Group Testing With DNA Chips: Generating Designs and Decoding Experiments

  • Authors:
  • Alexander Schliep;David C. Torney;Sven Rahmann

  • Affiliations:
  • -;-;-

  • Venue:
  • CSB '03 Proceedings of the IEEE Computer Society Conference on Bioinformatics
  • Year:
  • 2003

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Abstract

DNA microarrays are a valuable tool for massivelyparallel DNA-DNA hybridization experiments. Currently,most applications rely on the existence of sequence-specificoligonucleotide probes. In large families of closely relatedtarget sequences, such as different virus subtypes, thehigh degree of similarity often makes it impossible to find aunique probe for every target. Fortunately, this is unnecessary.We propose a microarray design methodology based ona group testing approach. While probes might bind to multipletargets simultaneously, a properly chosen probe set canstill unambiguously distinguish the presence of one targetset from the presence of a different target set. Our methodis the first one that explicitly takes cross-hybridization andexperimental errors into account while accommodating severaltargets.The approach consists of three steps: (1) Pre-selection ofprobe candidates, (2) Generation of a suitable group testingdesign, and (3) Decoding of hybridization results to inferpresence or absence of individual targets.Our results show that this approach is very promising,even for challenging data sets and experimental error ratesof up to 5%. On a data set of 28S rDNA sequences wewere able to identify 660 sequences, a substantial improvementover a prior approach using unique probes which onlyidentified 408 sequences.