MR-CUDASW - GPU accelerated Smith-Waterman algorithm for medium-length (meta)genomic data

The idea of using a graphics processing unit (GPU) for more than simply graphic output purposes has been around for quite some time in scientific communities. However, it is only recently that its benefits for a range of bioinformatics and life sciences compute-intensive tasks has been recognized. This thesis investigates the possibility of improving the performance of the overlap determination stage of an Overlap Layout Consensus (OLC)-based assembler by using a GPU-based implementation of the Smith-Waterman algorithm. In this thesis an existing GPU-accelerated sequence alignment algorithm is adapted and expanded to reduce its completion time. A number of improvements and changes are made to the original software. Workload distribution, query profile construction, and thread scheduling techniques implemented by the original program are replaced by custom methods specifically designed to handle medium-length reads. Accordingly, this algorithm is the first highly parallel solution that has been specifically optimized to process medium-length nucleotide reads (DNA/RNA) from modern sequencing machines (i.e. Ion Torrent). Results show that the software reaches up to 82 GCUPS (Giga Cell Updates Per Second) on a single-GPU graphic card running on a commodity desktop hardware. As a result it is the fastest GPU-based implemen- tation of the Smith-Waterman algorithm tailored for processing medium-length nucleotide reads. Despite being designed for performing the Smith-Waterman algorithm on medium-length nucleotide sequences, this program also presents great potential for improving heterogeneous computing with CUDA-enabled GPUs in general and is expected to make contributions to other research problems that require sensitive pairwise alignment to be applied to a large number of reads. Our results show that it is possible to improve the performance of bioinformatics algorithms by taking full advantage of the compute resources of the underlying commodity hardware and further, these results are especially encouraging since GPU performance grows faster than multi-core CPUs

Proceedings of the First PhD Symposium on Sustainable Ultrascale Computing Systems (NESUS PhD 2016)

Proceedings of the First PhD Symposium on Sustainable Ultrascale Computing Systems (NESUS PhD 2016) Timisoara, Romania. February 8-11, 2016.The PhD Symposium was a very good opportunity for the young researchers to share information and knowledge, to present their current research, and to discuss topics with other students in order to look for synergies and common research topics. The idea was very successful and the assessment made by the PhD Student was very good. It also helped to achieve one of the major goals of the NESUS Action: to establish an open European research network targeting sustainable solutions for ultrascale computing aiming at cross fertilization among HPC, large scale distributed systems, and big data management, training, contributing to glue disparate researchers working across different areas and provide a meeting ground for researchers in these separate areas to exchange ideas, to identify synergies, and to pursue common activities in research topics such as sustainable software solutions (applications and system software stack), data management, energy efficiency, and resilience.European Cooperation in Science and Technology. COS

Using Context to Improve Network-based Exploit Kit Detection

Today, our computers are routinely compromised while performing seemingly innocuous activities like reading articles on trusted websites (e.g., the NY Times). These compromises are perpetrated via complex interactions involving the advertising networks that monetize these sites. Web-based compromises such as exploit kits are similar to any other scam -- the attacker wants to lure an unsuspecting client into a trap to steal private information, or resources -- generating 10s of millions of dollars annually. Exploit kits are web-based services specifically designed to capitalize on vulnerabilities in unsuspecting client computers in order to install malware without a user's knowledge. Sadly, it only takes a single successful infection to ruin a user's financial life, or lead to corporate breaches that result in millions of dollars of expense and loss of customer trust. Exploit kits use a myriad of techniques to obfuscate each attack instance, making current network-based defenses such as signature-based network intrusion detection systems far less effective than in years past. Dynamic analysis or honeyclient analysis on these exploits plays a key role in identifying new attacks for signature generation, but provides no means of inspecting end-user traffic on the network to identify attacks in real time. As a result, defenses designed to stop such malfeasance often arrive too late or not at all resulting in high false positive and false negative (error) rates. In order to deal with these drawbacks, three new detection approaches are presented. To deal with the issue of a high number of errors, a new technique for detecting exploit kit interactions on a network is proposed. The technique capitalizes on the fact that an exploit kit leads its potential victim through a process of exploitation by forcing the browser to download multiple web resources from malicious servers. This process has an inherent structure that can be captured in HTTP traffic and used to significantly reduce error rates. The approach organizes HTTP traffic into tree-like data structures, and, using a scalable index of exploit kit traces as samples, models the detection process as a subtree similarity search problem. The technique is evaluated on 3,800 hours of web traffic on a large enterprise network, and results show that it reduces false positive rates by four orders of magnitude over current state-of-the-art approaches. While utilizing structure can vastly improve detection rates over current approaches, it does not go far enough in helping defenders detect new, previously unseen attacks. As a result, a new framework that applies dynamic honeyclient analysis directly on network traffic at scale is proposed. The framework captures and stores a configurable window of reassembled HTTP objects network wide, uses lightweight content rendering to establish the chain of requests leading up to a suspicious event, then serves the initial response content back to the honeyclient in an isolated network. The framework is evaluated on a diverse collection of exploit kits as they evolve over a 1 year period. The empirical evaluation suggests that the approach offers significant operational value, and a single honeyclient can support a campus deployment of thousands of users. While the above approaches attempt to detect exploit kits before they have a chance to infect the client, they cannot protect a client that has already been infected. The final technique detects signs of post infection behavior by intrusions that abuses the domain name system (DNS) to make contact with an attacker. Contemporary detection approaches utilize the structure of a domain name and require hundreds of DNS messages to detect such malware. As a result, these detection mechanisms cannot detect malware in a timely manner and are susceptible to high error rates. The final technique, based on sequential hypothesis testing, uses the DNS message patterns of a subset of DNS traffic to detect malware in as little as four DNS messages, and with orders of magnitude reduction in error rates. The results of this work can make a significant operational impact on network security analysis, and open several exciting future directions for network security research.Doctor of Philosoph

The Immune Epitope Database and Analysis Resource Program 2003–2018: reflections and outlook

The Immune Epitope Database and Analysis Resource (IEDB) contains information related to antibodies and T cells across an expansive scope of research fields (infectious diseases, allergy, autoimmunity, and transplantation). Capture and representation of the data to reflect growing scientific standards and techniques have required continual refinement of our rigorous curation and query and reporting processes beginning with the automated classification of over 28 million PubMed abstracts, and resulting in easily searchable data from over 20,000 published manuscripts. Data related to MHC binding and elution, nonpeptidics, natural processing, receptors, and 3D structure is first captured through manual curation and subsequently maintained through recuration to reflect evolving scientific standards. Upon promotion to the free, public database, users can query and export records of specific relevance via the online web portal which undergoes iterative development to best enable efficient data access. In parallel, the companion Analysis Resource site hosts a variety of tools that assist in the bioinformatic analyses of epitopes and related structures, which can be applied to IEDB-derived and independent datasets alike. Available tools are classified into two categories: analysis and prediction. Analysis tools include epitope clustering, sequence conservancy, and more, while prediction tools cover T and B cell epitope binding, immunogenicity, and TCR/BCR structures. In addition to these tools, benchmarking servers which allow for unbiased performance comparison are also offered. In order to expand and support the user-base of both the database and Analysis Resource, the research team actively engages in community outreach through publication of ongoing work, conference attendance and presentations, hosting of user workshops, and the provision of online help. This review provides a description of the IEDB database infrastructure, curation and recuration processes, query and reporting capabilities, the Analysis Resource, and our Community Outreach efforts, including assessment of the impact of the IEDB across the research community.Fil: Martini, Sheridan. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Nielsen, Morten. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina. Technical University of Denmark; DinamarcaFil: Peters, Bjoern. La Jolla Institute for Allergy and Immunology; Estados Unidos. University of California at San Diego; Estados UnidosFil: Sette, Alessandro. La Jolla Institute for Allergy and Immunology; Estados Unidos. University of California at San Diego; Estados Unido

Machine-Learning-Enabled Virtual Screening for Inhibitors of Lysine-Specific Histone Demethylase 1

A machine learning approach has been applied to virtual screening for lysine specific demethylase 1 (LSD1) inhibitors. LSD1 is an important anti-cancer target. Machine learning models to predict activity were constructed using Morgan molecular fingerprints. The dataset, consisting of 931 molecules with LSD1 inhibition activity, was obtained from the ChEMBL database. An evaluation of several candidate algorithms on the main dataset revealed that the support vector regressor gave the best model, with a coefficient of determination (R2) of 0.703. Virtual screening, using this model, identified five predicted potent inhibitors from the ZINC database comprising more than 300,000 molecules. The virtual screening recovered a known inhibitor, RN1, as well as four compounds where activity against LSD1 had not previously been suggested. Thus, we performed a machine-learning-enabled virtual screening of LSD1 inhibitors using only the structural information of the molecules

High Performance Computing for DNA Sequence Alignment and Assembly

Recent advances in DNA sequencing technology have dramatically increased the scale and scope of DNA sequencing. These data are used for a wide variety of important biological analyzes, including genome sequencing, comparative genomics, transcriptome analysis, and personalized medicine but are complicated by the volume and complexity of the data involved. Given the massive size of these datasets, computational biology must draw on the advances of high performance computing. Two fundamental computations in computational biology are read alignment and genome assembly. Read alignment maps short DNA sequences to a reference genome to discover conserved and polymorphic regions of the genome. Genome assembly computes the sequence of a genome from many short DNA sequences. Both computations benefit from recent advances in high performance computing to efficiently process the huge datasets involved, including using highly parallel graphics processing units (GPUs) as high performance desktop processors, and using the MapReduce framework coupled with cloud computing to parallelize computation to large compute grids. This dissertation demonstrates how these technologies can be used to accelerate these computations by orders of magnitude, and have the potential to make otherwise infeasible computations practical

Doctor of Philosophy

dissertationA modern software system is a composition of parts that are themselves highly complex: operating systems, middleware, libraries, servers, and so on. In principle, compositionality of interfaces means that we can understand any given module independently of the internal workings of other parts. In practice, however, abstractions are leaky, and with every generation, modern software systems grow in complexity. Traditional ways of understanding failures, explaining anomalous executions, and analyzing performance are reaching their limits in the face of emergent behavior, unrepeatability, cross-component execution, software aging, and adversarial changes to the system at run time. Deterministic systems analysis has a potential to change the way we analyze and debug software systems. Recorded once, the execution of the system becomes an independent artifact, which can be analyzed offline. The availability of the complete system state, the guaranteed behavior of re-execution, and the absence of limitations on the run-time complexity of analysis collectively enable the deep, iterative, and automatic exploration of the dynamic properties of the system. This work creates a foundation for making deterministic replay a ubiquitous system analysis tool. It defines design and engineering principles for building fast and practical replay machines capable of capturing complete execution of the entire operating system with an overhead of several percents, on a realistic workload, and with minimal installation costs. To enable an intuitive interface of constructing replay analysis tools, this work implements a powerful virtual machine introspection layer that enables an analysis algorithm to be programmed against the state of the recorded system through familiar terms of source-level variable and type names. To support performance analysis, the replay engine provides a faithful performance model of the original execution during replay

Novel computational techniques for mapping and classifying Next-Generation Sequencing data

Since their emergence around 2006, Next-Generation Sequencing technologies have been revolutionizing biological and medical research. Quickly obtaining an extensive amount of short or long reads of DNA sequence from almost any biological sample enables detecting genomic variants, revealing the composition of species in a metagenome, deciphering cancer biology, decoding the evolution of living or extinct species, or understanding human migration patterns and human history in general. The pace at which the throughput of sequencing technologies is increasing surpasses the growth of storage and computer capacities, which creates new computational challenges in NGS data processing. In this thesis, we present novel computational techniques for read mapping and taxonomic classification. With more than a hundred of published mappers, read mapping might be considered fully solved. However, the vast majority of mappers follow the same paradigm and only little attention has been paid to non-standard mapping approaches. Here, we propound the so-called dynamic mapping that we show to significantly improve the resulting alignments compared to traditional mapping approaches. Dynamic mapping is based on exploiting the information from previously computed alignments, helping to improve the mapping of subsequent reads. We provide the first comprehensive overview of this method and demonstrate its qualities using Dynamic Mapping Simulator, a pipeline that compares various dynamic mapping scenarios to static mapping and iterative referencing. An important component of a dynamic mapper is an online consensus caller, i.e., a program collecting alignment statistics and guiding updates of the reference in the online fashion. We provide Ococo, the first online consensus caller that implements a smart statistics for individual genomic positions using compact bit counters. Beyond its application to dynamic mapping, Ococo can be employed as an online SNP caller in various analysis pipelines, enabling SNP calling from a stream without saving the alignments on disk. Metagenomic classification of NGS reads is another major topic studied in the thesis. Having a database with thousands of reference genomes placed on a taxonomic tree, the task is to rapidly assign a huge amount of NGS reads to tree nodes, and possibly estimate the relative abundance of involved species. In this thesis, we propose improved computational techniques for this task. In a series of experiments, we show that spaced seeds consistently improve the classification accuracy. We provide Seed-Kraken, a spaced seed extension of Kraken, the most popular classifier at present. Furthermore, we suggest ProPhyle, a new indexing strategy based on a BWT-index, obtaining a much smaller and more informative index compared to Kraken. We provide a modified version of BWA that improves the BWT-index for a quick k-mer look-up

Mining a Small Medical Data Set by Integrating the Decision Tree and t-test

[[abstract]]Although several researchers have used statistical methods to prove that aspiration followed by the injection of 95% ethanol left in situ (retention) is an effective treatment for ovarian endometriomas, very few discuss the different conditions that could generate different recovery rates for the patients. Therefore, this study adopts the statistical method and decision tree techniques together to analyze the postoperative status of ovarian endometriosis patients under different conditions. Since our collected data set is small, containing only 212 records, we use all of these data as the training data. Therefore, instead of using a resultant tree to generate rules directly, we use the value of each node as a cut point to generate all possible rules from the tree first. Then, using t-test, we verify the rules to discover some useful description rules after all possible rules from the tree have been generated. Experimental results show that our approach can find some new interesting knowledge about recurrent ovarian endometriomas under different conditions.[[journaltype]]國外[[incitationindex]]EI[[booktype]]紙本[[countrycodes]]FI