Biotechnology

Overview

Our research in this area focuses on two themes:

Biotech Supply. Laboratory instruments for life sciences typically need sophisticated software components, e.g. for scheduling robot arm movements, dispensation orders, assay design, or data analysis. The design of such components requires combinatorial problem solving, and is an excellent application area for the constraint technology supplied by the CPS group.

Bioinformatics and Functional Genomics. We conduct projects addressing specific biological problems, in collaboration with biologists. SICS's responsibility in these projects is typically to provide expertise in the computer science and bioinformatics aspects.

Projects

• DispGen (2003) - a project to develop a dispensation order generator for Pyrosequencing's sequence analysis instruments, using constraint programming technology. The generator computes an instruction sequence based on an input specification. Funding provided by Pyrosequencing AB, an Uppsala company offering complete solutions for applications including genetics, drug discovery, microbiology, SNP and mutation analysis, forensic identification, pharmacogenomics, and bacterial and viral typing.

• GENKOMB (2003) - The aim of the GENKOMB project was to find and analyse transcription factor binding sites in the human genome, by correlating expression data for a set of genes with the nucleotide sequences in their upstream regions. Apart from detecting transcription factor binding sites, this project has resulted in programs for matching weight matrices to DNA sequences and multiple alignment of short nucleotide sequences. In collaboration with AstraZeneca AB.

  Main funding provided by VINNOVA.

• GENFUNK (2001-2002) - This project, carried out in collaboration with Global Genomics AB, studied a novel approach of measuring the global gene expression in a tissue sample. In the method, mRNA is extracted from the sample and transformed into cDNA captured on magnetic beads. This is then acted on by type IIS restriction endonucleases, which recognize certain short DNA sequences and cut the DNA close to those sequences. The resulting fragments are amplified in PCR with selected ligation fragments, and displayed in capillary electrophoresis. Determining the gene expression levels from the peak data is combinatorial optimization problem, which can in principle be solved, to give expression levels of most genes active in sampled cells, with good accuracy.

  Main funding provided by VINNOVA.

Researchers

• Mats Carlsson, Ph.D. (principal investigator)

Publications

• Mats Carlsson. Dispensation order generation for pyrosequencing. ERCIM News, (60), 2005.

• Adam Ameur, Erik Aurell, Mats Carlsson, and Jakub Orzechowski Westholm. Global gene expression analysis by combinatorial optimization. In Silico Biology, 4(0020), 2004.

• Mats Carlsson and Nicolas Beldiceanu. Dispensation order generation for pyrosequencing. In Yi-Ping Phoebe Chen, editor, Proc. APBC2004, volume 29 of Conferences in Research and Practice in Information technology, Dunedin, New Zealand, 2004. Australian Computer Society.

• Mats Carlsson and Nicolas Beldiceanu. Multiplex dispensation order generation for pyrosequencing. In CP'2004 Workshop on CSP Techniques with Immediate Application, 2004.

• Jakub Orzechowski Westholm and Adam Ameur. GENKOMB Project Report. SICS Technical Report T2003-14, Swedish Institute of Computer Science, 2003.

• Erik Aurell, Mats Carlsson, Jan Ekman, and Per Kreuger. GENFUNK. SICS Technical Report T2002-15, Swedish Institute of Computer Science, 2002.

• Jakub Orzechowski Westholm and Adam Ameur. Local search methods in gene expression analysis. SICS Technical Report T2002-12, Swedish Institute of Computer Science, 2002.