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    Date Issued2020 (1)2018 (2)Author
    Ozturk, Ahmet R. (3)
    Chen, Hao (2)Mello, Craig C. (2)Shen, En-Zhi (2)Shirayama, Masaki (2)View MoreUMass Chan AffiliationProgram in Bioinformatics and Integrative Biology (3)RNA Therapeutics Institute (3)Bioinformatics Core (1)Garber Lab (1)Program in Molecular Medicine (1)Document TypeJournal Article (3)KeywordBiochemistry, Biophysics, and Structural Biology (2)Bioinformatics (2)Computational Biology (2)Amino Acids, Peptides, and Proteins (1)Argonaute (1)View MoreJournalBMC genomics (1)Cell (1)Molecular cell (1)

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    DolphinNext: a distributed data processing platform for high throughput genomics

    Yukselen, Onur; Turkyilmaz, Osman; Ozturk, Ahmet R.; Garber, Manuel; Kucukural, Alper (2020-04-19)
    BACKGROUND: The emergence of high throughput technologies that produce vast amounts of genomic data, such as next-generation sequencing (NGS) is transforming biological research. The dramatic increase in the volume of data, the variety and continuous change of data processing tools, algorithms and databases make analysis the main bottleneck for scientific discovery. The processing of high throughput datasets typically involves many different computational programs, each of which performs a specific step in a pipeline. Given the wide range of applications and organizational infrastructures, there is a great need for highly parallel, flexible, portable, and reproducible data processing frameworks. Several platforms currently exist for the design and execution of complex pipelines. Unfortunately, current platforms lack the necessary combination of parallelism, portability, flexibility and/or reproducibility that are required by the current research environment. To address these shortcomings, workflow frameworks that provide a platform to develop and share portable pipelines have recently arisen. We complement these new platforms by providing a graphical user interface to create, maintain, and execute complex pipelines. Such a platform will simplify robust and reproducible workflow creation for non-technical users as well as provide a robust platform to maintain pipelines for large organizations. RESULTS: To simplify development, maintenance, and execution of complex pipelines we created DolphinNext. DolphinNext facilitates building and deployment of complex pipelines using a modular approach implemented in a graphical interface that relies on the powerful Nextflow workflow framework by providing 1. A drag and drop user interface that visualizes pipelines and allows users to create pipelines without familiarity in underlying programming languages. 2. Modules to execute and monitor pipelines in distributed computing environments such as high-performance clusters and/or cloud 3. Reproducible pipelines with version tracking and stand-alone versions that can be run independently. 4. Modular process design with process revisioning support to increase reusability and pipeline development efficiency. 5. Pipeline sharing with GitHub and automated testing 6. Extensive reports with R-markdown and shiny support for interactive data visualization and analysis. CONCLUSION: DolphinNext is a flexible, intuitive, web-based data processing and analysis platform that enables creating, deploying, sharing, and executing complex Nextflow pipelines with extensive revisioning and interactive reporting to enhance reproducible results.
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    ZNFX-1 Functions within Perinuclear Nuage to Balance Epigenetic Signals

    Ishidate, Takao; Ozturk, Ahmet R.; Durning, Daniel J.; Sharma, Rita; Shen, En-Zhi; Chen, Hao; Seth, Meetu; Shirayama, Masaki; Mello, Craig C. (2018-05-17)
    Animal cells have a remarkable capacity to adopt durable and heritable gene expression programs or epigenetic states that define the physical properties and diversity of somatic cell types. The maintenance of epigenetic programs depends on poorly understood pathways that prevent gain or loss of inherited signals. In the germline, epigenetic factors are enriched in liquid-like perinuclear condensates called nuage. Here, we identify the deeply conserved helicase-domain protein, ZNFX-1, as an epigenetic regulator and component of nuage that interacts with Argonaute systems to balance epigenetic inheritance. Our findings suggest that ZNFX-1 promotes the 3' recruitment of machinery that propagates the small RNA epigenetic signal and thus counteracts a tendency for Argonaute targeting to shift 5' along the mRNA. These functional insights support the idea that recently identified subdomains of nuage, including ZNFX-1 granules or "Z-granules," may define spatial and temporal zones of molecular activity during epigenetic regulation.
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    Identification of piRNA Binding Sites Reveals the Argonaute Regulatory Landscape of the C. elegans Germline

    Shen, En-Zhi; Chen, Hao; Ozturk, Ahmet R.; Tu, Shikui; Shirayama, Masaki; Tang, Wen; Ding, Yue-He; Dai, Si-Yuan; Weng, Zhiping; Mello, Craig C. (2018-02-22)
    piRNAs (Piwi-interacting small RNAs) engage Piwi Argonautes to silence transposons and promote fertility in animal germlines. Genetic and computational studies have suggested that C. elegans piRNAs tolerate mismatched pairing and in principle could target every transcript. Here we employ in vivo cross-linking to identify transcriptome-wide interactions between piRNAs and target RNAs. We show that piRNAs engage all germline mRNAs and that piRNA binding follows microRNA-like pairing rules. Targeting correlates better with binding energy than with piRNA abundance, suggesting that piRNA concentration does not limit targeting. In mRNAs silenced by piRNAs, secondary small RNAs accumulate at the center and ends of piRNA binding sites. In germline-expressed mRNAs, however, targeting by the CSR-1 Argonaute correlates with reduced piRNA binding density and suppression of piRNA-associated secondary small RNAs. Our findings reveal physiologically important and nuanced regulation of individual piRNA targets and provide evidence for a comprehensive post-transcriptional regulatory step in germline gene expression.
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