Genomic Technologies for Systems Biology

Abstract

This chapter describes genomic technologies and explores their applications in systems biosciences. Technologies are based on the principles of base-pair hybridization and DNA polymerization, which leads to the tool set of genome-to-systems. The term "genome-to-systems" reflects the primary use of genomic information in systems analysis of biological processes. Each tool provides one or more aspects of systems biological information: quantitative assessment, precise component determination, and comprehensive coverage. The ability to assess the expression of all known gene transcripts in a quantitative fashion formed the basis for genome-wide systems analyses of biological processes. Sequencing is accomplished by using reverse transcriptase to convert the messenger RNA (mRNA) code into complementary DNA (cDNA). A second round of polymerization renders this single-stranded cDNA into a double-stranded entity that can be inserted into appropriate vectors and cloned. The three main DNA sequencing platforms are Roche 454 Life Sciences Genome Analyzer from Illumina, Sequencing by Oligonucleotide Ligation, and Detection (SOLiD). The collection of all transcripts in a cell or the transcriptome can be assessed by expression arrays or by direct sequencing approaches. An important means of understanding the biology of the candidate gene is through loss-of-function experiments. Sequencing of the human and mouse genomes established high gene-to-gene functional homology that displayed an organizational synteny along the chromosomes between the two species. When all factors are taken into account, RNAi strategies are among the most precise approaches to gene-targeted screening that are available. © 2010 Elsevier Inc. All rights reserved.