datasets places computational performance at a pivotal position in medical genomics. In this thesis, I explore the potential for accelerating and parallelizing standard genetics workflows, file formats, and algorithms using both hardware-accelerated vectorization, parallel and distributed algorithms, and heterogeneous computing. First, I describe a novel bit-counting operation termed the positional population-count, which can be used together with succinct representations and standard efficient operations to accelerate many genetic calculations. In order to enable the use of this new operator and the canonical population count on any target machine I developed a unified low-level library using CPU dispatching to select the optimal method contingent on the available instruction set architecture and the given input size at run-time. As a proof-of-principle application, I apply the positional population-count operator to computing quality control-related summary statistics for terabyte-scaled sequencing readsets with >3,800-fold speed improvements. As another application, I describe a framework for efficiently computing the cardinality of set intersection using these operators and applied this framework to efficiently compute genome-wide linkage-disequilibrium in datasets with up to 67 million samples resulting in up to >60-fold improvements in speed for dense genotypic vectors and up to >250,000-fold savings in memory and >100,000-fold improvement in speed for sparse genotypic vectors. I next describe a framework for handling the terabytes of compressed output data and describe graphical routines for visualizing long-range linkage-disequilibrium blocks as seen over many human centromeres. Finally, I describe efficient algorithms for storing and querying very large genetic datasets and specialized algorithms for the genotype component of such datasets with >10,000-fold savings in memory compared to the current interchange format.Wellcome Trus

Evaluation of low-power architectures in a scientific computing environment

HPC (High Performance Computing) represents, together with theory and experiments, the third pillar of science. Through HPC, scientists can simulate phenomena otherwise impossible to study. The need of performing larger and more accurate simulations requires to HPC to improve every day. HPC is constantly looking for new computational platforms that can improve cost and power efficiency. The Mont-Blanc project is a EU funded research project that targets to study new hardware and software solutions that can improve efficiency of HPC systems. The vision of the project is to leverage the fast growing market of mobile devices to develop the next generation supercomputers. In this work we contribute to the objectives of the Mont-Blanc project by evaluating performance of production scientific applications on innovative low power architectures. In order to do so, we describe our experiences porting and evaluating sate of the art scientific applications on the Mont-Blanc prototype, the first HPC system built with commodity low power embedded technology. We then extend our study to compare off-the-shelves ARMv8 platforms. We finally discuss the most impacting issues encountered during the development of the Mont-Blanc prototype system

Efficient Storage of Genomic Sequences in High Performance Computing Systems

ABSTRACT: In this dissertation, we address the challenges of genomic data storage in high performance computing systems. In particular, we focus on developing a referential compression approach for Next Generation Sequence data stored in FASTQ format files. The amount of genomic data available for researchers to process has increased exponentially, bringing enormous challenges for its efficient storage and transmission. General-purpose compressors can only offer limited performance for genomic data, thus the need for specialized compression solutions. Two trends have emerged as alternatives to harness the particular properties of genomic data: non-referential and referential compression. Non-referential compressors offer higher compression rations than general purpose compressors, but still below of what a referential compressor could theoretically achieve. However, the effectiveness of referential compression depends on selecting a good reference and on having enough computing resources available. This thesis presents one of the first referential compressors for FASTQ files. We first present a comprehensive analytical and experimental evaluation of the most relevant tools for genomic raw data compression, which led us to identify the main needs and opportunities in this field. As a consequence, we propose a novel compression workflow that aims at improving the usability of referential compressors. Subsequently, we discuss the implementation and performance evaluation for the core of the proposed workflow: a referential compressor for reads in FASTQ format that combines local read-to-reference alignments with a specialized binary-encoding strategy. The compression algorithm, named UdeACompress, achieved very competitive compression ratios when compared to the best compressors in the current state of the art, while showing reasonable execution times and memory use. In particular, UdeACompress outperformed all competitors when compressing long reads, typical of the newest sequencing technologies. Finally, we study the main aspects of the data-level parallelism in the Intel AVX-512 architecture, in order to develop a parallel version of the UdeACompress algorithms to reduce the runtime. Through the use of SIMD programming, we managed to significantly accelerate the main bottleneck found in UdeACompress, the Suffix Array Construction

An Experimental Evaluation of Machine Learning Training on a Real Processing-in-Memory System

Training machine learning (ML) algorithms is a computationally intensive process, which is frequently memory-bound due to repeatedly accessing large training datasets. As a result, processor-centric systems (e.g., CPU, GPU) suffer from costly data movement between memory units and processing units, which consumes large amounts of energy and execution cycles. Memory-centric computing systems, i.e., with processing-in-memory (PIM) capabilities, can alleviate this data movement bottleneck. Our goal is to understand the potential of modern general-purpose PIM architectures to accelerate ML training. To do so, we (1) implement several representative classic ML algorithms (namely, linear regression, logistic regression, decision tree, K-Means clustering) on a real-world general-purpose PIM architecture, (2) rigorously evaluate and characterize them in terms of accuracy, performance and scaling, and (3) compare to their counterpart implementations on CPU and GPU. Our evaluation on a real memory-centric computing system with more than 2500 PIM cores shows that general-purpose PIM architectures can greatly accelerate memory-bound ML workloads, when the necessary operations and datatypes are natively supported by PIM hardware. For example, our PIM implementation of decision tree is $27\times$ faster than a state-of-the-art CPU version on an 8-core Intel Xeon, and $1.34\times$ faster than a state-of-the-art GPU version on an NVIDIA A100. Our K-Means clustering on PIM is $2.8\times$ and $3.2\times$ than state-of-the-art CPU and GPU versions, respectively. To our knowledge, our work is the first one to evaluate ML training on a real-world PIM architecture. We conclude with key observations, takeaways, and recommendations that can inspire users of ML workloads, programmers of PIM architectures, and hardware designers & architects of future memory-centric computing systems

Hardware-Aware Algorithm Designs for Efficient Parallel and Distributed Processing

The introduction and widespread adoption of the Internet of Things, together with emerging new industrial applications, bring new requirements in data processing. Specifically, the need for timely processing of data that arrives at high rates creates a challenge for the traditional cloud computing paradigm, where data collected at various sources is sent to the cloud for processing. As an approach to this challenge, processing algorithms and infrastructure are distributed from the cloud to multiple tiers of computing, closer to the sources of data. This creates a wide range of devices for algorithms to be deployed on and software designs to adapt to.In this thesis, we investigate how hardware-aware algorithm designs on a variety of platforms lead to algorithm implementations that efficiently utilize the underlying resources. We design, implement and evaluate new techniques for representative applications that involve the whole spectrum of devices, from resource-constrained sensors in the field, to highly parallel servers. At each tier of processing capability, we identify key architectural features that are relevant for applications and propose designs that make use of these features to achieve high-rate, timely and energy-efficient processing.In the first part of the thesis, we focus on high-end servers and utilize two main approaches to achieve high throughput processing: vectorization and thread parallelism. We employ vectorization for the case of pattern matching algorithms used in security applications. We show that re-thinking the design of algorithms to better utilize the resources available in the platforms they are deployed on, such as vector processing units, can bring significant speedups in processing throughout. We then show how thread-aware data distribution and proper inter-thread synchronization allow scalability, especially for the problem of high-rate network traffic monitoring. We design a parallelization scheme for sketch-based algorithms that summarize traffic information, which allows them to handle incoming data at high rates and be able to answer queries on that data efficiently, without overheads.In the second part of the thesis, we target the intermediate tier of computing devices and focus on the typical examples of hardware that is found there. We show how single-board computers with embedded accelerators can be used to handle the computationally heavy part of applications and showcase it specifically for pattern matching for security-related processing. We further identify key hardware features that affect the performance of pattern matching algorithms on such devices, present a co-evaluation framework to compare algorithms, and design a new algorithm that efficiently utilizes the hardware features.In the last part of the thesis, we shift the focus to the low-power, resource-constrained tier of processing devices. We target wireless sensor networks and study distributed data processing algorithms where the processing happens on the same devices that generate the data. Specifically, we focus on a continuous monitoring algorithm (geometric monitoring) that aims to minimize communication between nodes. By deploying that algorithm in action, under realistic environments, we demonstrate that the interplay between the network protocol and the application plays an important role in this layer of devices. Based on that observation, we co-design a continuous monitoring application with a modern network stack and augment it further with an in-network aggregation technique. In this way, we show that awareness of the underlying network stack is important to realize the full potential of the continuous monitoring algorithm.The techniques and solutions presented in this thesis contribute to better utilization of hardware characteristics, across a wide spectrum of platforms. We employ these techniques on problems that are representative examples of current and upcoming applications and contribute with an outlook of emerging possibilities that can build on the results of the thesis

Doctor of Philosophy

dissertationStochastic methods, dense free-form mapping, atlas construction, and total variation are examples of advanced image processing techniques which are robust but computationally demanding. These algorithms often require a large amount of computational power as well as massive memory bandwidth. These requirements used to be ful lled only by supercomputers. The development of heterogeneous parallel subsystems and computation-specialized devices such as Graphic Processing Units (GPUs) has brought the requisite power to commodity hardware, opening up opportunities for scientists to experiment and evaluate the in uence of these techniques on their research and practical applications. However, harnessing the processing power from modern hardware is challenging. The di fferences between multicore parallel processing systems and conventional models are signi ficant, often requiring algorithms and data structures to be redesigned signi ficantly for efficiency. It also demands in-depth knowledge about modern hardware architectures to optimize these implementations, sometimes on a per-architecture basis. The goal of this dissertation is to introduce a solution for this problem based on a 3D image processing framework, using high performance APIs at the core level to utilize parallel processing power of the GPUs. The design of the framework facilitates an efficient application development process, which does not require scientists to have extensive knowledge about GPU systems, and encourages them to harness this power to solve their computationally challenging problems. To present the development of this framework, four main problems are described, and the solutions are discussed and evaluated: (1) essential components of a general 3D image processing library: data structures and algorithms, as well as how to implement these building blocks on the GPU architecture for optimal performance; (2) an implementation of unbiased atlas construction algorithms|an illustration of how to solve a highly complex and computationally expensive algorithm using this framework; (3) an extension of the framework to account for geometry descriptors to solve registration challenges with large scale shape changes and high intensity-contrast di fferences; and (4) an out-of-core streaming model, which enables developers to implement multi-image processing techniques on commodity hardware

Performance measurement and analysis of PC based cluster server using SET of Architecture and modeling a scalable High performance cluster

Not availabl

The role of parallel computing in bioinformatics

The need to intelligibly capture, manage and analyse the ever-increasing amount of publicly available genomic data is one of the challenges facing bioinformaticians today. Such analyses are in fact impractical using uniprocessor machines, which has led to an increasing reliance on clusters of commodity-priced computers. An existing network of cheap, commodity PCs was utilised as a single computational resource for parallel computing. The performance of the cluster was investigated using a whole genome-scanning program written in the Java programming language. The TSpaces framework, based on the Linda parallel programming model, was used to parallelise the application. Maximum speedup was achieved at between 30 and 50 processors, depending on the size of the genome being scanned. Together with this, the associated significant reductions in wall-clock time suggest that both parallel computing and Java have a significant role to play in the field of bioinformatics