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 microrganisms 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.
STATEMENT AS TO FEDERALLY SPONSORED RESEARCH
 This invention was made with Government support under Contract No. DE-AC02-05CH11231 awarded by the Department of Energy; a grant from the Department of Homeland Security and Agreement Number 07-576-550-0 from State of California Water Quality Board. The government has certain rights in this invention.