Noam Shental (CS, The Open University of Israel)
Wednesday, 17.11.2010, 13:30
Identification of rare variants by resequencing is important both for detecting
novel variations and for screening individuals for known disease alleles. New
technologies enable low-cost resequencing of target regions, although it is
still prohibitive to test more than a few individuals. We propose a novel
pooling design that enables the recovery of novel or known rare alleles and
their carriers in groups of individuals. The method is based on a Compressed
Sensing (CS) approach, which is general, simple and efficient. CS allows the
use of generic algorithmic tools for simultaneous identification of multiple
variants and their carriers. We model the experimental procedure and show via
computer simulations that it enables the recovery of rare alleles and their
carriers in larger groups than were possible before. Our approach can also be
combined with barcoding techniques to provide a feasible solution based on
current resequencing costs. For example, when targeting a small enough genomic
region (~100 bp) and using only ~10 sequencing lanes and ~10 distinct barcodes
per lane, one recovers the identity of 4 rare allele carriers out of a
population of over 4000 individuals. We demonstrate the performance of our
approach over several publicly available experimental data sets, including the
1000 Genomes Pilot 3 study.
We believe our approach may significantly improve cost effectiveness in future
Genome Wide Association Studies, and in screening large DNA cohorts for
specific risk alleles.
Joint work with Amnon Amir from the Weizmann Institute of Science, and Or Zuk
from the Broad Institute of MIT and Harvard.
Host: Tomer Shlomi .