Multiplex Sequencing by Hybridization

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Abstract
One of the limitations of classical sequencing by hybridization (SBH) is the inefficient use of probes in the "all k-mers" array. This limitation occurs due to the relatively short length (roughly √C) of target that may be reconstructed by an array with C probes. We propose a new strategy, multiplex sequencing by hybridization, that greatly increases the efficiency of target reconstruction. In the typical multiplex SBH method, many different target sequences are simultaneously reconstructed (as compared to a single sequence in classic SBH). This is accomplished by pooling the target sequences and performing several hybridization experiments. This procedure makes more efficient use of probes so that the combined length of sequence reconstructed per DNA array increases significantly as compared to classical SBH.