Parallel implementation of 3D protein structure similarity searches using a GPU and the CUDA

Searching for similar 3D protein structures is one of the primary processes employed in the field of structural bioinformatics. However, the computational complexity of this process means that it is constantly necessary to search for new methods that can perform such a process faster and more efficiently. Finding molecular substructures that complex protein structures have in common is still a challenging task, especially when entire databases containing tens or even hundreds of thousands of protein structures must be scanned. Graphics processing units (GPUs) and general purpose graphics processing units (GPGPUs) can perform many time-consuming and computationally demanding processes much more quickly than a classical CPU can. In this paper, we describe the GPU-based implementation of the CASSERT algorithm for 3D protein structure similarity searching. This algorithm is based on the two-phase alignment of protein structures when matching fragments of the compared proteins. The GPU (GeForce GTX 560Ti: 384 cores, 2GB RAM) implementation of CASSERT (“GPU-CASSERT”) parallelizes both alignment phases and yields an average 180-fold increase in speed over its CPU-based, single-core implementation on an Intel Xeon E5620 (2.40GHz, 4 cores). In this paper, we show that massive parallelization of the 3D structure similarity search process on many-core GPU devices can reduce the execution time of the process, allowing it to be performed in real time. GPU-CASSERT is available at: http://zti.polsl.pl/dmrozek/science/gpucassert/cassert.htm.     

Scalable and highly parallel implementation of Smith-Waterman on graphics processing unit using CUDA

Program development environments have enabled graphics processing units (GPUs) to become an attractive high performance computing platform for the scientific community. A commonly posed problem in computational biology is protein database searching for functional similarities. The most accurate algorithm for sequence alignments is Smith-Waterman (SW). However, due to its computational complexity and rapidly increasing database sizes, the process becomes more and more time consuming making cluster based systems more desirable. Therefore, scalable and highly parallel methods are necessary to make SW a viable solution for life science researchers. In this paper we evaluate how SW fits onto the target GPU architecture by exploring ways to map the program architecture on the processor architecture. We develop new techniques to reduce the memory footprint of the application while exploiting the memory hierarchy of the GPU. With this implementation, GSW, we overcome the on chip memory size constraint, achieving 23× speedup compared to a serial implementation. Results show that as the query length increases our speedup almost stays stable indicating the solid scalability of our approach. Additionally this is a first of a kind implementation which purely runs on the GPU instead of a CPU-GPU integrated environment, making our design suitable for porting onto a cluster of GPUs.     

PSimScan: Algorithm and Utility for Fast Protein Similarity Search

In the era of metagenomics and diagnostics sequencing, the importance of protein comparison methods of boosted performance cannot be overstated. Here we present PSimScan (Protein Similarity Scanner), a flexible open source protein similarity search tool which provides a significant gain in speed compared to BLASTP at the price of controlled sensitivity loss. The PSimScan algorithm introduces a number of novel performance optimization methods that can be further used by the community to improve the speed and lower hardware requirements of bioinformatics software. The optimization starts at the lookup table construction, then the initial lookup table–based hits are passed through a pipeline of filtering and aggregation routines of increasing computational complexity. The first step in this pipeline is a novel algorithm that builds and selects ‘similarity zones’ aggregated from neighboring matches on small arrays of adjacent diagonals. PSimScan performs 5 to 100 times faster than the standard NCBI BLASTP, depending on chosen parameters, and runs on commodity hardware. Its sensitivity and selectivity at the slowest settings are comparable to the NCBI BLASTP’s and decrease with the increase of speed, yet stay at the levels reasonable for many tasks. PSimScan is most advantageous when used on large collections of query sequences. Comparing the entire proteome of Streptocuccus pneumoniae (2,042 proteins) to the NCBI’s non-redundant protein database of 16,971,855 records takes 6.5 hours on a moderately powerful PC, while the same task with the NCBI BLASTP takes over 66 hours. We describe innovations in the PSimScan algorithm in considerable detail to encourage bioinformaticians to improve on the tool and to use the innovations in their own software development.     

Democratic population decisions result in robust policy-gradient learning: a parametric study with GPU simulations

High performance computing on the Graphics Processing Unit (GPU) is an emerging field driven by the promise of high computational power at a low cost. However, GPU programming is a non-trivial task and moreover architectural limitations raise the question of whether investing effort in this direction may be worthwhile. In this work, we use GPU programming to simulate a two-layer network of Integrate-and-Fire neurons with varying degrees of recurrent connectivity and investigate its ability to learn a simplified navigation task using a policy-gradient learning rule stemming from Reinforcement Learning. The purpose of this paper is twofold. First, we want to support the use of GPUs in the field of Computational Neuroscience. Second, using GPU computing power, we investigate the conditions under which the said architecture and learning rule demonstrate best performance. Our work indicates that networks featuring strong Mexican-Hat-shaped recurrent connections in the top layer, where decision making is governed by the formation of a stable activity bump in the neural population (a "non-democratic" mechanism), achieve mediocre learning results at best. In absence of recurrent connections, where all neurons "vote" independently ("democratic") for a decision via population vector readout, the task is generally learned better and more robustly. Our study would have been extremely difficult on a desktop computer without the use of GPU programming. We present the routines developed for this purpose and show that a speed improvement of 5x up to 42x is provided versus optimised Python code. The higher speed is achieved when we exploit the parallelism of the GPU in the search of learning parameters. This suggests that efficient GPU programming can significantly reduce the time needed for simulating networks of spiking neurons, particularly when multiple parameter configurations are investigated.     

Fast parallel tandem mass spectral library searching using GPU hardware acceleration

Mass spectrometry-based proteomics is a maturing discipline of biologic research that is experiencing substantial growth. Instrumentation has steadily improved over time with the advent of faster and more sensitive instruments collecting ever larger data files. Consequently, the computational process of matching a peptide fragmentation pattern to its sequence, traditionally accomplished by sequence database searching and more recently also by spectral library searching, has become a bottleneck in many mass spectrometry experiments. In both of these methods, the main rate-limiting step is the comparison of an acquired spectrum with all potential matches from a spectral library or sequence database. This is a highly parallelizable process because the core computational element can be represented as a simple but arithmetically intense multiplication of two vectors. In this paper, we present a proof of concept project taking advantage of the massively parallel computing available on graphics processing units (GPUs) to distribute and accelerate the process of spectral assignment using spectral library searching. This program, which we have named FastPaSS (for Fast Parallelized Spectral Searching), is implemented in CUDA (Compute Unified Device Architecture) from NVIDIA, which allows direct access to the processors in an NVIDIA GPU. Our efforts demonstrate the feasibility of GPU computing for spectral assignment, through implementation of the validated spectral searching algorithm SpectraST in the CUDA environment.     

Computational approaches to study the effects of small genomic variations

Advances in DNA sequencing technologies have led to an avalanche-like increase in the number of gene sequences deposited in public databases over the last decade as well as the detection of an enormous number of previously unseen nucleotide variants therein. Given the size and complex nature of the genome-wide sequence variation data, as well as the rate of data generation, experimental characterization of the disease association of each of these variations or their effects on protein structure/function would be costly, laborious, time-consuming, and essentially impossible. Thus, in silico methods to predict the functional effects of sequence variations are constantly being developed. In this review, we summarize the major computational approaches and tools that are aimed at the prediction of the functional effect of mutations, and describe the state-of-the-art databases that can be used to obtain information about mutation significance. We also discuss future directions in this highly competitive field.     

SW#db: GPU-Accelerated Exact Sequence Similarity Database Search

In recent years we have witnessed a growth in sequencing yield, the number of samples sequenced, and as a result–the growth of publicly maintained sequence databases. The increase of data present all around has put high requirements on protein similarity search algorithms with two ever-opposite goals: how to keep the running times acceptable while maintaining a high-enough level of sensitivity. The most time consuming step of similarity search are the local alignments between query and database sequences. This step is usually performed using exact local alignment algorithms such as Smith-Waterman. Due to its quadratic time complexity, alignments of a query to the whole database are usually too slow. Therefore, the majority of the protein similarity search methods prior to doing the exact local alignment apply heuristics to reduce the number of possible candidate sequences in the database. However, there is still a need for the alignment of a query sequence to a reduced database. In this paper we present the SW#db tool and a library for fast exact similarity search. Although its running times, as a standalone tool, are comparable to the running times of BLAST, it is primarily intended to be used for exact local alignment phase in which the database of sequences has already been reduced. It uses both GPU and CPU parallelization and was 4–5 times faster than SSEARCH, 6–25 times faster than CUDASW++ and more than 20 times faster than SSW at the time of writing, using multiple queries on Swiss-prot and Uniref90 databases     

Network-based auto-probit modeling for protein function prediction

Predicting the functional roles of proteins based on various genome-wide data, such as protein-protein association networks, has become a canonical problem in computational biology. Approaching this task as a binary classification problem, we develop a network-based extension of the spatial auto-probit model. In particular, we develop a hierarchical Bayesian probit-based framework for modeling binary network-indexed processes, with a latent multivariate conditional autoregressive Gaussian process. The latter allows for the easy incorporation of protein-protein association network topologies-either binary or weighted-in modeling protein functional similarity. We use this framework to predict protein functions, for functions defined as terms in the Gene Ontology (GO) database, a popular rigorous vocabulary for biological functionality. Furthermore, we show how a natural extension of this framework can be used to model and correct for the high percentage of false negative labels in training data derived from GO, a serious shortcoming endemic to biological databases of this type. Our method performance is evaluated and compared with standard algorithms on weighted yeast protein-protein association networks, extracted from a recently developed integrative database called Search Tool for the Retrieval of INteracting Genes/proteins (STRING). Results show that our basic method is competitive with these other methods, and that the extended method-incorporating the uncertainty in negative labels among the training data-can yield nontrivial improvements in predictive accuracy.     

Similarity (<Emphasis Type="Italic">range</Emphasis> and <Emphasis Type="Italic">k</Emphasis>NN) queries processing on an Intel Xeon Phi coprocessor

Nowadays, the evolution of information technologies requires fast similarity search tools for analyzing new data types as audio, video, or images. The usual search by keys or records is not possible and to search on these databases is a compute-intensive problem. Regarding this, in the latest years, compute-intensive coprocessors (mainly NVIDIA GPUs) have been studied as a tool for accelerating sequential processing algorithms. In this work, we implement kNN and range queries on the recently launched Intel Xeon Phi coprocessor. We developed exhaustive and also indexing algorithms using the LC index. This index has been widely studied in sequential computing to accelerate similarity search on multimedia databases. We implement and compare different exhaustive and indexing versions showing some key factors in Xeon Phi to deal with this type of search. For indexing algorithms, we used a strategy based on cluster distribution among cores LC MIC Dist-C obtaining up to 168\(\times \) over the sequential exhaustive algorithm. Our algorithms using exhaustive strategies in Xeon Phi for range queries achieve up to 22\(\times \) speed-up over the sequential counterpart compared to the 12\(\times \) of a 20-core machine, and a similar advantage is achieved for kNN queries. Comparing with GPUs, we obtain higher performance on our indexing algorithms on Intel Xeon Phi. However, GPU works faster with memory-aligned access exhaustive algorithms. Our exhaustive approaches on Xeon Phi can be used on a wide class of databases, for example, non-metric spaces. Finally, we extend our algorithms to be used with large databases that do not fit in the coprocessor memory, showing a good scalability with the number of elements.     

Assessing protein similarity with Gene Ontology and its use in subnuclear localization prediction

Background  

The accomplishment of the various genome sequencing projects resulted in accumulation of massive amount of gene sequence information. This calls for a large-scale computational method for predicting protein localization from sequence. The protein localization can provide valuable information about its molecular function, as well as the biological pathway in which it participates. The prediction of localization of a protein at subnuclear level is a challenging task. In our previous work we proposed an SVM-based system using protein sequence information for this prediction task. In this work, we assess protein similarity with Gene Ontology (GO) and then improve the performance of the system by adding a module of nearest neighbor classifier using a similarity measure derived from the GO annotation terms for protein sequences.     

Columba: an integrated database of proteins,structures, and annotations

Background  

Structural and functional research often requires the computation of sets of protein structures based on certain properties of the proteins, such as sequence features, fold classification, or functional annotation. Compiling such sets using current web resources is tedious because the necessary data are spread over many different databases. To facilitate this task, we have created COLUMBA, an integrated database of annotations of protein structures.     

Predicting protein folding rate from amino acid sequence

Predicting protein folding rate from amino acid sequence is an important challenge in computational and molecular biology. Over the past few years, many methods have been developed to reflect the correlation between the folding rates and protein structures and sequences. In this paper, we present an effective method, a combined neural network--genetic algorithm approach, to predict protein folding rates only from amino acid sequences, without any explicit structural information. The originality of this paper is that, for the first time, it tackles the effect of sequence order. The proposed method provides a good correlation between the predicted and experimental folding rates. The correlation coefficient is 0.80 and the standard error is 2.65 for 93 proteins, the largest such databases of proteins yet studied, when evaluated with leave-one-out jackknife test. The comparative results demonstrate that this correlation is better than most of other methods, and suggest the important contribution of sequence order information to the determination of protein folding rates.     

AutoSCOP: automated prediction of SCOP classifications using unique pattern-class mappings

MOTIVATION: The sequence patterns contained in the available motif and hidden Markov model (HMM) databases are a valuable source of information for protein sequence annotation. For structure prediction and fold recognition purposes, we computed mappings from such pattern databases to the protein domain hierarchy given by the ASTRAL compendium and applied them to the prediction of SCOP classifications. Our aim is to make highly confident predictions also for non-trivial cases if possible and abstain from a prediction otherwise, and thus to provide a method that can be used as a first step in a pipeline of prediction methods. We describe two successful examples for such pipelines. With the AutoSCOP approach, it is possible to make predictions in a large-scale manner for many domains of the available sequences in the well-known protein sequence databases. RESULTS: AutoSCOP computes unique sequence patterns and pattern combinations for SCOP classifications. For instance, we assign a SCOP superfamily to a pattern found in its members whenever the pattern does not occur in any other SCOP superfamily. Especially on the fold and superfamily level, our method achieves both high sensitivity (above 93%) and high specificity (above 98%) on the difference set between two ASTRAL versions, due to being able to abstain from unreliable predictions. Further, on a harder test set filtered at low sequence identity, the combination with profile-profile alignments improves accuracy and performs comparably even to structure alignment methods. Integrating our method with structure alignment, we are able to achieve an accuracy of 99% on SCOP fold classifications on this set. In an analysis of false assignments of domains from new folds/superfamilies/families to existing SCOP classifications, AutoSCOP correctly abstains for more than 70% of the domains belonging to new folds and superfamilies, and more than 80% of the domains belonging to new families. These findings show that our approach is a useful additional filter for SCOP classification prediction of protein domains in combination with well-known methods such as profile-profile alignment. AVAILABILITY: A web server where users can input their domain sequences is available at http://www.bio.ifi.lmu.de/autoscop.     

Fast Acceleration of 2D Wave Propagation Simulations Using Modern Computational Accelerators

Recent developments in modern computational accelerators like Graphics Processing Units (GPUs) and coprocessors provide great opportunities for making scientific applications run faster than ever before. However, efficient parallelization of scientific code using new programming tools like CUDA requires a high level of expertise that is not available to many scientists. This, plus the fact that parallelized code is usually not portable to different architectures, creates major challenges for exploiting the full capabilities of modern computational accelerators. In this work, we sought to overcome these challenges by studying how to achieve both automated parallelization using OpenACC and enhanced portability using OpenCL. We applied our parallelization schemes using GPUs as well as Intel Many Integrated Core (MIC) coprocessor to reduce the run time of wave propagation simulations. We used a well-established 2D cardiac action potential model as a specific case-study. To the best of our knowledge, we are the first to study auto-parallelization of 2D cardiac wave propagation simulations using OpenACC. Our results identify several approaches that provide substantial speedups. The OpenACC-generated GPU code achieved more than speedup above the sequential implementation and required the addition of only a few OpenACC pragmas to the code. An OpenCL implementation provided speedups on GPUs of at least faster than the sequential implementation and faster than a parallelized OpenMP implementation. An implementation of OpenMP on Intel MIC coprocessor provided speedups of with only a few code changes to the sequential implementation. We highlight that OpenACC provides an automatic, efficient, and portable approach to achieve parallelization of 2D cardiac wave simulations on GPUs. Our approach of using OpenACC, OpenCL, and OpenMP to parallelize this particular model on modern computational accelerators should be applicable to other computational models of wave propagation in multi-dimensional media.     

Pathogen proteins eliciting antibodies do not share epitopes with host proteins: a bioinformatics approach

The best way to prevent diseases caused by pathogens is by the use of vaccines. The advent of genomics enables genome-wide searches of new vaccine candidates, called reverse vaccinology. The most common strategy to apply reverse vaccinology is by designing subunit recombinant vaccines, which usually generate an humoral immune response due to B-cell epitopes in proteins. A major problem for this strategy is the identification of protective immunogenic proteins from the surfome of the pathogen. Epitope mimicry may lead to auto-immune phenomena related to several human diseases. A sequence-based computational analysis has been carried out applying the BLASTP algorithm. Therefore, two huge databases have been created, one with the most complete and current linear B-cell epitopes, and the other one with the surface-protein sequences of the main human respiratory bacterial pathogens. We found that none of the 7353 linear B-cell epitopes analysed shares any sequence identity region with human proteins capable of generating antibodies, and that only 1% of the 2175 exposed proteins analysed contain a stretch of shared sequence with the human proteome. These findings suggest the existence of a mechanism to avoid autoimmunity. We also propose a strategy for corroborating or warning about the viability of a protein linear B-cell epitope as a putative vaccine candidate in a reverse vaccinology study; so, epitopes without any sequence identity with human proteins should be very good vaccine candidates, and the other way around.     

Patient-specific modelling of pulmonary airflow using GPU cluster for the application in medical practice

In this paper, we propose a novel patient-specific method of modelling pulmonary airflow using graphics processing unit (GPU) computation that can be applied in medical practice. To overcome the barriers imposed by computation speed, installation price and footprint to the application of computational fluid dynamics, we focused on GPU computation and the lattice Boltzmann method (LBM). The GPU computation and LBM are compatible due to the characteristics of the GPU. As the optimisation of data access is essential for the performance of the GPU computation, we developed an adaptive meshing method, in which an airway model is covered by isotropic subdomains consisting of a uniform Cartesian mesh. We found that 4(3) size subdomains gave the best performance. The code was also tested on a small GPU cluster to confirm its performance and applicability, as the price and footprint are reasonable for medical applications.