Publications by authors named "Moustafa Ghanem"

10 Publications

  • Page 1 of 1

SIRT6 enhances oxidative phosphorylation in breast cancer and promotes mammary tumorigenesis in mice.

Cancer Metab 2021 Jan 22;9(1). Epub 2021 Jan 22.

Department of Internal Medicine and Medical Specialties (DIMI), University of Genoa, V.le Benedetto XV 6, 16132, Genoa, Italy.

Background: Sirtuin 6 (SIRT6) is a NAD-dependent deacetylase with key roles in cell metabolism. High SIRT6 expression is associated with adverse prognosis in breast cancer (BC) patients. However, the mechanisms through which SIRT6 exerts its pro-oncogenic effects in BC remain unclear. Here, we sought to define the role of SIRT6 in BC cell metabolism and in mouse polyoma middle T antigen (PyMT)-driven mammary tumors.

Methods: We evaluated the effect of a heterozygous deletion of Sirt6 on tumor latency and survival of mouse mammary tumor virus (MMTV)-PyMT mice. The effect of SIRT6 silencing on human BC cell growth was assessed in MDA-MB-231 xenografts. We also analyzed the effect of Sirt6 heterozygous deletion, of SIRT6 silencing, and of the overexpression of either wild-type (WT) or catalytically inactive (H133Y) SIRT6 on BC cell pyruvate dehydrogenase (PDH) expression and activity and oxidative phosphorylation (OXPHOS), including respiratory complex activity, ATP/AMP ratio, AMPK activation, and intracellular calcium concentration.

Results: The heterozygous Sirt6 deletion extended tumor latency and mouse survival in the MMTV-PyMT mouse BC model, while SIRT6 silencing slowed the growth of MDA-MB-231 BC cell xenografts. WT, but not catalytically inactive, SIRT6 enhanced PDH expression and activity, OXPHOS, and ATP/AMP ratio in MDA-MB-231 and MCF7 BC cells. Opposite effects were obtained by SIRT6 silencing, which also blunted the expression of genes encoding for respiratory chain proteins, such as UQCRFS1, COX5B, NDUFB8, and UQCRC2, and increased AMPK activation in BC cells. In addition, SIRT6 overexpression increased, while SIRT6 silencing reduced, intracellular calcium concentration in MDA-MB-231 cells. Consistent with these findings, the heterozygous Sirt6 deletion reduced the expression of OXPHOS-related genes, the activity of respiratory complexes, and the ATP/AMP ratio in tumors isolated from MMTV-PyMT mice.

Conclusions: Via its enzymatic activity, SIRT6 enhances PDH expression and activity, OXPHOS, ATP/AMP ratio, and intracellular calcium concentration, while reducing AMPK activation, in BC cells. Thus, overall, SIRT6 inhibition appears as a viable strategy for preventing or treating BC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-021-00240-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821730PMC
January 2021

A cloud-based data network approach for translational cancer research.

Adv Exp Med Biol 2015 ;820:229-38

Cancer Research UK Manchester Institute, University of Manchester, Manchester, M20 4BX, UK,

We develop a new model and associated technology for constructing and managing self-organizing data to support translational cancer research studies. We employ a semantic content network approach to address the challenges of managing cancer research data. Such data is heterogeneous, large, decentralized, growing and continually being updated. Moreover, the data originates from different information sources that may be partially overlapping, creating redundancies as well as contradictions and inconsistencies. Building on the advantages of elasticity of cloud computing, we deploy the cancer data networks on top of the CELAR Cloud platform to enable more effective processing and analysis of Big cancer data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-3-319-09012-2_16DOI Listing
April 2015

WikiSensing: an online collaborative approach for sensor data management.

Sensors (Basel) 2012 Oct 1;12(10):13295-332. Epub 2012 Oct 1.

Department of Computer Science, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.

This paper presents a new methodology for collaborative sensor data management known as WikiSensing. It is a novel approach that incorporates online collaboration with sensor data management. We introduce the work on this research by describing the motivation and challenges of designing and developing an online collaborative sensor data management system. This is followed by a brief survey on popular sensor data management and online collaborative systems. We then present the architecture for WikiSensing highlighting its main components and features. Several example scenarios are described to present the functionality of the system. We evaluate the approach by investigating the performance of aggregate queries and the scalability of the system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s121013295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3545568PMC
October 2012

Tavaxy: integrating Taverna and Galaxy workflows with cloud computing support.

BMC Bioinformatics 2012 May 4;13:77. Epub 2012 May 4.

Center for Informatics Sciences, Nile University, Giza, Egypt.

Background: Over the past decade the workflow system paradigm has evolved as an efficient and user-friendly approach for developing complex bioinformatics applications. Two popular workflow systems that have gained acceptance by the bioinformatics community are Taverna and Galaxy. Each system has a large user-base and supports an ever-growing repository of application workflows. However, workflows developed for one system cannot be imported and executed easily on the other. The lack of interoperability is due to differences in the models of computation, workflow languages, and architectures of both systems. This lack of interoperability limits sharing of workflows between the user communities and leads to duplication of development efforts.

Results: In this paper, we present Tavaxy, a stand-alone system for creating and executing workflows based on using an extensible set of re-usable workflow patterns. Tavaxy offers a set of new features that simplify and enhance the development of sequence analysis applications: It allows the integration of existing Taverna and Galaxy workflows in a single environment, and supports the use of cloud computing capabilities. The integration of existing Taverna and Galaxy workflows is supported seamlessly at both run-time and design-time levels, based on the concepts of hierarchical workflows and workflow patterns. The use of cloud computing in Tavaxy is flexible, where the users can either instantiate the whole system on the cloud, or delegate the execution of certain sub-workflows to the cloud infrastructure.

Conclusions: Tavaxy reduces the workflow development cycle by introducing the use of workflow patterns to simplify workflow creation. It enables the re-use and integration of existing (sub-) workflows from Taverna and Galaxy, and allows the creation of hybrid workflows. Its additional features exploit recent advances in high performance cloud computing to cope with the increasing data size and complexity of analysis.The system can be accessed either through a cloud-enabled web-interface or downloaded and installed to run within the user's local environment. All resources related to Tavaxy are available at http://www.tavaxy.org.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2105-13-77DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583125PMC
May 2012

The design and implementation of a workflow analysis tool.

Philos Trans A Math Phys Eng Sci 2010 Sep;368(1926):4193-208

Department of Computing, Imperial College London, 180 Queen's Gate, London SW7 2AZ, UK.

Motivated by the use of scientific workflows as a user-oriented mechanism for building executable scientific data integration and analysis applications, this article introduces a framework and a set of associated methods for analysing the execution properties of scientific workflows. Our framework uses a number of formal modelling techniques to characterize the process and data behaviour of workflows and workflow components and to reason about their functional and execution properties. We use the framework to design the architecture of a customizable tool that can be used to analyse the key execution properties of scientific workflows at authoring stage. Our design is generic and can be applied to a wide variety of scientific workflow languages and systems, and is evaluated by building a prototype of the tool for the Discovery Net system. We demonstrate and discuss the utility of the framework and tool using workflows from a real-world medical informatics study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1098/rsta.2010.0157DOI Listing
September 2010

DockFlow - a prototypic PharmaGrid for virtual screening integrating four different docking tools.

Stud Health Technol Inform 2009 ;147:3-12

Fraunhofer-Institute for Algorithms and Scientific Computing , Schloss Birlinghoven, 53754 Sankt Augustin, Germany.

In this paper we present DockFlow, a prototypic version of a PharmaGrid. DockFlow is supporting pharmaceutical research through enabling virtual screening on the Grid. The system was developed in the course of the BRIDGE project funded by the European Commission. Grids have been used before to run compute- and data-intensive virtual screening experiments, like in the WISDOM project. With DockFlow, however, we addressed a variety of problems yet unsolved, like the diversity of results produced by different docking tools. We also addressed the problem of analysing the data produced in a distributed virtual screening system applying a combinatorial docking approach. In DockFlow we worked on a grid-based problem solving environment for virtual screening with the following major features: execution of four different docking services (FlexX, AutoDock, DOCK and GAsDock) at locations in Europe and China remotely from a common workflow, storage of the results in a common Docking Database providing a shared analysis platform for the collaboration partners and combination of the results. The DockFlow prototype is evaluated on two scientific case studies: malaria and avian flu.
View Article and Find Full Text PDF

Download full-text PDF

Source
September 2009

Air Pollution Monitoring and Mining Based on Sensor Grid in London.

Sensors (Basel) 2008 Jun 1;8(6):3601-3623. Epub 2008 Jun 1.

Department of Physics, Imperial College London, 180 Queens Gate, London SW7 2BW, UK.

In this paper, we present a distributed infrastructure based on wireless sensors network and Grid computing technology for air pollution monitoring and mining, which aims to develop low-cost and ubiquitous sensor networks to collect real-time, large scale and comprehensive environmental data from road traffic emissions for air pollution monitoring in urban environment. The main informatics challenges in respect to constructing the high-throughput sensor Grid are discussed in this paper. We present a twolayer network framework, a P2P e-Science Grid architecture, and the distributed data mining algorithm as the solutions to address the challenges. We simulated the system in TinyOS to examine the operation of each sensor as well as the networking performance. We also present the distributed data mining result to examine the effectiveness of the algorithm.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s80603601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3714656PMC
June 2008

Web services in the life sciences.

Drug Discov Today 2005 Jun;10(12):865-71

Department of Computing, Imperial College, 180 Queen's Gate, London, UK, SW7 2AZ.

Web services provide a standard way of publishing applications and data sources over the internet, enabling mass dissemination of knowledge. In the life sciences, the web-service approach is seen as being a road to standardizing the multitude of tools available from different providers. In this article, we present an overview of the technology (focusing on life-science applications), we list the currently available service providers and we discuss advanced issues raised by the concept.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1359-6446(05)03481-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185667PMC
June 2005

Glow discharge in microfluidic chips for visible analog computing.

Lab Chip 2002 May 29;2(2):113-6. Epub 2002 Apr 29.

Department of Chemistry, Imperial College of Science, Technology and Medicine, London, UKSW7 2AY.

Here we present a novel visible analog computing approach for solving a wide class of shortest path problems. Using a microfluidic chip for computation, based on the lighting up of a glow discharge, the solution to maze search problems, the solution of a network shortest path and k-shortest paths problems and the practical application of finding the shortest paths between several landmarks from a street map are presented. The solution and visible display (in real time) for these problems shows only a small difference in practical problem solving time among problems with varying differences in size.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/b200589aDOI Listing
May 2002

The discovery net system for high throughput bioinformatics.

Bioinformatics 2003 ;19 Suppl 1:i225-31

Department of Computing Imperial College, 180 Queens Gate, London, SW7 2RH, UK.

Motivation: Bioinformatics requires Grid technologies and protocols to build high performance applications without focusing on the low level detail of how the individual Grid components operate.

Results: The Discovery Net system is a middleware that allows service developers to integrate tools based on existing and emerging Grid standards such as web services. Once integrated, these tools can be used to compose reusable workflows using these services that can later be deployed as new services for others to use. Using the Discovery Net system and a range of different bioinformatics tools, we built a Grid based application for Genome Annotation. This includes workflows for automatic nucleotide annotation, annotation of predicted proteins and text analysis based on metabolic profiles and text analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/bioinformatics/btg1031DOI Listing
October 2004