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

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

A role for proapoptotic Bax and Bak in T-cell differentiation and transformation

Proapoptotic Bax and Bak are the key B-cell lymphoma-2 family members mediating apoptosis through the intrinsic pathway. Cells doubly deficient for Bax and Bak are profoundly resistant to apoptotic stimuli originating from multiple stimuli. Here we describe mice in which Bax and Bak have been deleted specifically in T-cells using Lck-Cre. In these T cell–specific BaxBak-deficient mice, early T-cell progenitors accumulate in the thymus, with relative depletion of more mature T cells. In addition, bone marrow progenitor cells fail to progress to the double positive stage when cultured on OP9 stromal cells expressing the Notch ligand Delta-like 1, consistent with a critical role for Bax and Bak in early T-cell development. Over time, T cell–specific BaxBak-deficient mice progress to an aggressive T-cell lymphoblastic leukemia/lymphoma. Interestingly, quantitative real-time polymerase chain reaction analysis of BaxBak-deficient T-cell lymphomas does not display amplification of the Notch signal transduction pathway, commonly activated in T-cell leukemia in both mouse and man. Bax and Bak, key regulators of the intrinsic pathway of apoptosis, are thus required to prevent T-cell malignancy, and for normal T-cell differentiation, regulating early T-cell development at the stage of early T-lineage progenitor cells