One of the limitations of classical sequencing by hybridization (SBH) is th
e inefficient use of probes in the "all k-mers" array, This limitation occu
rs due to the relatively short length (roughly rootC) of target that may be
reconstructed by an array with C probes. We propose a new strategy, multip
lex sequencing by hybridization, that greatly increases the efficiency of t
arget reconstruction. In the typical multiplex SBH method, many different t
arget sequences are simultaneously reconstructed (as compared to a single s
equence in classic SBH). This is accomplished by pooling the target sequenc
es and performing several hybridization experiments, This procedure makes m
ore efficient use of probes so that the combined length of sequence reconst
ructed per DNA array increases significantly as compared to classical SBH.