Pooled genomic indexing (PGI): Mathematical analysis and experiment design

Abstract

Pooled Genomic Indexing (PGI) is a novel method for physical mapping of clones onto known macromolecular sequences. PGI is carried out by pooling arrayed clones, generating shotgun sequence reads from pools and by comparing the reads against a reference sequence. If two reads from two different pools match the reference sequence at a close distance, they are both assigned (deconvoluted) to the clone at the intersection of the two pools and the clone is mapped onto the region of the reference sequence between the two matches. A probabilistic model for PGI is developed, and several pooling schemes are designed and analyzed. The probabilistic model and the pooling schemes are validated in simulated experiments where 625 rat BAC clones and 207 mouse BAC clones are mapped onto homologous human sequence.