title: Frequency-based haplotype reconstruction from deep sequencing data of bacterial populations.
abstract: Clonal populations accumulate mutations over time, resulting in different haplotypes. Deep sequencing of such a population in principle provides information to reconstruct these haplotypes and the frequency at which the haplotypes occur. However, this reconstruction is technically not trivial, especially not in clonal systems with a relatively low mutation frequency. The low number of segregating sites in those systems adds ambiguity to the haplotype phasing and thus obviates the reconstruction of genome-wide haplotypes based on sequence overlap information.Therefore, we present EVORhA, a haplotype reconstruction method that complements phasing information in the non-empty read overlap with the frequency estimations of inferred local haplotypes. As was shown with simulated data, as soon as read lengths and/or mutation rates become restrictive for state-of-the-art methods, the use of this additional frequency information allows EVORhA to still reliably reconstruct genome-wide haplotypes. On real data, we show the applicability of the method in reconstructing the population composition of evolved bacterial populations and in decomposing mixed bacterial infections from clinical samples.
authors.affiliation: Department of Information Technology, Ghent University, iMinds, 9050 Gent, Belgium Department of Microbial and Molecular Systems, Centre of Microbial and Plant Genetics, KU Leuven, Kasteelpark Arenberg 20, 3001 Leuven, Belgium Department of Plant Biotechnology and Bioinformatics, Ghent University, 9052 Ghent, Belgium.
authors.forename: Sergio
authors.initials: S
authors.lastname: Pulido-Tamayo
authors.affiliation: Department of Microbial and Molecular Systems, Centre of Microbial and Plant Genetics, KU Leuven, Kasteelpark Arenberg 20, 3001 Leuven, Belgium Departamento de Ciencias Naturales, Universidad Técnica Particular de Loja, San Cayetano Alto S/N, EC1101608 Loja, Ecuador.
authors.forename: Aminael
authors.initials: A
authors.lastname: Sánchez-Rodríguez
authors.affiliation: Department of Microbial and Molecular Systems, Centre of Microbial and Plant Genetics, KU Leuven, Kasteelpark Arenberg 20, 3001 Leuven, Belgium.
authors.forename: Toon
authors.initials: T
authors.lastname: Swings
authors.affiliation: Department of Microbial and Molecular Systems, Centre of Microbial and Plant Genetics, KU Leuven, Kasteelpark Arenberg 20, 3001 Leuven, Belgium.
authors.forename: Bram
authors.initials: B
authors.lastname: Van den Bergh
authors.affiliation: Department of Microbial and Molecular Systems, Centre of Microbial and Plant Genetics, KU Leuven, Kasteelpark Arenberg 20, 3001 Leuven, Belgium.
authors.forename: Akanksha
authors.initials: A
authors.lastname: Dubey
authors.affiliation: Department of Microbial and Molecular Systems, Centre of Microbial and Plant Genetics, KU Leuven, Kasteelpark Arenberg 20, 3001 Leuven, Belgium.
authors.forename: Hans
authors.initials: H
authors.lastname: Steenackers
authors.affiliation: Department of Microbial and Molecular Systems, Centre of Microbial and Plant Genetics, KU Leuven, Kasteelpark Arenberg 20, 3001 Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Michiels
authors.affiliation: Department of Information Technology, Ghent University, iMinds, 9050 Gent, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Fostier
authors.affiliation: Department of Information Technology, Ghent University, iMinds, 9050 Gent, Belgium Department of Microbial and Molecular Systems, Centre of Microbial and Plant Genetics, KU Leuven, Kasteelpark Arenberg 20, 3001 Leuven, Belgium Department of Plant Biotechnology and Bioinformatics, Ghent University, 9052 Ghent, Belgium kathleen.marchal@ugent.be.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Marchal
mesh_terms: D001424:Bacterial Infections / Q000382:microbiology; D060085:Coinfection / Q000382:microbiology; D004926:Escherichia coli / Q000235:genetics; D019143:Evolution, Molecular; D016680:Genome, Bacterial; D006239:Haplotypes; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA / Q000379:methods*