Browsing by Author "Hawkins, Jared B."

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    Chemotaxis in Densely Populated Tissue Determines Germinal Center Anatomy and Cell Motility: A New Paradigm for the Development of Complex Tissues
    Hawkins, Jared B.; Jones, Mark T.; Plassmann, Paul E.; Thorley-Lawson, David A. (PLOS, 2011-12-01)
    Germinal centers (GCs) are complex dynamic structures that form within lymph nodes as an essential process in the humoral immune response. They represent a paradigm for studying the regulation of cell movement in the development of complex anatomical structures. We have developed a simulation of a modified cyclic re-entry model of GC dynamics which successfully employs chemotaxis to recapitulate the anatomy of the primary follicle and the development of a mature GC, including correctly structured mantle, dark and light zones. We then show that correct single cell movement dynamics (including persistent random walk and inter-zonal crossing) arise from this simulation as purely emergent properties. The major insight of our study is that chemotaxis can only achieve this when constrained by the known biological properties that cells are incompressible, exist in a densely packed environment, and must therefore compete for space. It is this interplay of chemotaxis and competition for limited space that generates all the complex and biologically accurate behaviors described here. Thus, from a single simple mechanism that is well documented in the biological literature, we can explain both higher level structure and single cell movement behaviors. To our knowledge this is the first GC model that is able to recapitulate both correctly detailed anatomy and single cell movement. This mechanism may have wide application for modeling other biological systems where cells undergo complex patterns of movement to produce defined anatomical structures with sharp tissue boundaries.
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    Scalable and cost-effective NGS genotyping in the cloud
    Souilmi, Yassine; Lancaster, Alex K.; Jung, Jae-Yoon; Rizzo, Ettore; Hawkins, Jared B.; Powles, Ryan; Amzazi, Saaïd; Ghazal, Hassan; Tonellato, Peter J.; Wall, Dennis P. (2015-10-15)
    Background While next-generation sequencing (NGS) costs have plummeted in recent years, cost and complexity of computation remain substantial barriers to the use of NGS in routine clinical care. The clinical potential of NGS will not be realized until robust and routine whole genome sequencing data can be accurately rendered to medically actionable reports within a time window of hours and at scales of economy in the 10’s of dollars. Results We take a step towards addressing this challenge, by using COSMOS, a cloud-enabled workflow management system, to develop GenomeKey, an NGS whole genome analysis workflow. COSMOS implements complex workflows making optimal use of high-performance compute clusters. Here we show that the Amazon Web Service (AWS) implementation of GenomeKey via COSMOS provides a fast, scalable, and cost-effective analysis of both public benchmarking and large-scale heterogeneous clinical NGS datasets. Conclusions Our systematic benchmarking reveals important new insights and considerations to produce clinical turn-around of whole genome analysis optimization and workflow management including strategic batching of individual genomes and efficient cluster resource configuration.