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Genomics

 

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microRNA: Small RNA molecules of great utility as diagnostic biomarkers in lung cancer

18 April 2013 | By Michela A. Denti and Margherita Grasso, Laboratory of RNA Biology and Biotechnology, Centre for Integrative Biology, University of Trento, Mattia Barbareschi and Chiara Cantaloni, Unit of Surgical Pathology, Santa Chiara Hospital

In 1993, the laboratories of Victor Ambros and Gary Ruvkun, studying the larval development of the nematode Caenorhabditis elegans, found a small RNA molecule (22 nucleotides) which regulated the translation of the lin-14 gene in an unusual way1,2. They observed that the sequence of the tiny lin-4 RNA was complementary…

Figure 2: The number of targets addressed for a specific cancer patient. There are 90 currently approved anti-neoplastic drugs, including 9 biologicals2; a patient often receives a chemotherapy regimen comprising three to six chemotherapy agents and a targeted monoclonal antibody (left). A tumour has ~50 immunogenic antigens from protein-changing cancer mutations18,19 and 20-150 gene isoforms with tumour-enhanced expression that, assuming at least one immunogenic epitope per gene, suggests ~50 addressable expression and differentiation antigens (right)
Figure 2: The number of targets addressed for a specific cancer patient. There are 90 currently approved anti-neoplastic drugs, including 9 biologicals2; a patient often receives a chemotherapy regimen comprising three to six chemotherapy agents and a targeted monoclonal antibody (left). A tumour has ~50 immunogenic antigens from protein-changing cancer mutations18,19 and 20-150 gene isoforms with tumour-enhanced expression that, assuming at least one immunogenic epitope per gene, suggests ~50 addressable expression and differentiation antigens (right)
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The T cell druggable genome

3 September 2012 | By Jan Diekmann, Martin Löwer, John C. Castle, Sebastian Kreiter, Özlem Türeci and Ugur Sahin, Translational Oncology, Johannes Gutenberg Medical University of Mainz

The ‘druggable genome’ has been defined as those genes that can be pharmaceutically modulated; when intersected with disease-associated genes, the resultant set represents therapeutic targets for developing drugs to prevent and treat diseases. Historically, druggable therapeutic target genes have been defined by two features; (i) their significant contribution to the…

Figure 1 Schematic illustration of arrayed or pooled RNAi screens in cells. Left panel. Pooled-viral vectors encoding libraries of shRNAs targeting multiple genes can be used to transduce a target cell population in a single tissue culture dish. After selection for the desired phenotype, cells are analysed for the identification of genes whose inhibition by RNAi knockdown cause the specific phenotype as described in Table 1. The relative abundance of each shRNA or a random 60-mer barcode expressed from the same vector as the specific shRNA can be identified and quantified by labelling the PCR product with fluorescent dyes (e.g., Cy5 or Cy3). The PCR products are then hybridised to custom designed cDNA microarrays containing barcode or shRNA complementary oligonucleotides. The relative abundance of barcodes obtained from the cells that were exposed to selective pressure are compared to that detected in control cells that have been exposed to the same shRNA library, but not to the selective pressure (for example, drug treatment or genetic mutations). Right panel. Arrayed RNAi screen libraries consist of individual siRNA or shRNA reagents that target different genes and that are placed in each well of a multi-well plate. RNAi reagent libraries can comprise synthetic siRNAs, plasmid-or virally-encoded shRNAs. Various assay readouts are used to determine the effect of RNAi on the phenotype as described in Table 1. Adapted10.
Figure 1 Schematic illustration of arrayed or pooled RNAi screens in cells. Left panel. Pooled-viral vectors encoding libraries of shRNAs targeting multiple genes can be used to transduce a target cell population in a single tissue culture dish. After selection for the desired phenotype, cells are analysed for the identification of genes whose inhibition by RNAi knockdown cause the specific phenotype as described in Table 1. The relative abundance of each shRNA or a random 60-mer barcode expressed from the same vector as the specific shRNA can be identified and quantified by labelling the PCR product with fluorescent dyes (e.g., Cy5 or Cy3). The PCR products are then hybridised to custom designed cDNA microarrays containing barcode or shRNA complementary oligonucleotides. The relative abundance of barcodes obtained from the cells that were exposed to selective pressure are compared to that detected in control cells that have been exposed to the same shRNA library, but not to the selective pressure (for example, drug treatment or genetic mutations). Right panel. Arrayed RNAi screen libraries consist of individual siRNA or shRNA reagents that target different genes and that are placed in each well of a multi-well plate. RNAi reagent libraries can comprise synthetic siRNAs, plasmid-or virally-encoded shRNAs. Various assay readouts are used to determine the effect of RNAi on the phenotype as described in Table 1. Adapted10.
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RNAi screens for the identification and validation of novel targets: Current status and challenges

16 December 2010 | By Attila A. Seyhan, Translational Immunology, Inflammation and Immunology, Pfizer Pharmaceuticals

Recent advances in RNA interference (RNAi) technology and availability of RNAi libraries in various formats and genome coverage have impacted the direction and speed of drug target discovery and validation efforts. After the introduction of RNAi inducing reaagent libraries in various formats, systematic functional genome screens have been performed to…

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Functional genomics as a tool for guiding personalised cancer treatment

29 October 2010 | By Roderick Beijersbergen, Group Leader Molecular Carcinogenesis, the Netherlands Cancer Institute

Improved understanding of the molecular alterations in cancer cells has fuelled the development of more specific and directed cancer therapies. However, it has become clear that response rates can be low due to confounding genetic alterations that render these highly specific therapies ineffective. As a result, the costs of cancer…

Figure 1 Advances in the development of sequencing technologies have resulted in an increase in data output with a dramatic decrease in cost. This graph compares calculated sequencing costs for one complete haploid human genome sequence (23 chromosomes, three billion bases) * estimated from literature ** marketing figures
Figure 1 Advances in the development of sequencing technologies have resulted in an increase in data output with a dramatic decrease in cost. This graph compares calculated sequencing costs for one complete haploid human genome sequence (23 chromosomes, three billion bases) * estimated from literature ** marketing figures
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The Sequencing Revolution: enabling personal genomics and personalised medicine

29 October 2010 | By Bhupinder Bhullar, Novartis Institute for Biomedical Research

It has been 10 years since the completion of the first draft of the human genome. Today, we are in the midst of a full assault on the human genetic code, racing to uncover the genetic mechanisms that affect disease, aging, happiness, violence ... and just about every imaginable human…

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Digital polymerase chain reaction; new diagnostic opportunities

22 February 2010 | By

LGC is an international science-based company located in South West London. A progressive and innovative enterprise, LGC operates in socially responsible fields underpinning the health, safety and security of the public, and regulation and enforcement for UK government departments and blue chip clients. Our products and services enable our customers…

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What the future holds for real-time PCR

10 January 2009 | By

TATAA Biocenters, located in Gothenburg, Sweden, Prague, Czech Republic, Freising outside Münich in Germany, and Sunnyvale, California1, work with leading instrument manufacturers and reagents companies in the quantitative real-time PCR (qPCR) field on new applications, making the know-how available through hands-on courses worldwide. Every year new courses are launched based…

DNA strands
DNA strands
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Computational prediction of microRNA and targets

29 September 2008 | By Russell Grocock, Principle Bioinformatics Scientist, GSK

MicroRNAs (miRNAs) are small (~21nucleotides), evolutionarily conserved, noncoding RNA molecules that regulate gene expression1. In mammalian genomes, conservative predictions suggest that between 500-1500 miRNAs exist. There miRNAs appear to be capable of regulating the expression of multiple genes, with many genes appearing to be regulated by multiple, different, miRNAs2. Less…

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Genomics for the new biomedicine

7 April 2008 | By

One of the most profound advances in biology and medicine has been the sequencing of entire genomes, including the human genome. The end product was the availability of the complete genetic blue print of organisms of importance to medicine and biotechnology. This changed how we conducted science. Cloning individual genes…