The Hindu Business Line : Try gene traps on bacteria

A Pune-based company claims its software can help speed up the process of identifying the essential genes in bacteria. These genes can then be targeted to destroy the bacteria.

THAT biotechnology is here to stay is no longer a point in dispute. And waking up to its potential, State Governments are setting up biotech parks. Maharashtra has earmarked huge areas for this purpose.

But why aren't things happening at a brisker pace? One possible reason could be the need for more indigenous R&D. And then, there's also the time factor. One needs breakthroughs before one runs out of funds.

And this is where the Pune-based Evolvus Biotech Pvt. Ltd believes it can help. The company has come up with software called ViaGene that will help pinpoint the essential genes in a bacterium. These genes can then be targeted to destroy the bacterium. The software uses machine-learning algorithms to identify the genes in a bacterium that are essential for its survival.

According to Dr Milind Watve, President, Evolvus, "it is like knowing where to shoot when you want to kill a person with a single bullet.''

Rajeev Gangal, Vice-President and co-founder of Evolvus, says knowledge about essential genes is otherwise obtained by laborious laboratory experiments called gene-knockout experiments that cost anywhere between $1 and $4 million per bacterial genome. ViaGene is available for the Windows NT4 and Windows 2000 platforms although the core of the software is portable and can be adapted for other popular operating systems, he says. The company has a predictive model of E.coli and models for Mycobacterium tuberculosis, Helicobacter pylori and Staphylococcus aureus are also on the way. Plans are also under way to support ViaGene with a curated database containing functionally-annotated essential genes.

What does ViaGene do? It predicts the essentiality of bacterial genes using a combination of DNA sequence descriptors and pattern-recognition methods. The target-identification time for an entire genome will be reduced to a few hours. This algorithm is of enormous importance in anti-microbial target selection and prioritisation, he says. The classification accuracy is 85 per cent for a training set and 80 per cent for a test set, he says.

Research studies indicate that the 10 most clinically important human pathogenic bacteria include approximately 1,500 to 6,000 genes. Initial genomic sequencing efforts have produced significant amounts of information that have the potential to have a profound effect on drug discovery and development. However, gene-sequence data alone may not provide sufficient information on the role of the gene in the organism. Knowledge of gene function is necessary to allow researchers to use sequence information to determine which genes are involved in disease and to develop therapeutic products to target those genes. The key concept, as stressed earlier, is identifying `essentiality' and the essential genes in pathogens that produce proteins required for growth and survival and therefore make ideal anti-microbial drug targets.

"We believe that approximately 5-10 per cent of the genes in bacterial genomes are essential and all known antibiotics prescribed today inhibit less than 25 different essential gene drug targets," says Gangal.

According to Gangal, the only methods available in both the public and proprietary domain are lab-based knockout/knockdown methods. These `essentiality' validating methods involve an investment of at least $200 per gene in E. coli and can go up to $1,000 per gene or more for organisms such as S. aureus and M. tuberculosis which are difficult pathogens to deal with in a lab setting. Thus the cost for information on `essential genes' per genome is extremely high. The time for a lab-based analysis might range from a few weeks to a couple of years, depending on the number of targets and organisms one is looking at.

He concedes that the software will not completely eliminate laboratory experiments. It will, however, help in locating a smaller set of genes prior to the knock-out experiments. "The difference is that between shooting in the dark to switching on the lights before shooting. ViaGene has already given us a list of genes in E. coli which are very likely to be essential about which there was no information," he says. The tool will aid molecular biologists in streamlining their efforts at prioritising anti-bacterial drug targets, he says.

According to Dr L. Arvind, staff scientist at the Computational Biology Branch of the National Institute of Health, Bethesda, US, "on the whole, the ViaGene software is an easy-to-use tool to predict the essentiality of a gene. Given its high frequency of correct calls, it can definitely be considered a useful tool for determining new bacterial targets for therapeutics." It may cut down on costs too, he says.

But it remains to be seen how many pharma companies in the Indian scene seek to integrate the software with their R&D.

rsavitha@hotmail.com

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