Computer power helps solve biological puzzles
Robots in biology laboratories have lifted the burden of ‘grunt work’ from researchers. With inhuman speed, they process thousands of samples trying to find genetic markers that indicate susceptibility to disease. Automation has become so efficient, in fact, that it has outstripped the ability of researchers to process resulting data. Dr Arun Konagurthu has taken up the challenge to provide better tools for data analysis.
Arun says the technologies to sequence DNA and determine protein structure are driving a wide range of advances in medicine, agriculture and other life sciences. Whole-genome sequencing, mass spectrometry and X-ray crystallography are just a few of the new techniques researchers are using to better understand the processes of life.
The result is an unprecedented deluge of digital information. Making sense of so much data requires a combination of problem solving, mathematics and computer science. Arun says understanding DNA sequencing data could be compared to taking many copies of a single newspaper edition, shredding them into billions pieces, and then trying to assemble a single copy of the paper from those pieces.
In particular, Arun is focusing on tools that will help to determine the three-dimensional structure of proteins. This is a prerequisite for understanding what different proteins do. “Proteins are the molecules of life,” he says. “My collaborators and I design and develop methods and algorithms that help structural biologists, life scientists and crystallographers gain insights into the structure of proteins, their architecture and function.”
In humans, for example, the family of proteins called ‘Serine Proteinases’ control many bodily processes including blood clotting and immune system responses. They are believed to play a significant role in conditions such as emphysema and arthritis.
“The function of these proteins can be explained by investigating their three-dimensional structures. Knowing what causes such diseased states helps to find a cure to them and computing plays an important role in these studies,” he says.
Arun’s research collaborators include Professor Arthur Lesk at the Hucks Institute for Genomics, Proteomics and Bioinformatics at Pennsylvania State University in the US, who is a pioneer in the field of protein science. Arun was able to work with Professor Lesk as a postdoctoral scholar in the US.
Ongoing collaboration has resulted in the development of a multiple structural alignment algorithm, called MUSTANG, for comparing the structures of proteins. This is available free, as an open-source program, through the internet. Professor James Whisstock at Monash University and Professor Peter Stuckey from the University of Melbourne were also part of the MUSTANG team and continue to collaborate with Arun on his research.
Arun grew up in an academic environment. His father was a university professor of genetics. He says he is indebted to the stimulating atmosphere his family created. It infused him with the focus and perseverance he needed to succeed in his chosen area of research. “There is a whole cornucopia of unsolved and fascinating problems in biology, discrete and continuous. These can be interrogated using computer science and mathematics. There are so many open, difficult problems that I am attracted to solving.”
applied algorithms, bioinformatics, bioinformatics, applied algorithms, computational biology and informatics
Mahmood, K., Webb, G.I., Song, J., Whisstock, J.C., Konagurthu, A.S., 2012, Efficient large-scale protein sequence comparison and gene matching to identify orthologs and co-orthologs, Nucleic Acids Research [P], vol 40, issue 6 (Art. ID: e44), Oxford University Press, UK, pp. 1-11.
Konagurthu, A.S., Lesk, A.M., Allison, L., 2012, Minimum message length inference of secondary structure from protein coordinate data, Bioinformatics [P], vol 28, issue 12, Oxford University Press, Oxford England, pp. i97-i105.
Collier, J., Lesk, A.M., Garcia De La Banda, M.J., Konagurthu, A.S., 2012, Super: A web server to rapidly screen superposable oligopeptide fragments from the protein data bank, Nucleic Acids Research [P], vol 40, Oxford University Press, Oxford England, pp. 1-6.
Konagurthu, A., Allison, L., Stuckey, P., Lesk, A., 2011, Piecewise linear approximation of protein structures using the principle of minimum message length, Bioinformatics [P], vol 27, issue 13, Oxford University Press, Oxford England, pp. i43-i51.
Zhang, L., Bailey, J., Konagurthu, A.S., Ramamohanarao, K., 2010, A fast indexing approach for protein structure comparison, BMC Bioinformatics [P], vol 11, issue S1, Biomed Central, London UK, pp. 1-9.
Konagurthu, A.S., Lesk, A.M., 2010, Cataloging topologies of protein folding patterns, Journal Of Molecular Recognition [P], vol 23, issue 2, John Wiley & Sons, Chichester UK, pp. 253-257.
Mahmood, K., Konagurthu, A.S., Song, J., Buckle, A.M., Webb, G.I., Whisstock, J.C., 2010, EGM: Encapsulated gene-by-gene matching to identify gene orthologs and homologous segments in genomes, Bioinformatics [P], vol 26, issue 17, Oxford University Press, UK, USA, pp. 2076-2084.
Konagurthu, A.S., Reboul, C.F., Schmidberger, J.W., Irving, J.A., Lesk, A.M., Stuckey, P.J., Whisstock, J.C., Buckle, A.M., 2010, MUSTANG-MR structural sieving server: Applications in protein structural analysis and crystallography, PLoS ONE [P], vol 5, issue 4 (e10048), Public Library of Science, USA, pp. 1-7.
Konagurthu, A.S., Lesk, A.M., 2008, On the origin of distribution patterns of motifs in biological networks, BMC Systems Biology [P], vol 2, Biomed Central, London UK, pp. 1-8.
Konagurthu, A.S., Lesk, A.M., 2008, Single and multiple input modules in regulatory networks, Proteins: Structure, Function, and Bioinformatics [P], vol 73, issue 2, Wiley-Liss, Hoboken NJ USA, pp. 320-324.
Konagurthu, A.S., Stuckey, P.J., Lesk, A., 2008, Structural search and retrieval using a tableau representation of protein folding patterns, Bioinformatics [P], vol 24, issue 5, Oxford University Press, Oxford UK, pp. 645-651.
Konagurthu, A.S., Whisstock, J.C., Stuckey, P.J., Lesk, A.M., 2006, MUSTANG: a multiple structural alignment algorithm, PROTEINS: Structure, Function, and Bioinformatics, vol 64, issue 3, Wiley-Liss, Div John Wiley & Sons Inc, Hoboken USA, pp. 559-574.
Konagurthu, A.S., Stuckey, P.J., 2006, Optimal sum-of-pairs multiple sequence alignment using incremental Carrillo and Lipman bounds, Journal of Computational Biology, vol 13, issue 3, Mary Ann Liebert Inc, New York USA, pp. 668-685.
Konagurthu, A., Whisstock, J., Stuckey, P., 2004, Progressive multiple alignment using sequence triplet optimizations and three-residue exchange costs, Journal of Bioinformatics and Computational Biology [P], vol 2, issue 4, Imperial College Press, London England, pp. 719-745.
Konagurthu, A.S., Allison, L., Conway, T., Beresford-Smith, B., Zobel, J., 2010, Design of an efficient out-of-core read alignment algorithm, Proceedings of the 10th International Workshop on Algorithms in Bioinformatics, 6 September 2010 to 8 September 2010, Springer-Verlag, Berlin Germany, pp. 189-201.
Dr Arun Konagurthu is the Chief Examiner for the following unit/s in the Faculty of IT;
Arun teaches the following units in the Faculty of IT;
Visiting professorships, fellowships, or other appointments
From: 01/01/2011 To: 31/12/2013
Faculty of Information Technology, Monash University
Larkins Fellow
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