An Introduction to Functional Genomics and Systems Biology

Abstract

Objective: Over the past decade, the development of high-throughput technologies for DNA and protein analysis has revolutionized the ways in which cells can be studied. Within a relatively short time frame, research has changed from studying individual genes and proteins to analyzing entire genomes and proteomes.

Approach: In this article, we summarize the technologies and concepts that form the basis of this functional genomics approach.

Results: Microarray and next-generation sequencing technologies have allowed researchers to investigate many different aspects of the cell, including DNA mutations, histone modifications, DNA methylation, chromatin structure, transcription, and translation on a genome-wide level. In addition, mass spectrometry technologies have undergone significant development and currently enable us to globally profile protein levels, protein-protein interactions, post-translational protein modifications, and metabolites.

Innovation and conclusion: The integration of information from the various processes that occur within a cell provides a more complete picture of how genes give rise to biological functions, and will ultimately help us to understand the biology of organisms, in both health and disease.

Karine G. Le Roch, PhD

Figure 1.

Comparison between Sanger sequencing and next-generation sequencing (NGS) technologies. Sanger sequencing is limited to determining the order of one fragment of DNA per reaction, up to a maximum length of ∼700 bases. NGS platforms can sequence millions of DNA fragments in parallel in one reaction, yielding enormous amounts of data. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/wound

Figure 2.

Applications of NGS. The types of experiments that can be performed using NGS are many fold and are certainly not limited to the applications listed here. Applications include sequencing the complete genome or exome (all coding regions of the genome) to identify single-nucleotide polymorphisms (SNP-Seq) or other DNA mutations, profiling the genome-wide locations of methylated cytosines (Bisulfite-Seq), investigating various aspects of chromatin structure and regulation of gene expression by determining nucleosome positioning (MAINE-Seq and FAIRE-Seq), histone modifications or transcription factor binding (ChIP-Seq), and determining mRNA levels to study gene expression and its regulation (RNA-Seq). To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/wound

Figure 3.

Schematic overview of network analysis. Integration of information from different aspects of the cell, such as genome, transcriptome, proteome, interactome, and metabolome, will increase our understanding of how these components are interconnected and how these interactions determine biological functions. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/wound