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Raveendran, K.

Publications and source records attributed to Raveendran, K..

4 recordsLinked to original sources

Track Hub Quickload Translator: Convert Track Hub or Quickload data for viewing in the UCSC Genome Browser or the Integrated Genome Browser

Summary: Genome browsers are essential for understanding genomic data in detail but use incompatible data repository formats and access protocols, limiting their use. We present a new web application Hub Facade that translates the Track Hub format used by the UCSC Genome Browser into the Quickload format used by the Integrated Genome Browser (IGB), and vice versa. We used the Facade's translation capability to write a single-page web application for IGB users to search and add UCSC-curated Hubs to IGB for exploration and visual analysis. We created a new IGB App (GenArk Genomes) that uses the Facade to automate importing genome assemblies from GenArk, a Hub-based repository with nearly 50,000 genomes hosted by the UCSC Genome Browser team. An example use case investigating alternative splicing of human gene MEOX1 shows how using both browsers to view the same data via the Hub Facade promotes understanding and discovery. Availability and Implementation: Hub Facade is free, open-source software deployed at translate.bioviz.org. Code is available from git repositories at [bitbucket.org|github.com]/lorainelab/hub-facade. The use case is available as Supplemental File 1.

bioinformatics↗

Chromosome axis protein SYCP2 recruits HORMAD2 to enable meiotic synapsis quality control in mice

Faithful chromosome segregation during meiosis depends on accurate recombination and synapsis of homologous chromosomes. These processes are monitored in mammals by checkpoint mechanisms involving the meiotic HORMA-domain proteins HORMAD1 and HORMAD2, which bind unsynapsed chromosome axes and promote activation of the DNA damage-response kinase ATR independently of DNA double-strand breaks (DSBs). However, no mechanism for axis recruitment of HORMAD1 or HORMAD2 had been demonstrated, nor had its role in checkpoint function been tested. We establish that a putative HORMAD-interacting region--the closure motif (CM)--within the chromosome-axis component SYCP2 is selectively required for HORMAD2, but not HORMAD1, localization. Deletion of the SYCP2 CM disrupts SYCP2-HORMAD2 complexes and prevents HORMAD2 axis binding without affecting axis assembly or recombination. Consequently, ATR accumulation and signaling on unsynapsed axes are reduced, and the prophase checkpoint malfunctions in a sexually dimorphic manner--causing aberrant elimination of synapsis-proficient spermatocytes and persistence of asynaptic oocytes. The phenotypes of SYCP2-CM-deficient and HORMAD2-null mice are indistinguishable, establishing the requirement for HORMAD2 axis recruitment in synapsis surveillance. We propose that axial recruitment generates a HORMAD2 scaffold that drives clustering-mediated ATR network activation independently of DSBs, thereby linking chromosome-axis architecture to synapsis quality control in mammalian meiosis.

cell biology↗

Seeding the meiotic DNA break machinery and initiating recombination on chromosome axes

Programmed DNA double-strand break (DSB) formation is a unique meiotic feature that initiates recombination-mediated linking of homologous chromosomes, thereby enabling chromosome number halving in meiosis. DSBs are generated on chromosome axes by heterooligomeric focal clusters of DSB-factors. Whereas DNA-driven protein condensation is thought to assemble the DSB-machinery, its targeting to chromosome axes is poorly understood. We discovered in mice that efficient biogenesis of DSB-machinery clusters requires seeding by axial IHO1 platforms, which are based on a DBF4-dependent kinase (DDK)-modulated interaction between IHO1 and the chromosomal axis component HORMAD1. IHO1-HORMAD1-mediated seeding of the DSB-machinery on axes ensures sufficiency of DSBs for efficient pairing of homologous chromosomes. Without IHO1-HORMAD1 interaction, residual DSBs depend on ANKRD31, which enhances both the seeding and the growth of DSB-machinery clusters. Thus, recombination initiation is ensured by complementary pathways that differentially support seeding and growth of DSB-machinery clusters, thereby synergistically enabling DSB-machinery condensation on chromosomal axes.

cell biology↗

BioViz Connect: Web application linking CyVerse cloud resources to genomic visualization in the Integrated Genome Browser

Genomics researchers do better work when they can interactively explore and visualize data. However, due to the vast size of experimental datasets, researchers are increasingly using powerful, cloud-based systems to process and analyze data. These remote systems, called science gateways, offer user-friendly, Web-based access to high performance computing and storage resources, but typically lack interactive visualization capability. In this paper, we present BioViz Connect, a middleware Web application that links the CyVerse science gateway to the Integrated Genome Browser (IGB), a highly interactive native application implemented in Java that runs on the users personal computer. Using BioViz Connect, users can (i) stream data from the CyVerse data store into IGB for visualization, (ii) improve the IGB user experience for themselves and others by adding IGB specific metadata to CyVerse data files, including genome version and track appearance, and (iii) run compute-intensive visual analytics functions on CyVerse infrastructure to create new datasets for visualization in IGB or other applications. To demonstrate how BioViz Connect facilitates interactive data visualization, we describe an example RNA-Seq data analysis investigating how heat and desiccation stresses affect gene expression in the model plant Arabidopsis thaliana. Lastly, we discuss limitations of the technologies used and suggest opportunities for future work. BioViz Connect is available from https://bioviz.org.

bioinformatics↗