  Detection of rare variants by resequencing is important for the
identification of individuals carrying disease variants. Rapid sequencing by
new technologies enables low-cost resequencing of target regions, although it
is still prohibitive to test more than a few individuals. In order to improve
cost trade-offs, it has recently been suggested to apply pooling designs which
enable the detection of carriers of rare alleles in groups of individuals.
However, this was shown to hold only for a relatively low number of individuals
in a pool, and requires the design of pooling schemes for particular cases.
  We propose a novel pooling design, based on a compressed sensing approach,
which is both general, simple and efficient. We model the experimental
procedure and show via computer simulations that it enables the recovery of
rare allele carriers out of larger groups than were possible before, especially
in situations where high coverage is obtained for each individual.
  Our approach can also be combined with barcoding techniques to enhance
performance and provide a feasible solution based on current resequencing
costs. For example, when targeting a small enough genomic region (~100
base-pairs) and using only ~10 sequencing lanes and ~10 distinct barcodes, one
can recover the identity of 4 rare allele carriers out of a population of over
4000 individuals.
