Academic literature on the topic 'Genomics workflow'

Scientific Workflows (SWFs) are widely used to model applications in e-Science. In this programming model, scientific applications are described as a set of tasks that have dependencies among them. During the last decades, the execution of scientific workflows has been successfully performed in the available computing infrastructures (supercomputers, clusters and grids) using software programs called Workflow Management Systems (WMSs), which orchestrate the workload on top of these computing infrastructures. However, because each computing infrastructure has its own architecture and each scientific applications exploits efficiently one of these infrastructures, it is necessary to organize the way in which they are executed. WMSs need to get the most out of all the available computing and storage resources. Traditionally, scientific workflow applications have been extensively deployed in high-performance computing infrastructures (such as supercomputers and clusters) and grids. But, in the last years, the advent of cloud computing infrastructures has opened the door of using on-demand infrastructures to complement or even replace local infrastructures. However, new issues have arisen, such as the integration of hybrid resources or the compromise between infrastructure reutilization and elasticity, everything on the basis of cost-efficiency. The main contribution of this thesis is an ad-hoc solution for managing workflows exploiting the capabilities of cloud computing orchestrators to deploy resources on demand according to the workload and to combine heterogeneous cloud providers (such as on-premise clouds and public clouds) and traditional infrastructures (supercomputers and clusters) to minimize costs and response time. The thesis does not propose yet another WMS, but demonstrates the benefits of the integration of cloud orchestration when running complex workflows. The thesis shows several configuration experiments and multiple heterogeneous backends from a realistic comparative genomics workflow called Orthosearch, to migrate memory-intensive workload to public infrastructures while keeping other blocks of the experiment running locally. The running time and cost of the experiments is computed and best practices are suggested.<br>Los flujos de trabajo científicos son comúnmente usados para modelar aplicaciones en e-Ciencia. En este modelo de programación, las aplicaciones científicas se describen como un conjunto de tareas que tienen dependencias entre ellas. Durante las últimas décadas, la ejecución de flujos de trabajo científicos se ha llevado a cabo con éxito en las infraestructuras de computación disponibles (supercomputadores, clústers y grids) haciendo uso de programas software llamados Gestores de Flujos de Trabajos, los cuales distribuyen la carga de trabajo en estas infraestructuras de computación. Sin embargo, debido a que cada infraestructura de computación posee su propia arquitectura y cada aplicación científica explota eficientemente una de estas infraestructuras, es necesario organizar la manera en que se ejecutan. Los Gestores de Flujos de Trabajo necesitan aprovechar el máximo todos los recursos de computación y almacenamiento disponibles. Habitualmente, las aplicaciones científicas de flujos de trabajos han sido ejecutadas en recursos de computación de altas prestaciones (tales como supercomputadores y clústers) y grids. Sin embargo, en los últimos años, la aparición de las infraestructuras de computación en la nube ha posibilitado el uso de infraestructuras bajo demanda para complementar o incluso reemplazar infraestructuras locales. No obstante, este hecho plantea nuevas cuestiones, tales como la integración de recursos híbridos o el compromiso entre la reutilización de la infraestructura y la elasticidad, todo ello teniendo en cuenta que sea eficiente en el coste. La principal contribución de esta tesis es una solución ad-hoc para gestionar flujos de trabajos explotando las capacidades de los orquestadores de recursos de computación en la nube para desplegar recursos bajo demando según la carga de trabajo y combinar proveedores de computación en la nube heterogéneos (privados y públicos) e infraestructuras tradicionales (supercomputadores y clústers) para minimizar el coste y el tiempo de respuesta. La tesis no propone otro gestor de flujos de trabajo más, sino que demuestra los beneficios de la integración de la orquestación de la computación en la nube cuando se ejecutan flujos de trabajo complejos. La tesis muestra experimentos con diferentes configuraciones y múltiples plataformas heterogéneas, haciendo uso de un flujo de trabajo real de genómica comparativa llamado Orthosearch, para traspasar cargas de trabajo intensivas de memoria a infraestructuras públicas mientras se mantienen otros bloques del experimento ejecutándose localmente. El tiempo de respuesta y el coste de los experimentos son calculados, además de sugerir buenas prácticas.<br>Els fluxos de treball científics són comunament usats per a modelar aplicacions en e-Ciència. En aquest model de programació, les aplicacions científiques es descriuen com un conjunt de tasques que tenen dependències entre elles. Durant les últimes dècades, l'execució de fluxos de treball científics s'ha dut a terme amb èxit en les infraestructures de computació disponibles (supercomputadors, clústers i grids) fent ús de programari anomenat Gestors de Fluxos de Treballs, els quals distribueixen la càrrega de treball en aquestes infraestructures de computació. No obstant açò, a causa que cada infraestructura de computació posseeix la seua pròpia arquitectura i cada aplicació científica explota eficientment una d'aquestes infraestructures, és necessari organitzar la manera en què s'executen. Els Gestors de Fluxos de Treball necessiten aprofitar el màxim tots els recursos de computació i emmagatzematge disponibles. Habitualment, les aplicacions científiques de fluxos de treballs han sigut executades en recursos de computació d'altes prestacions (tals com supercomputadors i clústers) i grids. No obstant açò, en els últims anys, l'aparició de les infraestructures de computació en el núvol ha possibilitat l'ús d'infraestructures sota demanda per a complementar o fins i tot reemplaçar infraestructures locals. No obstant açò, aquest fet planteja noves qüestions, tals com la integració de recursos híbrids o el compromís entre la reutilització de la infraestructura i l'elasticitat, tot açò tenint en compte que siga eficient en el cost. La principal contribució d'aquesta tesi és una solució ad-hoc per a gestionar fluxos de treballs explotant les capacitats dels orquestadors de recursos de computació en el núvol per a desplegar recursos baix demande segons la càrrega de treball i combinar proveïdors de computació en el núvol heterogenis (privats i públics) i infraestructures tradicionals (supercomputadors i clústers) per a minimitzar el cost i el temps de resposta. La tesi no proposa un gestor de fluxos de treball més, sinó que demostra els beneficis de la integració de l'orquestració de la computació en el núvol quan s'executen fluxos de treball complexos. La tesi mostra experiments amb diferents configuracions i múltiples plataformes heterogènies, fent ús d'un flux de treball real de genòmica comparativa anomenat Orthosearch, per a traspassar càrregues de treball intensives de memòria a infraestructures públiques mentre es mantenen altres blocs de l'experiment executant-se localment. El temps de resposta i el cost dels experiments són calculats, a més de suggerir bones pràctiques.<br>Carrión Collado, AA. (2017). Management of generic and multi-platform workflows for exploiting heterogeneous environments on e-Science [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/86179<br>TESIS

Background: With the advances in next-generation sequencing (NGS) technology and significant reductions in sequencing costs, it is now possible to sequence large collections of germplasm in crops for detecting genome-scale genetic variations and to apply the knowledge towards improvements in traits. To efficiently facilitate large-scale NGS resequencing data analysis of genomic variations, we have developed " PGen", an integrated and optimized workflow using the Extreme Science and Engineering Discovery Environment (XSEDE) high-performance computing (HPC) virtual system, iPlant cloud data storage resources and Pegasus workflow management system (Pegasus-WMS). The workflow allows users to identify single nucleotide polymorphisms (SNPs) and insertion-deletions (indels), perform SNP annotations and conduct copy number variation analyses on multiple resequencing datasets in a user-friendly and seamless way. Results: We have developed both a Linux version in GitHub (https:// github. com/ pegasus-isi/ PGen-GenomicVariationsWorkflow) and a web-based implementation of the PGen workflow integrated within the Soybean Knowledge Base (SoyKB), (http:// soykb. org/ Pegasus/ index. php). Using PGen, we identified 10,218,140 single-nucleotide polymorphisms (SNPs) and 1,398,982 indels from analysis of 106 soybean lines sequenced at 15X coverage. 297,245 non-synonymous SNPs and 3330 copy number variation (CNV) regions were identified from this analysis. SNPs identified using PGen from additional soybean resequencing projects adding to 500+ soybean germplasm lines in total have been integrated. These SNPs are being utilized for trait improvement using genotype to phenotype prediction approaches developed in-house. In order to browse and access NGS data easily, we have also developed an NGS resequencing data browser (http:// soykb. org/ NGS_ Resequence/ NGS_ index. php) within SoyKB to provide easy access to SNP and downstream analysis results for soybean researchers. Conclusion: PGen workflow has been optimized for the most efficient analysis of soybean data using thorough testing and validation. This research serves as an example of best practices for development of genomics data analysis workflows by integrating remote HPC resources and efficient data management with ease of use for biological users. PGen workflow can also be easily customized for analysis of data in other species.

The vast majority of the human genome (~98%) is non-coding. A symphony of non-coding sequences resides in the genome, interacting with genes and the environment to tune gene expression. Functional non-coding sequences include enhancers, silencers, promoters, non-coding RNA and insulators. Variation in these non-coding sequences can cause disease, yet clinical sequencing in patients with rare Mendelian disease currently focuses mostly on variants in the ~2% of the genome that codes for protein. Indeed, variants in protein-coding genes that can explain a phenotype are identified in less than half of patients with suspected genetic disease by whole exome sequencing (WES). With the dramatic reduction in the cost of whole genome sequencing (WGS), development of algorithms to detect variants longer than 50 bp (structural variants, SVs), and improved annotation of the non-coding genome, it is now possible to interrogate the entire spectrum of genetic variation to identify a pathogenic mutation. A comprehensive pipeline is needed to analyze non-coding variation and structural variation from WGS. In this thesis, I developed and benchmarked a bioinformatics workflow to detect pathogenic non-coding SNVs/indels and pathogenic SVs, and applied this workflow to unsolved patients with rare Mendelian disorders. The pipeline detected ~80-90% of deletions, ~90% of duplications, ~65% inversions, and ~50% of insertions in a simulated genome and the NA12878 genome. The pipeline captured the majority of known pathogenic non-coding single nucleotide variant (SNVs) and insertion deletions (indels), and selectively prioritized a spiked-in known pathogenic non-coding SNV. Several interesting candidate variants were detected in patients, but none could be convincingly implicated as pathogenic. The bioinformatic workflow described in this thesis is complementary to sequencing pipelines that analyze only protein-coding variants from whole genomes. Application of this workflow to larger cohorts of patients with rare Mendelian diseases should identify pathogenic non-coding variants and SVs to increase diagnostic yield of clinical sequencing studies, assist management of genetic diseases, and contribute knowledge of novel pathogenic variants to the scientific community.<br>Science, Faculty of<br>Graduate

Technological advancements in mass spectrometry allowing quantification of almost complete proteomes make proteomics a key platform for generating unique functional molecular data. Furthermore, the integrative analysis of genomic and proteomic data, termed proteogenomics, has emerged as a new field revealing insights into gene expression regulation, cell signalling, and disease processes. However, the lack of software tools for high-throughput integration and unbiased modification and variant detection hinder efforts for large-scale proteogenomics studies. The main objectives of this work are to address these issues by developing and applying new software tools and data analysis methods. Firstly, I address mapping of peptide sequences to reference genomes. I introduce a novel tool for high-throughput mapping and highlight its unique features facilitating quantitative and post-translational modification mapping alongside accounting for amino acid substitutions. The performance is benchmarked. Furthermore, I offer an additional tool that permits generation of web accessible hubs of genome wide mappings. To enable unbiased identification of post-translational modifications and amino acid substitutions for high resolution mass spectrometry data, I present algorithmic updates the mass tolerant blind spectrum comparison tool ’MS SMiV’. I demonstrate the applicability of the changes by benchmarking against a published mass tolerant database search of a high resolution tandem mass spectrometry dataset. I then present the application of ‘MS SMiV’ on a panel of 50 colorectal cancer cell lines. I show that the adaption of ‘MS SMiV’ outperforms traditional sequence database based identification of single amino acid variants. Furthermore, I highlight the utility of mass tolerant spectrum matching in combination with isobaric labelled quantitative proteomics in distinguishing between post-translational modifications and amino acid variants of similar mass. In the last part of this work I integrate both tools with a high-throughput proteogenomic identification pipeline and apply it to a pilot study of chondrocytes derived from 12 osteoarthritic individuals. I show the value of this approach in identifying variation between individuals and molecular levels and highlight them with individual examples. I show that multi-plexed proteogenomics can be used to infer genotypes of individuals.

Devido à grande diversidade de microrganismos desconhecidos no meio ambiente, 99% deles não podem ser cultivados nos meios de cultura tradicionais dos laboratórios. Para isso, projetos metagenômicos são propostos para estudar comunidades microbianas presentes no meio ambiente, a partir de técnicas moleculares, em especial o seqüenciamento. Dessa forma, para os próximos anos é esperado um acúmulo de seqüências produzidas por esses projetos. As seqüências produzidas pelos projetos genomas e metagenomas apresentam vários desafios para o tratamento, armazenamento e análise, como exemplo: a busca de clones contendo genes de interesse. Este trabalho apresenta uma abordagem algébrica que define e gerencia de forma dinâmica as regras para a seleção de clones em bibliotecas genômicas e metagenômicas, que se baseiam em álgebra de processos. Além disso, uma interface web foi desenvolvida para permitir que os pesquisadores criem e executem facilmente suas próprias regras de seleção de clones em bancos de dados de seqüências genômicas e metagenômicas. Este software foi testado em bibliotecas genômicas e metagenômicas e foi capaz de selecionar clones contendo genes de interesse.<br>Due to the wide diversity of unknown organisms in the environment, 99% of them cannot be grown in traditional culture medium in laboratories. Therefore, metagenomics projects are proposed to study microbial communities present in the environment, from molecular techniques, especially the sequencing. Thereby, for the coming years it is expected an accumulation of sequences produced by these projects. Thus, the sequences produced by genomics and metagenomics projects present several challenges for the treatment, storing and analysis such as: the search for clones containing genes of interest. This work presents an algebraic approach that defines it dynamically and manages the rules of the selection of clones in genomic and metagenomic libraries, which are based on process algebra. Furthermore, a web interface was developed to allow researchers to easily create and execute their own rules to select clones in genomic and metagenomic sequence database. This software was tested in genomics and metagenomics libraries and it was able to select clones containing genes of interest.

>Magister Scientiae - MSc<br>Functional genomics determines the biological functions of genes on a global scale by using large volumes of data obtained through techniques including next-generation sequencing (NGS). The application of NGS in biomedical research is gaining in momentum, and with its adoption becoming more widespread, there is an increasing need for access to customizable computational workflows that can simplify, and offer access to, computer intensive analyses of genomic data. In this study, the Galaxy and Ruffus frameworks were designed and implemented with a view to address the challenges faced in biomedical research. Galaxy, a graphical web-based framework, allows researchers to build a graphical NGS data analysis pipeline for accessible, reproducible, and collaborative data-sharing. Ruffus, a UNIX command-line framework used by bioinformaticians as Python library to write scripts in object-oriented style, allows for building a workflow in terms of task dependencies and execution logic. In this study, a dual data analysis technique was explored which focuses on a comparative evaluation of Galaxy and Ruffus frameworks that are used in composing analysis pipelines. To this end, we developed an analysis pipeline in Galaxy, and Ruffus, for the analysis of Mycobacterium tuberculosis sequence data. Furthermore, this study aimed to compare the Galaxy framework to Ruffus with preliminary analysis revealing that the analysis pipeline in Galaxy displayed a higher percentage of load and store instructions. In comparison, pipelines in Ruffus tended to be CPU bound and memory intensive. The CPU usage, memory utilization, and runtime execution are graphically represented in this study. Our evaluation suggests that workflow frameworks have distinctly different features from ease of use, flexibility, and portability, to architectural designs.

L'objectif de mon travail de thèse était de développer des outils bio informatiques permettant d'améliorer la traditionnelle gestion de l'information scientifique au sein d'un grand centre de recherche et en particulier au sein d'une plateforme de génomique. Trois outils ont été développés: un cahier de laboratoire électronique, un système de gestion de l'information de laboratoire pour des applications de génomique dont le séquençage de nouvelle génération, ainsi qu'un système de gestion des échantillons pour de grandes bio-banques. Ce travail a été réalisé en étroite collaboration avec des biologistes, épidémiologistes et informaticiens. Il a également inclus la mise en place d'interactions entre les différents outils pour former un système informatique intégré. Les trois outils ont été rapidement adoptés par l'ensemble des scientifiques du centre de recherche et sont désormais utilisés au quotidien pour le suivi de toutes les activités de laboratoire mais aussi plus globalement pour les autres activités scientifiques du centre de recherche. Ces outils sont transposables dans d'autres instituts de recherche<br>The aim of my thesis work was to develop bioinformatics tools to improve the traditional scientific information management within a large research centre and especially within a genomics platform. Three tools have been developed: an electronic laboratory notebook, a laboratory information management system for genomics applications including next generation sequencing, as well as a sample management system for large biobanks. This work has been conducted in close collaboration with biologists, epidemiologists and IT specialists. It has also included the setup of interactions between the different tools to make an integrated IT system. The three tools have been rapidly adopted by all the scientists of the research centre and are now daily used for the tracking of all the laboratory’s activities but also more globally for the research centre’s other scientific activities. These tools are transposable in other research institutes

Indiana University-Purdue University Indianapolis (IUPUI)<br>A Laboratory Information Management Systems (LIMS) is designed to manage laboratory processes and data. It has the ability to extend the core functionality of the LIMS through configuration tools and add-on modules to support the implementation of complex laboratory workflows. The purpose of this project is to demonstrate how laboratory data and processes from a complex workflow can be implemented using a LIMS. Genomic samples have become an important part of the drug development process due to advances in molecular testing technology. This technology evaluates genomic material for disease markers and provides efficient, cost-effective, and accurate results for a growing number of clinical indications. The preparation of the genomic samples for evaluation requires a complex laboratory process called the precision aliquotting workflow. The precision aliquotting workflow processes genomic samples into precisely created aliquots for analysis. The workflow is defined by a set of aliquotting scheme attributes that are executed based on scheme specific rules logic. The aliquotting scheme defines the attributes of each aliquot based on the achieved sample recovery of the genomic sample. The scheme rules logic executes the creation of the aliquots based on the scheme definitions. LabWare LIMS is a Windows® based open architecture system that manages laboratory data and workflow processes. A LabWare LIMS model was developed to implement the precision aliquotting workflow using a combination of core functionality and configured code.