title: Predicting Carriers of Ongoing Selective Sweeps without Knowledge of the Favored Allele.
abstract: Methods for detecting the genomic signatures of natural selection have been heavily studied, and they have been successful in identifying many selective sweeps. For most of these sweeps, the favored allele remains unknown, making it difficult to distinguish carriers of the sweep from non-carriers. In an ongoing selective sweep, carriers of the favored allele are likely to contain a future most recent common ancestor. Therefore, identifying them may prove useful in predicting the evolutionary trajectory--for example, in contexts involving drug-resistant pathogen strains or cancer subclones. The main contribution of this paper is the development and analysis of a new statistic, the Haplotype Allele Frequency (HAF) score. The HAF score, assigned to individual haplotypes in a sample, naturally captures many of the properties shared by haplotypes carrying a favored allele. We provide a theoretical framework for computing expected HAF scores under different evolutionary scenarios, and we validate the theoretical predictions with simulations. As an application of HAF score computations, we develop an algorithm (PreCIOSS: Predicting Carriers of Ongoing Selective Sweeps) to identify carriers of the favored allele in selective sweeps, and we demonstrate its power on simulations of both hard and soft sweeps, as well as on data from well-known sweeps in human populations.
authors.affiliation: Bioinformatics Graduate Program, University of California, San Diego, La Jolla, California, United States of America.
authors.forename: Roy
authors.initials: R
authors.lastname: Ronen
authors.affiliation: Department of Mathematics, University of California, San Diego, La Jolla, California, United States of America.
authors.forename: Glenn
authors.initials: G
authors.lastname: Tesler
authors.affiliation: Department of Electrical & Computer Engineering, University of California, San Diego, La Jolla, California, United States of America.
authors.forename: Ali
authors.initials: A
authors.lastname: Akbari
authors.affiliation: Department of Computer Science & Engineering, University of California, San Diego, La Jolla, California, United States of America.
authors.forename: Shay
authors.initials: S
authors.lastname: Zakov
authors.affiliation: Department of Biology, Stanford University, Stanford, California, United States of America.
authors.forename: Noah A
authors.initials: NA
authors.lastname: Rosenberg
authors.affiliation: Department of Computer Science & Engineering, University of California, San Diego, La Jolla, California, United States of America.
authors.forename: Vineet
authors.initials: V
authors.lastname: Bafna
mesh_terms: D000465:Algorithms; D000483:Alleles; D006580:Genetic Carrier Screening; D006239:Haplotypes; D006801:Humans; D008962:Models, Theoretical; D012641:Selection, Genetic