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More accurate protein sequence alignments for molecular genetics

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03.11.2008

Sequence alignments are the basic tools of genomics research. In her doctoral thesis, Bioinformatics Scientist Virpi Ahola of MTT introduces a method for assessing the quality of protein sequence alignments.

In recent years, the whole genome sequencing projects of the human species and several other species have produced large amounts of raw sequence data. This consists of the establishment of DNA sequence of four bases (A, C, G and T). A genome contains DNA, which in turn contains the genetic information of an organism – in other words, instructions as to what the organism is like.

Virpi Ahola studied the protein sequence alignments of various species. The aim is to align the sequences of different species on top of each other so that the evolutionally, structurally or functionally corresponding positions of sequences appear in the same column. The length of the alignments varies from 50 or so to thousands of amino acids.

BASIC RESEARCH FOR MANY DIFFERENT DISCIPLINES

Nowadays, the alignments are performed with computer software. Virpi Ahola explains that this constitutes basic research that can be used in nearly all of the applications of molecular genomics, e.g. in medical and pharmaceutical research, plant and animal breeding, in food research and the conservation of animal and plant genetic resources.

“It is important to strive for maximal accuracy in the alignments, in order to prevent mistakes in the analysis in its early stages,” stresses Ahola.

The statistical method that she has developed predicts the likelihood of matching the same positions of proteins from different species. “Even though arranging sequences of letters on top of each other may seem easy, performing the alignments is actually a highly demanding task. No comprehensive mathematical or computational solution has so far been found for the problem of aligning multiple sequences,” comments Ahola.

MANY NEW IDEAS FOR METHODOLOGY

The biological relevance of the method developed by Virpi Ahola is verified by quality control. This is achieved with the help of databases providing biologically plausible alignments. In her study, Ahola realigned these sequences. The new alignments were then compared to the alignments provided by the database with the method described in the thesis. The result of the calculation was then tested by comparing it to the “true” quality of the alignment.

“The results show that my method can be used to reliably predict the quality of alignments,” Virpi Ahola concludes.

In her doctoral thesis, Ahola introduces a method that can be used to locate functionally and structurally important sites of proteins.

The doctoral thesis in Statistics “Statistical methods for conservation and alignment quality in proteins” by Virpi Ahola (MSocSc) will be cross-examined at the University of Turku on 7 November 2008. The opponent is Professor Arne Elofsson from Sweden and the custodian Professor Esa Uusipaikka.

For more information, please contact: Virpi Ahola, MTT Agrifood Research Finland, virpi.ahola@mtt.fi , +358 (0)3 4188 3202

Ulla Jauhiainen | Source: alphagalileo
Further information: www.mtt.fi
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