Genomic Technnologies for Drug Discovery

From the current knowledge of genomics, at least 500 targets are available for drug therapy. Opportunities provided by genomics include the potential for developing treatments for 100 of the most important multifactorial diseases with 500–1000 disease-related genes and 3000–10 000 new drug targets. Genomic technologies are built on basic tools of biotechnology. Functional genomics represents a new phase of genome analysis, i.e. function of genes. It is characterised by highthroughput or large-scale experimental methods combined with statistical
and computational analysis of the results. The fundamental strategy in a functional genomics approach is to expand the scope of biological investigation from studying single genes or proteins to studying all genes or proteins at once in a systematic fashion.
1. SNPs in Drug Discovery
The study of single nucleotide polymorphisms (SNPs) is crucial for characterising molecular targets and can also validate the role of these targets in disease. SNPs are important in the development of new pharmaceuticals with impact in the following areas:
- Target identification. Positional cloning looks for disease-susceptibility genes near markers that have an inheritance pattern similar to that of the disease. SNPs are used as simple genetic markers.

- Target characterisation. The degree of genetic variation within a target is important because it can alter gene function and influence drug interaction. Because modern methods of drug discovery involve high-throughput screening of large chemical libraries produced by combinatorial chemistry, it is important that the target of the screen is representative of the majority of the target population. This is even more important when SNPs affect the amino acid
structure and function of the protein. Although drug targets are screened at nucleic acid level to determine their degree of genetic variation, identification of the variants may be inadequate and
bioinformatic support is necessary.
-Target validation. There is an abundance of drug targets available but many have no clue as to their role in disease. Genetic epidemiology can be used to show the functional involvement of a particulardrug target in the disease of  interest. This approach can also be used to identify new therapeutic targets for existing drugs.

-Pharmacogenetics. This is the study of how genetic variations affect drug response and metabolism. Polymorphisms in enzymes that metabolise drugs are also responsible for unexpected adverse effects of normal doses of drugs. This information is now used for the
development of personalised medicines.
- Pharmacogenomics. This term implies the use of genetic sequence and genomics information in patient management to enable therapy decisions to be made. The genetic sequence and genomics information can be that of the host (normal or diseased) or of the pathogen. Pharmacogenomics will have an impact on all phases of drug development  from drug discovery to clinical trials. Pharmacogenomics is an important basis for the development of
personalised medicines.
2. Gene Expression Profiling
Analysis of gene-expression patterns derived from large expressed sequence tag (EST) databases has become a valuable tool in the discovery of therapeutic targets and diagnostic markers. Sequence data derived from a wide variety of cDNA libraries offer a wealth of information for identifying genes for pharmaceutical product development.
Collecting, storing, organising, analysing and presenting cDNA expression data require advanced bioinformatics methods and highperformance computational equipment. Comparison of expression patterns from normal and diseased tissues enables inferences about gene function to be made and medically relevant genes as candidates for therapeutics research and drug discovery.
3. Limitations of Genomics for Drug Discovery and Need for Other Omics
Although useful, DNA sequence analysis alone does not lead efficiently to new target identification, because one cannot easily infer the functions of gene products or proteins and protein pathways from a DNA sequence. It has become obvious that analysing genome sequences alone will not lead to new therapies for human diseases. Rather, an understanding of protein function within the context of complex cellular networks will be required to facilitate the discovery of novel drug targets and, subsequently, new therapies directed against them.
Functional genomics and proteomics have provided a huge amount of new drug targets. High-throughput screening and compound libraries produced by combinatorial chemistry have increased the number of new lead compounds. The challenge is to increase the efficiency of testing lead efficacy and toxicity. The traditional methods of toxicity testing in laboratory animals using haematological, clinical chemistry and histological parameters are inadequate to cope with this challenge. Gene and protein expression studies following treatment with drugs have shown that it is possible to identify changes in biochemical pathways that are related to a drug’s efficacy and toxicity and precede tissue changes. The patterns of these changes can be used as efficacy or toxicity markers in high-throughput screening assay. Several other omics technologies play an important role in drug discovery. Notable among these are proteomics and metabolomics.