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, including the detection of rare OTU's in a sample. In some cases, methods are provided for selecting an oligonucleotide probe specific for a node on a clustering tree.
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, and a grant from the National Institutes of Health having Award Number AI075410. The government has certain rights in this invention.