A case study for cloud based high throughput analysis of NGS data using the globus genomics system

AbstractNext generation sequencing (NGS) technologies produce massive amounts of data requiring a powerful computational infrastructure, high quality bioinformatics software, and skilled personnel to operate the tools. We present a case study of a practical solution to this data management and analysis challenge that simplifies terabyte scale data handling and provides advanced tools for NGS data analysis. These capabilities are implemented using the “Globus Genomics” system, which is an enhanced Galaxy workflow system made available as a service that offers users the capability to process and transfer data easily, reliably and quickly to address end-to-endNGS analysis requirements. The Globus Genomics system is built on Amazon's cloud computing infrastructure. The system takes advantage of elastic scaling of compute resources to run multiple workflows in parallel and it also helps meet the scale-out analysis needs of modern translational genomics research

Experiences Building Globus Genomics: A Next-Generation Sequencing Analysis Service using Galaxy, Globus, and Amazon Web Services

ABSTRACT We describe Globus Genomics, a system that we have developed for rapid analysis of large quantities of next-generation sequencing (NGS) genomic data. This system achieves a high degree of end-to-end automation that encompasses every stage of data analysis including initial data retrieval from remote sequencing centers or storage (via the Globus file transfer system); specification, configuration, and reuse of multi-step processing pipelines (via the Galaxy workflow system); creation of custom Amazon Machine Images and on-demand resource acquisition via a specialized elastic provisioner (on Amazon EC2); and efficient scheduling of these pipelines over many processors (via the HTCondor scheduler). The system allows biomedical researchers to perform rapid analysis of large NGS datasets in a fully automated manner, without software installation or a need for any local computing infrastructure. We report performance and cost results for some representative workloads

Murine Leukemias with Retroviral Insertions at Lmo2 Are Predictive of the Leukemias Induced in SCID-X1 Patients Following Retroviral Gene Therapy

Five X-linked severe combined immunodeficiency patients (SCID-X1) successfully treated with autologous bone marrow stem cells infected ex vivo with an IL2RG-containing retrovirus subsequently developed T-cell leukemia and four contained insertional mutations at LMO2. Genetic evidence also suggests a role for IL2RG in tumor formation, although this remains controversial. Here, we show that the genes and signaling pathways deregulated in murine leukemias with retroviral insertions at Lmo2 are similar to those deregulated in human leukemias with high LMO2 expression and are highly predictive of the leukemias induced in SCID-X1 patients. We also provide additional evidence supporting the notion that IL2RG and LMO2 cooperate in leukemia induction but are not sufficient and require additional cooperating mutations. The highly concordant nature of the genetic events giving rise to mouse and human leukemias with mutations at Lmo2 are an encouraging sign to those wanting to use mice to model human cancer and may help in designing safer methods for retroviral gene therapy

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

High-Level Methodologies for Test Generation and Logic Simulation

Coordinated Science Laboratory was formerly known as Control Systems LaboratorySemiconductor Research Corporation / 88-DP-109U of I OnlyRestricted to UIUC communit

High-Level Methodologies for Test Generation and Logic Simulation

Coordinated Science Laboratory was formerly known as Control Systems LaboratorySemiconductor Research Corporation / 88-DP-109U of I OnlyRestricted to UIUC communit

A Comparative Clinical Study of Shatavaryadi and Guduchyadi Churna on Rajonivrutti Avastha with special reference to Postmenopausal Syndrome

The menopause is permanent cessation of menstruation at the end of reproductive life due to loss of ovarian follicular activity. Shatavaryadi Churna and Guduchyadi Churna– both drugs are 6grams twice daily before meal with milk for 2 months in two groups has been given. Both are effective in the management of Postmenopausal Syndrome. Shatavaryadi Churna is more effective than Guduchyadi Churna in the management of Postmenopausal Syndrome but both are an effective, safe, promising and cost effective remedy. Vata-Pittashamaka, Rasayana, Dhatuvardhaka, Agnidipaka, Pachana, Medhya, Vedanasthapana, Hridya, Anidranash drug in Shatavaryadi Churna helped to deliver such promising results. Guduchyadi Churna had also delivered satisfactory results treating in Postmenopausal Syndrome due toits Tridoshahara & Vata-Kaphashamaka activity along with Rasayana, Dipana, Pachana, Dhatuvardhaka, Balya, Hridya, Nidrajanana, Medhya and Vedanasthapana properties. The age at menopause appears to be genetically determined and is unaffected by race, socioeconomic status, age at menarche, or number of prior ovulations. Factors that are toxic to the ovary often result in an earlier age of menopause; for e.g., who smoke experience an earlier menopause. Women who have had surgery on their ovaries, have had a hysterectomy, despite retention of their ovaries, may also experience early menopaus

Extranodal NK/T-cell lymphoma primarily presenting as two adjacent slowly growing skin nodules with prominent epidermotropism and CD30 expression, a case report and review of literature

Extranodal NK/T-cell lymphoma (NKTCL) is a rarely occurring non-Hodgkin lymphoma with predilection for the nasal cavity. Cutaneous involvement, rarely occurring and often aggressive in behavior, may present as nodular mass-forming lesions with or without ulceration. Histologically, lesions are characterized by an atypical dermal lymphoid infiltrate with angioinvasion and associated necrosis. Fortuitously, Epstein-Barr virus (EBV) infection, implicated in the pathogenesis of this entity, serves as a useful diagnostic marker (i.e. EBER in situ hybridization). We present a 54-year-old-man who initially presented with two ulcerations on the right lower leg which progressed despite antibiotic therapy. Histologic examination demonstrated dense lymphoid infiltrates exhibiting epidermotropism, angiocentricity and angioinvasion extending into the deep dermis. Immunohistochemical staining demonstrated expression of CD2, CD3, CD8, TIA-1, perforin, and granzyme-B, consistent with a cytotoxic T-cell phenotype. Additionally, CD56 was positive, confirming the presence of a coexistent NK cell phenotype. Testing also demonstrated significant CD30 expression, and molecular analysis was positive for TCR gene rearrangement. These findings, in conjunction with EBER in situ hybridization positivity, confirmed a diagnosis of extranodal NKTCL. We aim to increase awareness of this rarely occurring lymphoma with cutaneous involvement. CD30 expression in NKTCL raises the possibility of targeted treatment with brentuximab