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

Evolutionary genomics : statistical and computational methods

This open access book addresses the challenge of analyzing and understanding the evolutionary dynamics of complex biological systems at the genomic level, and elaborates on some promising strategies that would bring us closer to uncovering of the vital relationships between genotype and phenotype. After a few educational primers, the book continues with sections on sequence homology and alignment, phylogenetic methods to study genome evolution, methodologies for evaluating selective pressures on genomic sequences as well as genomic evolution in light of protein domain architecture and transposable elements, population genomics and other omics, and discussions of current bottlenecks in handling and analyzing genomic data. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of detail and expert implementation advice that lead to the best results. Authoritative and comprehensive, Evolutionary Genomics: Statistical and Computational Methods, Second Edition aims to serve both novices in biology with strong statistics and computational skills, and molecular biologists with a good grasp of standard mathematical concepts, in moving this important field of study forward

Evolutionary Genomics

This open access book addresses the challenge of analyzing and understanding the evolutionary dynamics of complex biological systems at the genomic level, and elaborates on some promising strategies that would bring us closer to uncovering of the vital relationships between genotype and phenotype. After a few educational primers, the book continues with sections on sequence homology and alignment, phylogenetic methods to study genome evolution, methodologies for evaluating selective pressures on genomic sequences as well as genomic evolution in light of protein domain architecture and transposable elements, population genomics and other omics, and discussions of current bottlenecks in handling and analyzing genomic data. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of detail and expert implementation advice that lead to the best results. Authoritative and comprehensive, Evolutionary Genomics: Statistical and Computational Methods, Second Edition aims to serve both novices in biology with strong statistics and computational skills, and molecular biologists with a good grasp of standard mathematical concepts, in moving this important field of study forward

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

Proceedings, MSVSCC 2016

Proceedings of the 10th Annual Modeling, Simulation & Visualization Student Capstone Conference held on April 14, 2016 at VMASC in Suffolk, Virginia

Models for Parallel Computation in Multi-Core, Heterogeneous, and Ultra Wide-Word Architectures

Multi-core processors have become the dominant processor architecture with 2, 4, and 8 cores on a chip being widely available and an increasing number of cores predicted for the future. In addition, the decreasing costs and increasing programmability of Graphic Processing Units (GPUs) have made these an accessible source of parallel processing power in general purpose computing. Among the many research challenges that this scenario has raised are the fundamental problems related to theoretical modeling of computation in these architectures. In this thesis we study several aspects of computation in modern parallel architectures, from modeling of computation in multi-cores and heterogeneous platforms, to multi-core cache management strategies, through the proposal of an architecture that exploits bit-parallelism on thousands of bits. Observing that in practice multi-cores have a small number of cores, we propose a model for low-degree parallelism for these architectures. We argue that assuming a small number of processors (logarithmic in a problem's input size) simplifies the design of parallel algorithms. We show that in this model a large class of divide-and-conquer and dynamic programming algorithms can be parallelized with simple modifications to sequential programs, while achieving optimal parallel speedups. We further explore low-degree-parallelism in computation, providing evidence of fundamental differences in practice and theory between systems with a sublinear and linear number of processors, and suggesting a sharp theoretical gap between the classes of problems that are efficiently parallelizable in each case. Efficient strategies to manage shared caches play a crucial role in multi-core performance. We propose a model for paging in multi-core shared caches, which extends classical paging to a setting in which several threads share the cache. We show that in this setting traditional cache management policies perform poorly, and that any effective strategy must partition the cache among threads, with a partition that adapts dynamically to the demands of each thread. Inspired by the shared cache setting, we introduce the minimum cache usage problem, an extension to classical sequential paging in which algorithms must account for the amount of cache they use. This cache-aware model seeks algorithms with good performance in terms of faults and the amount of cache used, and has applications in energy efficient caching and in shared cache scenarios. The wide availability of GPUs has added to the parallel power of multi-cores, however, most applications underutilize the available resources. We propose a model for hybrid computation in heterogeneous systems with multi-cores and GPU, and describe strategies for generic parallelization and efficient scheduling of a large class of divide-and-conquer algorithms. Lastly, we introduce the Ultra-Wide Word architecture and model, an extension of the word-RAM model, that allows for constant time operations on thousands of bits in parallel. We show that a large class of existing algorithms can be implemented in the Ultra-Wide Word model, achieving speedups comparable to those of multi-threaded computations, while avoiding the more difficult aspects of parallel programming

Efficient approximate string matching techniques for sequence alignment

One of the outstanding milestones achieved in recent years in the field of biotechnology research has been the development of high-throughput sequencing (HTS). Due to the fact that at the moment it is technically impossible to decode the genome as a whole, HTS technologies read billions of relatively short chunks of a genome at random locations. Such reads then need to be located within a reference for the species being studied (that is aligned or mapped to the genome): for each read one identifies in the reference regions that share a large sequence similarity with it, therefore indicating what the read¿s point or points of origin may be. HTS technologies are able to re-sequence a human individual (i.e. to establish the differences between his/her individual genome and the reference genome for the human species) in a very short period of time. They have also paved the way for the development of a number of new protocols and methods, leading to novel insights in genomics and biology in general. However, HTS technologies also pose a challenge to traditional data analysis methods; this is due to the sheer amount of data to be processed and the need for improved alignment algorithms that can generate accurate results quickly. This thesis tackles the problem of sequence alignment as a step within the analysis of HTS data. Its contributions focus on both the methodological aspects and the algorithmic challenges towards efficient, scalable, and accurate HTS mapping. From a methodological standpoint, this thesis strives to establish a comprehensive framework able to assess the quality of HTS mapping results. In order to be able to do so one has to understand the source and nature of mapping conflicts, and explore the accuracy limits inherent in how sequence alignment is performed for current HTS technologies. From an algorithmic standpoint, this work introduces state-of-the-art index structures and approximate string matching algorithms. They contribute novel insights that can be used in practical applications towards efficient and accurate read mapping. More in detail, first we present methods able to reduce the storage space taken by indexes for genome-scale references, while still providing fast query access in order to support effective search algorithms. Second, we describe novel filtering techniques that vastly reduce the computational requirements of sequence mapping, but are nonetheless capable of giving strict algorithmic guarantees on the completeness of the results. Finally, this thesis presents new incremental algorithmic techniques able to combine several approximate string matching algorithms; this leads to efficient and flexible search algorithms allowing the user to reach arbitrary search depths. All algorithms and methodological contributions of this thesis have been implemented as components of a production aligner, the GEM-mapper, which is publicly available, widely used worldwide and cited by a sizeable body of literature. It offers flexible and accurate sequence mapping while outperforming other HTS mappers both as to running time and to the quality of the results it produces.Uno de los avances más importantes de los últimos años en el campo de la biotecnología ha sido el desarrollo de las llamadas técnicas de secuenciación de alto rendimiento (high-throughput sequencing, HTS). Debido a las limitaciones técnicas para secuenciar un genoma, las técnicas de alto rendimiento secuencian individualmente billones de pequeñas partes del genoma provenientes de regiones aleatorias. Posteriormente, estas pequeñas secuencias han de ser localizadas en el genoma de referencia del organismo en cuestión. Este proceso se denomina alineamiento - o mapeado - y consiste en identificar aquellas regiones del genoma de referencia que comparten una alta similaridad con las lecturas producidas por el secuenciador. De esta manera, en cuestión de horas, la secuenciación de alto rendimiento puede secuenciar un individuo y establecer las diferencias de este con el resto de la especie. En última instancia, estas tecnologías han potenciado nuevos protocolos y metodologías de investigación con un profundo impacto en el campo de la genómica, la medicina y la biología en general. La secuenciación alto rendimiento, sin embargo, supone un reto para los procesos tradicionales de análisis de datos. Debido a la elevada cantidad de datos a analizar, se necesitan nuevas y mejoradas técnicas algorítmicas que puedan escalar con el volumen de datos y producir resultados precisos. Esta tesis aborda dicho problema. Las contribuciones que en ella se realizan se enfocan desde una perspectiva metodológica y otra algorítmica que propone el desarrollo de nuevos algoritmos y técnicas que permitan alinear secuencias de manera eficiente, precisa y escalable. Desde el punto de vista metodológico, esta tesis analiza y propone un marco de referencia para evaluar la calidad de los resultados del alineamiento de secuencias. Para ello, se analiza el origen de los conflictos durante la alineación de secuencias y se exploran los límites alcanzables en calidad con las tecnologías de secuenciación de alto rendimiento. Desde el punto de vista algorítmico, en el contexto de la búsqueda aproximada de patrones, esta tesis propone nuevas técnicas algorítmicas y de diseño de índices con el objetivo de mejorar la calidad y el desempeño de las herramientas dedicadas a alinear secuencias. En concreto, esta tesis presenta técnicas de diseño de índices genómicos enfocados a obtener un acceso más eficiente y escalable. También se presentan nuevas técnicas algorítmicas de filtrado con el fin de reducir el tiempo de ejecución necesario para alinear secuencias. Y, por último, se proponen algoritmos incrementales y técnicas híbridas para combinar métodos de alineamiento y mejorar el rendimiento en búsquedas donde el error esperado es alto. Todo ello sin degradar la calidad de los resultados y con garantías formales de precisión. Para concluir, es preciso apuntar que todos los algoritmos y metodologías propuestos en esta tesis están implementados y forman parte del alineador GEM. Este versátil alineador ofrece resultados de alta calidad en entornos de producción siendo varias veces más rápido que otros alineadores. En la actualidad este software se ofrece gratuitamente, tiene una amplia comunidad de usuarios y ha sido citado en numerosas publicaciones científicas

Road Information Extraction from Mobile LiDAR Point Clouds using Deep Neural Networks

Urban roads, as one of the essential transportation infrastructures, provide considerable motivations for rapid urban sprawl and bring notable economic and social benefits. Accurate and efficient extraction of road information plays a significant role in the development of autonomous vehicles (AVs) and high-definition (HD) maps. Mobile laser scanning (MLS) systems have been widely used for many transportation-related studies and applications in road inventory, including road object detection, pavement inspection, road marking segmentation and classification, and road boundary extraction, benefiting from their large-scale data coverage, high surveying flexibility, high measurement accuracy, and reduced weather sensitivity. Road information from MLS point clouds is significant for road infrastructure planning and maintenance, and have an important impact on transportation-related policymaking, driving behaviour regulation, and traffic efficiency enhancement. Compared to the existing threshold-based and rule-based road information extraction methods, deep learning methods have demonstrated superior performance in 3D road object segmentation and classification tasks. However, three main challenges remain that impede deep learning methods for precisely and robustly extracting road information from MLS point clouds. (1) Point clouds obtained from MLS systems are always in large-volume and irregular formats, which has presented significant challenges for managing and processing such massive unstructured points. (2) Variations in point density and intensity are inevitable because of the profiling scanning mechanism of MLS systems. (3) Due to occlusions and the limited scanning range of onboard sensors, some road objects are incomplete, which considerably degrades the performance of threshold-based methods to extract road information. To deal with these challenges, this doctoral thesis proposes several deep neural networks that encode inherent point cloud features and extract road information. These novel deep learning models have been tested by several datasets to deliver robust and accurate road information extraction results compared to state-of-the-art deep learning methods in complex urban environments. First, an end-to-end feature extraction framework for 3D point cloud segmentation is proposed using dynamic point-wise convolutional operations at multiple scales. This framework is less sensitive to data distribution and computational power. Second, a capsule-based deep learning framework to extract and classify road markings is developed to update road information and support HD maps. It demonstrates the practical application of combining capsule networks with hierarchical feature encodings of georeferenced feature images. Third, a novel deep learning framework for road boundary completion is developed using MLS point clouds and satellite imagery, based on the U-shaped network and the conditional deep convolutional generative adversarial network (c-DCGAN). Empirical evidence obtained from experiments compared with state-of-the-art methods demonstrates the superior performance of the proposed models in road object semantic segmentation, road marking extraction and classification, and road boundary completion tasks

EG-ICE 2021 Workshop on Intelligent Computing in Engineering

The 28th EG-ICE International Workshop 2021 brings together international experts working at the interface between advanced computing and modern engineering challenges. Many engineering tasks require open-world resolutions to support multi-actor collaboration, coping with approximate models, providing effective engineer-computer interaction, search in multi-dimensional solution spaces, accommodating uncertainty, including specialist domain knowledge, performing sensor-data interpretation and dealing with incomplete knowledge. While results from computer science provide much initial support for resolution, adaptation is unavoidable and most importantly, feedback from addressing engineering challenges drives fundamental computer-science research. Competence and knowledge transfer goes both ways