In Silico Approaches to Mechanistic and Predictive Toxicology: An Introduction to Bioinformatics for Toxicologists

Abstract

Bioinformatics, or in silico biology, is a rapidly growing field that encompasses the theory and application of computational approaches to model, predict, and explain biological function at the molecular level. This information rich field requires new skills and new understanding of genome-scale studies in order to take advantage of the rapidly increasing amount of sequence, expression, and structure information in public and private databases. Toxicologists are poised to take advantage of the large public databases in an effort to decipher the molecular basis of toxicity. With the advent of high-throughput sequencing and computational methodologies, expressed sequences can be rapidly detected and quantitated in target tissues by database searching. Novel genes can also be isolated in silico, while their function can be predicted and characterized by virtue of sequence homology to other known proteins. Genomic DNA sequence data can be exploited to predict target genes and their modes of regulation, as well as identify susceptible genotypes based on single nucleotide polymorphism data. In addition, highly parallel gene expression profiling technologies will allow toxicologists to mine large databases of gene expression data to discover molecular biomarkers and other diagnostic and prognostic genes or expression profiles. This review serves to introduce to toxicologists the concepts of in silico biology most relevant to mechanistic and predictive toxicology, while highlighting the applicability of in silico methods using select examples.

KEYWORDS: :

• in silico
• bioinformatics
• toxicogenomics
• microarray
• cluster analysis
• expressed sequence tags
• SAGE
• position weight matrix
• ligand docking
• molecular modeling
• multiple sequence alignment
• BLAST
• single nucleotide polymorphisms.