Integrative multicellular biological modeling: a case study of 3D epidermal development using GPU algorithms

<p>Abstract</p> <p>Background</p> <p>Simulation of sophisticated biological models requires considerable computational power. These models typically integrate together numerous biological phenomena such as spatially-explicit heterogeneous cells, cell-cell interactions, cell-environment interactions and intracellular gene networks. The recent advent of programming for graphical processing units (GPU) opens up the possibility of developing more integrative, detailed and predictive biological models while at the same time decreasing the computational cost to simulate those models.</p> <p>Results</p> <p>We construct a 3D model of epidermal development and provide a set of GPU algorithms that executes significantly faster than sequential central processing unit (CPU) code. We provide a parallel implementation of the subcellular element method for individual cells residing in a lattice-free spatial environment. Each cell in our epidermal model includes an internal gene network, which integrates cellular interaction of Notch signaling together with environmental interaction of basement membrane adhesion, to specify cellular state and behaviors such as growth and division. We take a pedagogical approach to describing how modeling methods are efficiently implemented on the GPU including memory layout of data structures and functional decomposition. We discuss various programmatic issues and provide a set of design guidelines for GPU programming that are instructive to avoid common pitfalls as well as to extract performance from the GPU architecture.</p> <p>Conclusions</p> <p>We demonstrate that GPU algorithms represent a significant technological advance for the simulation of complex biological models. We further demonstrate with our epidermal model that the integration of multiple complex modeling methods for heterogeneous multicellular biological processes is both feasible and computationally tractable using this new technology. We hope that the provided algorithms and source code will be a starting point for modelers to develop their own GPU implementations, and encourage others to implement their modeling methods on the GPU and to make that code available to the wider community.</p

The feasibility of genome-scale biological network inference using Graphics Processing Units

Abstract Systems research spanning fields from biology to finance involves the identification of models to represent the underpinnings of complex systems. Formal approaches for data-driven identification of network interactions include statistical inference-based approaches and methods to identify dynamical systems models that are capable of fitting multivariate data. Availability of large data sets and so-called ‘big data’ applications in biology present great opportunities as well as major challenges for systems identification/reverse engineering applications. For example, both inverse identification and forward simulations of genome-scale gene regulatory network models pose compute-intensive problems. This issue is addressed here by combining the processing power of Graphics Processing Units (GPUs) and a parallel reverse engineering algorithm for inference of regulatory networks. It is shown that, given an appropriate data set, information on genome-scale networks (systems of 1000 or more state variables) can be inferred using a reverse-engineering algorithm in a matter of days on a small-scale modern GPU cluster.https://deepblue.lib.umich.edu/bitstream/2027.42/136186/1/13015_2017_Article_100.pd

Accelerating exact and approximate inference for (distributed) discrete optimization with GPUs

Discrete optimization is a central problem in artificial intelligence. The optimization of the aggregated cost of a network of cost functions arises in a variety of problems including Weighted Constraint Programs (WCSPs), Distributed Constraint Optimization (DCOP), as well as optimization in stochastic variants such as the tasks of finding the most probable explanation (MPE) in belief networks. Inference-based algorithms are powerful techniques for solving discrete optimization problems, which can be used independently or in combination with other techniques. However, their applicability is often limited by their compute intensive nature and their space requirements. This paper proposes the design and implementation of a novel inference-based technique, which exploits modern massively parallel architectures, such as those found in Graphical Processing Units (GPUs), to speed up the resolution of exact and approximated inference-based algorithms for discrete optimization. The paper studies the proposed algorithm in both centralized and distributed optimization contexts. The paper demonstrates that the use of GPUs provides significant advantages in terms of runtime and scalability, achieving up to two orders of magnitude in speedups and showing a considerable reduction in execution time (up to 345 times faster) with respect to a sequential version

Homology sequence analysis using GPU acceleration

A number of problems in bioinformatics, systems biology and computational biology field require abstracting physical entities to mathematical or computational models. In such studies, the computational paradigms often involve algorithms that can be solved by the Central Processing Unit (CPU). Historically, those algorithms benefit from the advancements of computing power in the serial processing capabilities of individual CPU cores. However, the growth has slowed down over recent years, as scaling out CPU has been shown to be both cost-prohibitive and insecure. To overcome this problem, parallel computing approaches that employ the Graphics Processing Unit (GPU) have gained attention as complementing or replacing traditional CPU approaches. The premise of this research is to investigate the applicability of various parallel computing platforms to several problems in the detection and analysis of homology in biological sequence. I hypothesize that by exploiting the sheer amount of computation power and sequencing data, it is possible to deduce information from raw sequences without supplying the underlying prior knowledge to come up with an answer. I have developed such tools to perform analysis at scales that are traditionally unattainable with general-purpose CPU platforms. I have developed a method to accelerate sequence alignment on the GPU, and I used the method to investigate whether the Operational Taxonomic Unit (OTU) classification problem can be improved with such sheer amount of computational power. I have developed a method to accelerate pairwise k-mer comparison on the GPU, and I used the method to further develop PolyHomology, a framework to scaffold shared sequence motifs across large numbers of genomes to illuminate the structure of the regulatory network in yeasts. The results suggest that such approach to heterogeneous computing could help to answer questions in biology and is a viable path to new discoveries in the present and the future.Includes bibliographical reference

Applications on emerging paradigms in parallel computing

The area of computing is seeing parallelism increasingly being incorporated at various levels: from the lowest levels of vector processing units following Single Instruction Multiple Data (SIMD) processing, Simultaneous Multi-threading (SMT) architectures, and multi/many-cores with thread-level shared memory and SIMT parallelism, to the higher levels of distributed memory parallelism as in supercomputers and clusters, and scaling them to large distributed systems as server farms and clouds. All together these form a large hierarchy of parallelism. Developing high-performance parallel algorithms and efficient software tools, which make use of the available parallelism, is inevitable in order to harness the raw computational power these emerging systems have to offer. In the work presented in this thesis, we develop architecture-aware parallel techniques on such emerging paradigms in parallel computing, specifically, parallelism offered by the emerging multi- and many-core architectures, as well as the emerging area of cloud computing, to target large scientific applications. First, we develop efficient parallel algorithms to compute optimal pairwise alignments of genomic sequences on heterogeneous multi-core processors, and demonstrate them on the IBM Cell Broadband Engine. Then, we develop parallel techniques for scheduling all-pairs computations on heterogeneous systems, including clusters of Cell processors, and NVIDIA graphics processors. We compare the performance of our strategies on Cell, GPU and Intel Nehalem multi-core processors. Further, we apply our algorithms to specific applications taken from the areas of systems biology, fluid dynamics and materials science: pairwise Mutual Information computations for reconstruction of gene regulatory networks; pairwise Lp-norm distance computations for coherent structures discovery in the design of flapping-wing Micro Air Vehicles, and construction of stochastic models for a set of properties of heterogeneous materials. Lastly, in the area of cloud computing, we propose and develop an abstract framework to enable computations in parallel on large tree structures, to facilitate easy development of a class of scientific applications based on trees. Our framework, in the style of Google\u27s MapReduce paradigm, is based on two generic user-defined functions through which a user writes an application. We implement our framework as a generic programming library for a large cluster of homogeneous multi-core processor, and demonstrate its applicability through two applications: all-k-nearest neighbors computations, and Fast Multipole Method (FMM) based simulations

Biomolecular Event Extraction using Natural Language Processing

Biomedical research and discoveries are communicated through scholarly publications and this literature is voluminous, rich in scientific text and growing exponentially by the day. Biomedical journals publish nearly three thousand research articles daily, making literature search a challenging proposition for researchers. Biomolecular events involve genes, proteins, metabolites, and enzymes that provide invaluable insights into biological processes and explain the physiological functional mechanisms. Text mining (TM) or extraction of such events automatically from big data is the only quick and viable solution to gather any useful information. Such events extracted from biological literature have a broad range of applications like database curation, ontology construction, semantic web search and interactive systems. However, automatic extraction has its challenges on account of ambiguity and the diverse nature of natural language and associated linguistic occurrences like speculations, negations etc., which commonly exist in biomedical texts and lead to erroneous elucidation. In the last decade, many strategies have been proposed in this field, using different paradigms like Biomedical natural language processing (BioNLP), machine learning and deep learning. Also, new parallel computing architectures like graphical processing units (GPU) have emerged as possible candidates to accelerate the event extraction pipeline. This paper reviews and provides a summarization of the key approaches in complex biomolecular big data event extraction tasks and recommends a balanced architecture in terms of accuracy, speed, computational cost, and memory usage towards developing a robust GPU-accelerated BioNLP system

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

Introducing deep learning -based methods into the variant calling analysis pipeline

Biological interpretation of the genetic variation enhances our understanding of normal and pathological phenotypes, and may lead to the development of new therapeutics. However, it is heavily dependent on the genomic data analysis, which might be inaccurate due to the various sequencing errors and inconsistencies caused by these errors. Modern analysis pipelines already utilize heuristic and statistical techniques, but the rate of falsely identified mutations remains high and variable, particular sequencing technology, settings and variant type. Recently, several tools based on deep neural networks have been published. The neural networks are supposed to find motifs in the data that were not previously seen. The performance of these novel tools is assessed in terms of precision and recall, as well as computational efficiency. Following the established best practices in both variant detection and benchmarking, the discussed tools demonstrate accuracy metrics and computational efficiency that spur further discussion