The LONI QC System: A Semi-Automated, Web-Based and Freely-Available Environment for the Comprehensive Quality Control of Neuroimaging Data.

Quantifying, controlling, and monitoring image quality is an essential prerequisite for ensuring the validity and reproducibility of many types of neuroimaging data analyses. Implementation of quality control (QC) procedures is the key to ensuring that neuroimaging data are of high-quality and their validity in the subsequent analyses. We introduce the QC system of the Laboratory of Neuro Imaging (LONI): a web-based system featuring a workflow for the assessment of various modality and contrast brain imaging data. The design allows users to anonymously upload imaging data to the LONI-QC system. It then computes an exhaustive set of QC metrics which aids users to perform a standardized QC by generating a range of scalar and vector statistics. These procedures are performed in parallel using a large compute cluster. Finally, the system offers an automated QC procedure for structural MRI, which can flag each QC metric as being 'good' or 'bad.' Validation using various sets of data acquired from a single scanner and from multiple sites demonstrated the reproducibility of our QC metrics, and the sensitivity and specificity of the proposed Auto QC to 'bad' quality images in comparison to visual inspection. To the best of our knowledge, LONI-QC is the first online QC system that uniquely supports the variety of functionality where we compute numerous QC metrics and perform visual/automated image QC of multi-contrast and multi-modal brain imaging data. The LONI-QC system has been used to assess the quality of large neuroimaging datasets acquired as part of various multi-site studies such as the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Study and the Alzheimer's Disease Neuroimaging Initiative (ADNI). LONI-QC's functionality is freely available to users worldwide and its adoption by imaging researchers is likely to contribute substantially to upholding high standards of brain image data quality and to implementing these standards across the neuroimaging community.

Interacting with the National Database for Autism Research (NDAR) via the LONI Pipeline workflow environment.

Under the umbrella of the National Database for Clinical Trials (NDCT) related to mental illnesses, the National Database for Autism Research (NDAR) seeks to gather, curate, and make openly available neuroimaging data from NIH-funded studies of autism spectrum disorder (ASD). NDAR has recently made its database accessible through the LONI Pipeline workflow design and execution environment to enable large-scale analyses of cortical architecture and function via local, cluster, or "cloud"-based computing resources. This presents a unique opportunity to overcome many of the customary limitations to fostering biomedical neuroimaging as a science of discovery. Providing open access to primary neuroimaging data, workflow methods, and high-performance computing will increase uniformity in data collection protocols, encourage greater reliability of published data, results replication, and broaden the range of researchers now able to perform larger studies than ever before. To illustrate the use of NDAR and LONI Pipeline for performing several commonly performed neuroimaging processing steps and analyses, this paper presents example workflows useful for ASD neuroimaging researchers seeking to begin using this valuable combination of online data and computational resources. We discuss the utility of such database and workflow processing interactivity as a motivation for the sharing of additional primary data in ASD research and elsewhere.

High-throughput neuroimaging-genetics computational infrastructure.

Many contemporary neuroscientific investigations face significant challenges in terms of data management, computational processing, data mining, and results interpretation. These four pillars define the core infrastructure necessary to plan, organize, orchestrate, validate, and disseminate novel scientific methods, computational resources, and translational healthcare findings. Data management includes protocols for data acquisition, archival, query, transfer, retrieval, and aggregation. Computational processing involves the necessary software, hardware, and networking infrastructure required to handle large amounts of heterogeneous neuroimaging, genetics, clinical, and phenotypic data and meta-data. Data mining refers to the process of automatically extracting data features, characteristics and associations, which are not readily visible by human exploration of the raw dataset. Result interpretation includes scientific visualization, community validation of findings and reproducible findings. In this manuscript we describe the novel high-throughput neuroimaging-genetics computational infrastructure available at the Institute for Neuroimaging and Informatics (INI) and the Laboratory of Neuro Imaging (LONI) at University of Southern California (USC). INI and LONI include ultra-high-field and standard-field MRI brain scanners along with an imaging-genetics database for storing the complete provenance of the raw and derived data and meta-data. In addition, the institute provides a large number of software tools for image and shape analysis, mathematical modeling, genomic sequence processing, and scientific visualization. A unique feature of this architecture is the Pipeline environment, which integrates the data management, processing, transfer, and visualization. Through its client-server architecture, the Pipeline environment provides a graphical user interface for designing, executing, monitoring validating, and disseminating of complex protocols that utilize diverse suites of software tools and web-services. These pipeline workflows are represented as portable XML objects which transfer the execution instructions and user specifications from the client user machine to remote pipeline servers for distributed computing. Using Alzheimer's and Parkinson's data, we provide several examples of translational applications using this infrastructure.

The perfect neuroimaging-genetics-computation storm: collision of petabytes of data, millions of hardware devices and thousands of software tools.

The volume, diversity and velocity of biomedical data are exponentially increasing providing petabytes of new neuroimaging and genetics data every year. At the same time, tens-of-thousands of computational algorithms are developed and reported in the literature along with thousands of software tools and services. Users demand intuitive, quick and platform-agnostic access to data, software tools, and infrastructure from millions of hardware devices. This explosion of information, scientific techniques, computational models, and technological advances leads to enormous challenges in data analysis, evidence-based biomedical inference and reproducibility of findings. The Pipeline workflow environment provides a crowd-based distributed solution for consistent management of these heterogeneous resources. The Pipeline allows multiple (local) clients and (remote) servers to connect, exchange protocols, control the execution, monitor the states of different tools or hardware, and share complete protocols as portable XML workflows. In this paper, we demonstrate several advanced computational neuroimaging and genetics case-studies, and end-to-end pipeline solutions. These are implemented as graphical workflow protocols in the context of analyzing imaging (sMRI, fMRI, DTI), phenotypic (demographic, clinical), and genetic (SNP) data.

Next generation sequence analysis and computational genomics using graphical pipeline workflows.

Whole-genome and exome sequencing have already proven to be essential and powerful methods to identify genes responsible for simple Mendelian inherited disorders. These methods can be applied to complex disorders as well, and have been adopted as one of the current mainstream approaches in population genetics. These achievements have been made possible by next generation sequencing (NGS) technologies, which require substantial bioinformatics resources to analyze the dense and complex sequence data. The huge analytical burden of data from genome sequencing might be seen as a bottleneck slowing the publication of NGS papers at this time, especially in psychiatric genetics. We review the existing methods for processing NGS data, to place into context the rationale for the design of a computational resource. We describe our method, the Graphical Pipeline for Computational Genomics (GPCG), to perform the computational steps required to analyze NGS data. The GPCG implements flexible workflows for basic sequence alignment, sequence data quality control, single nucleotide polymorphism analysis, copy number variant identification, annotation, and visualization of results. These workflows cover all the analytical steps required for NGS data, from processing the raw reads to variant calling and annotation. The current version of the pipeline is freely available at http://pipeline.loni.ucla.edu. These applications of NGS analysis may gain clinical utility in the near future (e.g., identifying miRNA signatures in diseases) when the bioinformatics approach is made feasible. Taken together, the annotation tools and strategies that have been developed to retrieve information and test hypotheses about the functional role of variants present in the human genome will help to pinpoint the genetic risk factors for psychiatric disorders.

Applications of the pipeline environment for visual informatics and genomics computations.

BACKGROUND: Contemporary informatics and genomics research require efficient, flexible and robust management of large heterogeneous data, advanced computational tools, powerful visualization, reliable hardware infrastructure, interoperability of computational resources, and detailed data and analysis-protocol provenance. The Pipeline is a client-server distributed computational environment that facilitates the visual graphical construction, execution, monitoring, validation and dissemination of advanced data analysis protocols. RESULTS: This paper reports on the applications of the LONI Pipeline environment to address two informatics challenges - graphical management of diverse genomics tools, and the interoperability of informatics software. Specifically, this manuscript presents the concrete details of deploying general informatics suites and individual software tools to new hardware infrastructures, the design, validation and execution of new visual analysis protocols via the Pipeline graphical interface, and integration of diverse informatics tools via the Pipeline eXtensible Markup Language syntax. We demonstrate each of these processes using several established informatics packages (e.g., miBLAST, EMBOSS, mrFAST, GWASS, MAQ, SAMtools, Bowtie) for basic local sequence alignment and search, molecular biology data analysis, and genome-wide association studies. These examples demonstrate the power of the Pipeline graphical workflow environment to enable integration of bioinformatics resources which provide a well-defined syntax for dynamic specification of the input/output parameters and the run-time execution controls. CONCLUSIONS: The LONI Pipeline environment http://pipeline.loni.ucla.edu provides a flexible graphical infrastructure for efficient biomedical computing and distributed informatics research. The interactive Pipeline resource manager enables the utilization and interoperability of diverse types of informatics resources. The Pipeline client-server model provides computational power to a broad spectrum of informatics investigators--experienced developers and novice users, user with or without access to advanced computational-resources (e.g., Grid, data), as well as basic and translational scientists. The open development, validation and dissemination of computational networks (pipeline workflows) facilitates the sharing of knowledge, tools, protocols and best practices, and enables the unbiased validation and replication of scientific findings by the entire community.

Neuroimaging study designs, computational analyses and data provenance using the LONI pipeline.

Modern computational neuroscience employs diverse software tools and multidisciplinary expertise to analyze heterogeneous brain data. The classical problems of gathering meaningful data, fitting specific models, and discovering appropriate analysis and visualization tools give way to a new class of computational challenges--management of large and incongruous data, integration and interoperability of computational resources, and data provenance. We designed, implemented and validated a new paradigm for addressing these challenges in the neuroimaging field. Our solution is based on the LONI Pipeline environment [3], [4], a graphical workflow environment for constructing and executing complex data processing protocols. We developed study-design, database and visual language programming functionalities within the LONI Pipeline that enable the construction of complete, elaborate and robust graphical workflows for analyzing neuroimaging and other data. These workflows facilitate open sharing and communication of data and metadata, concrete processing protocols, result validation, and study replication among different investigators and research groups. The LONI Pipeline features include distributed grid-enabled infrastructure, virtualized execution environment, efficient integration, data provenance, validation and distribution of new computational tools, automated data format conversion, and an intuitive graphical user interface. We demonstrate the new LONI Pipeline features using large scale neuroimaging studies based on data from the International Consortium for Brain Mapping [5] and the Alzheimer's Disease Neuroimaging Initiative [6]. User guides, forums, instructions and downloads of the LONI Pipeline environment are available at http://pipeline.loni.ucla.edu.

Efficient, Distributed and Interactive Neuroimaging Data Analysis Using the LONI Pipeline.

The LONI Pipeline is a graphical environment for construction, validation and execution of advanced neuroimaging data analysis protocols (Rex et al., 2003). It enables automated data format conversion, allows Grid utilization, facilitates data provenance, and provides a significant library of computational tools. There are two main advantages of the LONI Pipeline over other graphical analysis workflow architectures. It is built as a distributed Grid computing environment and permits efficient tool integration, protocol validation and broad resource distribution. To integrate existing data and computational tools within the LONI Pipeline environment, no modification of the resources themselves is required. The LONI Pipeline provides several types of process submissions based on the underlying server hardware infrastructure. Only workflow instructions and references to data, executable scripts and binary instructions are stored within the LONI Pipeline environment. This makes it portable, computationally efficient, distributed and independent of the individual binary processes involved in pipeline data-analysis workflows. We have expanded the LONI Pipeline (V.4.2) to include server-to-server (peer-to-peer) communication and a 3-tier failover infrastructure (Grid hardware, Sun Grid Engine/Distributed Resource Management Application API middleware, and the Pipeline server). Additionally, the LONI Pipeline provides three layers of background-server executions for all users/sites/systems. These new LONI Pipeline features facilitate resource-interoperability, decentralized computing, construction and validation of efficient and robust neuroimaging data-analysis workflows. Using brain imaging data from the Alzheimer's Disease Neuroimaging Initiative (Mueller et al., 2005), we demonstrate integration of disparate resources, graphical construction of complex neuroimaging analysis protocols and distributed parallel computing. The LONI Pipeline, its features, specifications, documentation and usage are available online (http://Pipeline.loni.ucla.edu).