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Target Discovery (target + discovery)

Distribution by Scientific Domains
Chemistry57%
Medical Sciences42%

Selected Abstracts

Protein Kinase Target Discovery From Genome-Wide Messenger RNA Expression Profiling

MOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 4 2010
Avi Ma'ayan
Abstract Genome-wide messenger RNA profiling provides a snapshot of the global state of the cell under different experimental conditions such as diseased versus normal cellular states. However, because measurements are in the form of quantitative changes in messenger RNA levels, such experimental data does not provide direct understanding of the regulatory molecular mechanisms responsible for the observed changes. Identifying potential cell signaling regulatory mechanisms responsible for changes in gene expression under different experimental conditions or in different tissues has been the focus of many computational systems biology studies. Most popular approaches include promoter analysis, gene ontology, or pathway enrichment analysis, as well as reverse engineering of networks from messenger RNA expression data. Here we present a rational approach for identifying and ranking protein kinases that are likely responsible for observed changes in gene expression. By combining promoter analysis; data from various chromatin immunoprecipitation studies such as chromatin immunoprecipitation sequencing, chromatin immunoprecipitation coupled with paired-end ditag, and chromatin immunoprecipitation-on-chip; protein-protein interactions; and kinase-protein phosphorylation reactions collected from the literature, we can identify and rank candidate protein kinases for knock-down, or other types of functional validations, based on genome-wide changes in gene expression. We describe how protein kinase candidate identification and ranking can be made robust by cross-validation with phosphoproteomics data as well as through a literature-based text-mining approach. In conclusion, data integration can produce robust candidate rankings for understanding cell regulation through identification of protein kinases responsible for gene expression changes, and thus rapidly advancing drug target discovery and unraveling drug mechanisms of action. Mt Sinai J Med 77:345,349, 2010. © 2010 Mount Sinai School of Medicine [source]

Fault Diagnosis Engineering in Molecular Signaling Networks: An Overview and Applications in Target Discovery

CHEMISTRY & BIODIVERSITY, Issue 5 2010
Ali Abdi
Abstract Fault diagnosis engineering is a key component of modern industrial facilities and complex systems, and has gone through considerable developments in the past few decades. In this paper, the principles and concepts of molecular fault diagnosis engineering are reviewed. In this area, molecular intracellular networks are considered as complex systems that may fail to function, due to the presence of some faulty molecules. Dysfunction of the system due to the presence of a single or multiple molecules can ultimately lead to the transition from the normal state to the disease state. It is the goal of molecular fault diagnosis engineering to identify the critical components of molecular networks, i.e., those whose dysfunction can interrupt the function of the entire network. The results of the fault analysis of several signaling networks are discussed, and possible connections of the findings with some complex human diseases are examined. Implications of molecular fault diagnosis engineering for target discovery and drug development are outlined as well. [source]

Chemical genetics: catalysing pathway exploration and new target discovery

JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 11 2007
Joshua I Armstrong
Abstract Chemical genetics couples the availability of diverse chemistry with the strengths of molecular genetics to dissect signalling pathways in complex organisms. Plant biology laboratories have integrated this approach into their repertoire for probing hormone signalling, physiology and pesticide mode of action. These studies have led to the discovery of compounds that regulate development and the response to environmental stress. Chemical genetics facilitates our understanding of genetic signalling pathways and offers a new approach to pest management and plant health by enabling the direct chemical modulation of plant defence signalling. Copyright © 2007 Society of Chemical Industry [source]

Protein Kinase Target Discovery From Genome-Wide Messenger RNA Expression Profiling

MOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 4 2010
Avi Ma'ayan
Abstract Genome-wide messenger RNA profiling provides a snapshot of the global state of the cell under different experimental conditions such as diseased versus normal cellular states. However, because measurements are in the form of quantitative changes in messenger RNA levels, such experimental data does not provide direct understanding of the regulatory molecular mechanisms responsible for the observed changes. Identifying potential cell signaling regulatory mechanisms responsible for changes in gene expression under different experimental conditions or in different tissues has been the focus of many computational systems biology studies. Most popular approaches include promoter analysis, gene ontology, or pathway enrichment analysis, as well as reverse engineering of networks from messenger RNA expression data. Here we present a rational approach for identifying and ranking protein kinases that are likely responsible for observed changes in gene expression. By combining promoter analysis; data from various chromatin immunoprecipitation studies such as chromatin immunoprecipitation sequencing, chromatin immunoprecipitation coupled with paired-end ditag, and chromatin immunoprecipitation-on-chip; protein-protein interactions; and kinase-protein phosphorylation reactions collected from the literature, we can identify and rank candidate protein kinases for knock-down, or other types of functional validations, based on genome-wide changes in gene expression. We describe how protein kinase candidate identification and ranking can be made robust by cross-validation with phosphoproteomics data as well as through a literature-based text-mining approach. In conclusion, data integration can produce robust candidate rankings for understanding cell regulation through identification of protein kinases responsible for gene expression changes, and thus rapidly advancing drug target discovery and unraveling drug mechanisms of action. Mt Sinai J Med 77:345,349, 2010. © 2010 Mount Sinai School of Medicine [source]

The emerging field of chemical genetics: potential applications for pesticide discovery

PEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 12 2007
Terence A Walsh
Abstract The use of small molecules to probe biological systems, generally described as ,chemical genetics', has grown considerably in the past 7 years, especially in areas related to human biology and therapeutics. This review describes some aspects of chemical genetics technologies that can be usefully applied to pesticide target discovery and lead generation. The chemical genetics approach (consisting of a phenotype screen, a chemical library and a robust target identification methodology) is compared with conventional and target-based screening. The outcomes of a chemical genetics approach are novel protein targets coupled with in vivo -active chemical ligands. The ,chemistry-first' paradigm of the chemical genetics approach can circumvent some of the obstacles that have emerged for the exploitation of novel but chemically unvalidated targets identified from genetic or genomic screens. Some of the advantages and challenges in using chemical genetics approaches are reviewed. Copyright © 2007 Society of Chemical Industry [source]

Therapeutic potential of RNA interference against cancer

CANCER SCIENCE, Issue 8 2006
Fumitaka Takeshita
One of the most dramatic events of the past 5 years in the field of molecular biology has been the discovery of RNA interference (RNAi). Although RNAi is an evolutionarily conserved phenomenon for sequence-specific gene silencing in mammalian cells, exogenous small interfering RNA (siRNA) and vector-based short hairpin RNA (shRNA) can also invoke RNAi responses. Both are now not only experimental tools for analyzing gene function but are expected to be excellent avenues for drug target discovery and the emerging class of gene medicine for targeting incurable diseases such as cancer. The success of cancer therapeutic use of RNAi relies on the development of safe and efficacious delivery systems that introduce siRNA and shRNA expression vectors into target tumor cells. For their delivery, a variety of strategies have been used, most of them based on traditional gene therapy delivery systems. In this review, we present siRNA delivery method strategies and discuss the potential of RNAi-based gene therapy in cancer treatment. (Cancer Sci 2006; 97: 689,696) [source]

Fault Diagnosis Engineering in Molecular Signaling Networks: An Overview and Applications in Target Discovery

CHEMISTRY & BIODIVERSITY, Issue 5 2010
Ali Abdi
Abstract Fault diagnosis engineering is a key component of modern industrial facilities and complex systems, and has gone through considerable developments in the past few decades. In this paper, the principles and concepts of molecular fault diagnosis engineering are reviewed. In this area, molecular intracellular networks are considered as complex systems that may fail to function, due to the presence of some faulty molecules. Dysfunction of the system due to the presence of a single or multiple molecules can ultimately lead to the transition from the normal state to the disease state. It is the goal of molecular fault diagnosis engineering to identify the critical components of molecular networks, i.e., those whose dysfunction can interrupt the function of the entire network. The results of the fault analysis of several signaling networks are discussed, and possible connections of the findings with some complex human diseases are examined. Implications of molecular fault diagnosis engineering for target discovery and drug development are outlined as well. [source]