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ESI Special Topics, April 2005
Citing URL: http://www.esi-topics.com/erf/2005/april05-BjarneKnudsen.html

From •>>April 2005

Bjarne Knudsen answers a few questions about this month's emerging research front in field of Computer Science:

Computer Science
Article: RNA secondary structure prediction using stochastic context-free grammars and
evolutionary history
Authors: Knudsen, B;Hein, J
Journal: BIOINFORMATICS, 15: (6) 446-454, JUN 1999
Addresses: Aarhus Univ, Inst Biol Sci, Dept Ecol & Genet, Bldg 550, Ny Munkegade, DK-8000 Aarhus C, Denmark.
Aarhus Univ, Inst Biol Sci, Dept Ecol & Genet, DK-8000 Aarhus C, Denmark.


ST:  Why do you think your paper is highly cited?


“One of the most important aspects of this new RNA structure prediction method is that it utilizes an explicit model of sequence evolution.”

The paper deals with a new RNA secondary structure prediction method based on evolutionary analyses, which is in the interesting boundary region between computer science and biology. Classical computer science methods are used to help solve a problem of interest for molecular biologists. This results in a number of citations from both algorithmical and more applied papers. Another reason for our paper being highly cited is that it provides a web-based method for RNA analysis, which is easy to use, and thus fairly widespread.

ST:  Does it describe a new discovery or new methodology that's useful to others?

The method described has helped a number of scientists infer secondary structures for RNA molecules, leading to a new functional understanding. The method has, for example, aided in the determination of the RNA structure of the leader sequence in the HIV genome. The predicted structure has been experimentally verified by the research group of Jørgen Kjems at the University of Aarhus, Denmark. Present experimental work is focusing on the biological importance of these structures.

One of the most important aspects of this new RNA structure prediction method is that it utilizes an explicit model of sequence evolution. By applying this method, it becomes possible to make much more reliable predictions, due to the additional information which can be extracted from related sequences. Including evolutionary information in bioinformatical analyses is a promising approach, often leading to very good results. With the numerous genome projects being undertaken, this additional information is becoming easily available, and good algorithms for its usage are essential.

ST:  How did you become involved in this research?

Jotun Hein and I started developing the RNA structure prediction algorithms at the University of Aarhus in 1998, resulting in a theoretically oriented paper in the journal Bioinformatics in 1999 (15(6):446-454). The present paper improves and further evaluates the method. Our work was inspired by work on protein structure prediction done by Jeffrey Thorne, Nick Goldman, and David Jones in 1996.

Working in the research group of Jotun Hein was very inspiring, both due to his excellent scientific abilities and also because of the opportunity to work with the group he had assembled—a team which included biologists, molecular biologists, computer scientists, and statisticians. This provided a perfect combination of researchers for bioinformatics research since the field is quite diverse. At present, Jotun is a professor at the University of Oxford. The RNA paper was published while I was working at the University of Florida with Michael M. Miyamoto, where we continued to develop a wide range of bioinformatics algorithms.

At present, I am the chief scientific officer in a bioinformatics software and consulting company called CLC bio (www.clcbio.com). We aim to further develop the RNA structure-prediction algorithms, along with other algorithms for DNA, RNA, and protein analysis. One of our main interests and challenges is to produce user-friendly software, making the advanced algorithms available to general molecular biologists and biochemists

ST:  Could you summarize the significance of your paper in layman's terms?

Chemically, RNA molecules closely resemble DNA, but their biological roles differ significantly. DNA is exclusively used to store information, while most biological functions are undertaken by proteins. RNA has an intermediate role, both participating in the storage and transfer of information and in more directly functional roles.

RNA is involved in a number of the most fundamental cellular processes, including the whole machinery involved in reading the information from DNA sequences and building the encoded proteins. This central role of RNA has led researchers to suggest that RNA may have formed the basis of early life on Earth, before DNA and proteins were used by biological systems.

The function of an RNA molecule is tightly linked to its structure. The biological importance of RNA has of course led many scientists to study the structure and function in great detail. It is, however, a very time-consuming process to experimentally determine the structure. Thus, computational methods, including the one in our paper, have proven very useful in making this research more focused and efficient.End

Bjarne Knudsen
Chief Scientific Officer
CLC bio A/S
Aarhus, Denmark

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ESI Special Topics, April 2005
Citing URL: http://www.esi-topics.com/erf/2005/april05-BjarneKnudsen.html

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