A method and system for generating system

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The present invention discloses methods and systems for designing and using organism-specific and/or operational taxon unit (OTU)-specific probes. The methods and systems allow for detecting, identifying and quantitating a plurality of biomolecules or microorganisms in a sample based on the hybridization or binding of target molecules in the sample with the probes. Some embodiments provide methods of selecting an oligonucleotide probe specific for a node on a clustering tree. Other embodiments provide methods of selecting organism-specific or OTU-specific oligonucleotide probes for use in accurately detecting a plurality of organisms in a sample with high confidence. Some embodiments provide methods and systems to detect the presence of a rare OTU in a sample.