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The Bioinformatics Revolution

Over the next few years, there will be changes in all of the sciences grouped around molecular biology

Eduardo Geraque

Throughout history the areas of biology have undergone various revolutions. Be it with the research of Charles Darwin (1809-1882), in the 19th century, or with the discovery of the double helix some fifty years ago, many of these revolutionary novelties have been incorporated into the routine of the laboratories that study life. During the past decade, before this new century and the millennium that ended, another revolutionary wave appeared. Genomic research, who have investigated from the DNA of man to those of bacteria, have transformed forever some areas of biology. Over the next few years, these transformations are going to radiate and reach all the sciences that gravitate around molecular biology.

“We could make an analogy of this current moment to that which occurred at the end of the 70s, beginning of the 80s”, Sandro de Souza, the bioinformatics coordinator at the Sao Paulo Ludwig Institute, an entity linked to the Cancer Hospital, explains. For the bioinformatician, who works with the analysis of human DNA sequences, in the same way that more than twenty years ago molecular biology became part of the routine of almost all biology laboratories in the world, the same thing that will happen with bioinformatics in the very near future. “Now there has been a cultural change. Shortly, every laboratory is going to have somebody carrying out research using bioinformatics”, the scientist suggested.

For him, one of the major consequences of the start of the genomics era is in the vision change of biologists in relation to the areas of statistics and information technology. “Their way of thinking changed completely with the genome projects”, Souza explains. “The volume of data generated and the possible happenings in research in the future are enormous. Bioinformatics, at least in the bio-medicinal area, is on a path without return.” This super evaluation of bioinformatics is not an exaggeration. Starting in 1995, the methodology tools elaborated for this area of knowledge were essential for the success of the genome projects developed in Brazil and the world.

For example, the conclusion of the human genome sequencing had its time reduced by almost five years. In Brazil the bioinformatics group put together to make up the ONSA (Organization for Nucleotide Sequencing and Analysis) network also played a decisive role so that the emblematic sequencing of theXylella fastidiosa bacterium (a study that merited the front cover of the magazineNature on the 13th of July 2000) would be victorious. In the tender for theXylella project there was an opening for a bioinformatics laboratory. Unicamp ended up being the winner.

At the head of the institution?s bioinformatics laboratory were the young scientists João Setubal and João Meidanis. One other João, João Kitajima also made up part of the team. They weren?t dealing with just receiving pieces of sequenced DNA, putting them into the computer program and then they were finished. As well as refining the methodology techniques, those only informal at that time, they had even to approximate their work routines to those of the molecular biologists. This new routine that transformed the lives of the information technology scientists who participated in the Genome Project also only sprang up because there was scientific courage.

If it had depended on one of the international consultants chosen by FAPESP to make up the international scientific committee for theXylella project, all of the work on bioinformatics would have been carried out abroad. For André Goffeau, the French scientist who coordinated the sequencing of the genome of yeast, completed during 1996, at that time it would have been better to hire a European specialist to deal with the bioinformatics of theXylella sequencing. He knew a number of them, since in the end, the yeast project had brought together one hundred European laboratories.

Yet again, the Brazilian leaders decided to bet their bets on the national workforce and were not disappointed. Even Goffeau himself also recognized the merit of Brazil in this area when the project was concluded in 2000. All of this revolution caused by the start of the genomic era, and in which Brazil has had a fundamental role, at least in the cases of the projects in the agricultural area, is much closer to the beginning than to the end.

It is as if oceanography only managed to study the first ten meters of the column of water that makes up the ocean. “If we imagined an inverted pyramid, the sequencing of DNA and the proteins are only the very tip of this figure”, João Setubal, from Unicamp?s Computer Institute, underlines. In spite of the fact that within this same phase some methodology problems still exist, often because of the complexity of the object studied such as is the case with the human genome, a new phase within bioinformatics is also taking place. “As we move on towards the top of this inverted pyramid a second stage is the study of the interaction between the molecules of a single cell”, Setubal says. Research known as “proteome studies” are inserted in this part of the hypothetical pyramid of bioinformatics.

“At no point will the new tools and the new techniques of bioinformatics exclude those of the past. These new pathways will work in parallel. The new doesn?t remove the importance of the old”, the Unicamp scientist emphasizes. In this constant evolution of both informatics and genomics, the interaction between biologists and information technology experts, (informaticians), as the projects developed through the ONSA network clearly showed, seem to be a short-cut towards new discoveries.

“New tools depend on an intense closeness between the areas of computing and biology, involving the researchers to the maximum”, João Meidanis from Unicamp, says. The scientist, who besides continuing at the university, is also working with his own bioinformatics company called Scylla, makes use of once again the lessons from the first genetic sequencings in order to analyze the present moment. “During the genome projects the personnel in Unicamp?s informatics laboratory would blend in completely with their biology colleagues.

Not all of the new researchers, who have recently come into this field have made a point of making this type of relationship close. The biologists resent that.” The other side of the coin, as Meidanis says, also exists. “Some say that we are spoiling the biologists, as we give everything for free to them. And now a mood has been created that this is really to be given for free.” In spite of this lack of harmony in some cases, the scientist from Scylla himself recognizes that new tools are being created in bioinformatics.

The Cage Project (Cooperation for Analysis of Gene Expression), of the Chemical Institute of USP, has already presented some interesting results.” Until the base is reached ? which in truth will be the pinnacle of the process ? of the pyramid proposed by Setubal, five other levels will have to have been conquered. This shows only that the path to be followed, both in bioinformatics and in molecular biology, is still infinitely long. “We are now entering into the phase of studying the functioning of the structures within a single cell”, Setúbal explains.

The natural evolution of research has still to reach the analysis of the cell of a tissue or of an organism, before having as its objective of study a complete individual. And afterwards, Setubal continues, there will be a demand that populations and the biosphere as a unit in itself be investigated through genomics. Possibly, when this distant future has arrived, there will be somebody who will make use of the term biology computing systems to substitute what today is conventionally called bioinformatics.

This path has presented many obstacles in the past and will continue in the future. In spite of the fact that genetic sequencing has become routine in various laboratories in Sao Paulo and Brazil, after terrible difficulties with the initial processes, some methodology limitations have still not been overcome, even at the world level. “For example, the sequencing of the human genome is ready, but nobody knows for certain how many genes it contains.

It was only possible to arrive at an approximation of thirty thousand”, Setubal states. Even with the lack of this information, the data generated through the sequencing of man?s DNA can already be used to advance genomic research. “This problem of the number of genes occurs because the human genome is extremely complex. It is not something simple in spite of all the efficient techniques that we have today to find these genes”, explains Sandro de Souza, the scientist who has on his curriculum participation in the invention of the ORESTES method (Open Reading frames EST Sequences) for genetic sequencing.

It is exactly because of the other forms of analysis of strips of DNA, even without knowing the correct number of genes of the human being, that this work of genetic sequencing not only set off the genomic revolution of the 90s, but as also proved to be a very high level of use for man himself. Signs coming from the national territory that this revolution is being consolidated are the centers of bioinformatics that are being formed in various regions of the country. According to Meidanis, besides the now traditional centers of São Paulo research (Unicamp, USP, Unesp and the Ludwig Institute), new centers can be cited. “People are being trained at various places.

Also, post-graduate courses have been created and, in some places there are new nuclei such as at the LNCC (National Scientific Computing Laboratory of Petrópolis, RJ), at Federal Universities of the states of Rio Grande do Sul -UFRGS, Pernambuco- UFPE and in Minas Gerais at UFMG. During the month of May, the realization of the First Brazilian Bioinformatics Congress will be an opportunity for the scientists in the area to update their knowledge and results in the country of this segment. The huge demand for professionals in bioinformatics is an indicator on its own that shows the increase of projects in this area.

If the current problem in some places is the lack of personnel to teach these new skills, in the very near future another different question might have to be solved. Making places for all of the bioinformaticians could very shortly be a challenge. One of the paths to solve this problem has already begun to get on track, through the very scientists who have developed this area in Brazil.

While Setubal helped in the foundation of the biotechnological company Alellyx, but today has returned to dedicating himself exclusively to the university, Meidanis continues to want to achieve his goals also in business. “We believe that all of society is going to benefit from the transmission of the huge amount of knowledge generated through the genome projects to companies. But the fight is arduous. First because it is something new and secondly because many companies in this area in Brazil are multinational and they carry out their research abroad”, Meidanis warns. For him, the few companies that decide to invest in this field should be partners in the process in which science looks indirectly to give impulse to the national economy.

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