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Frequency-based haplotype reconstruction from deep sequencing data of bacterial populations

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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.
Keywords
ASEXUAL POPULATIONS, COVERAGE, GENETIC-VARIATION, EVOLUTION, QUASI-SPECIES RECONSTRUCTION, IBCN, CELL

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MLA
Pulido Tamayo, Sergio, et al. “Frequency-Based Haplotype Reconstruction from Deep Sequencing Data of Bacterial Populations.” NUCLEIC ACIDS RESEARCH, vol. 43, no. 16, 2015, doi:10.1093/nar/gkv478.
APA
Pulido Tamayo, S., Sanchez Rodriguez, A., Swings, T., Van den Berghe, B., Dubey, A., Steenackers, H., … Marchal, K. (2015). Frequency-based haplotype reconstruction from deep sequencing data of bacterial populations. NUCLEIC ACIDS RESEARCH, 43(16). https://doi.org/10.1093/nar/gkv478
Chicago author-date
Pulido Tamayo, Sergio, Aminael Sanchez Rodriguez, Toon Swings, Bram Van den Berghe, Akanksha Dubey, Hans Steenackers, Jan Michiels, Jan Fostier, and Kathleen Marchal. 2015. “Frequency-Based Haplotype Reconstruction from Deep Sequencing Data of Bacterial Populations.” NUCLEIC ACIDS RESEARCH 43 (16). https://doi.org/10.1093/nar/gkv478.
Chicago author-date (all authors)
Pulido Tamayo, Sergio, Aminael Sanchez Rodriguez, Toon Swings, Bram Van den Berghe, Akanksha Dubey, Hans Steenackers, Jan Michiels, Jan Fostier, and Kathleen Marchal. 2015. “Frequency-Based Haplotype Reconstruction from Deep Sequencing Data of Bacterial Populations.” NUCLEIC ACIDS RESEARCH 43 (16). doi:10.1093/nar/gkv478.
Vancouver
1.
Pulido Tamayo S, Sanchez Rodriguez A, Swings T, Van den Berghe B, Dubey A, Steenackers H, et al. Frequency-based haplotype reconstruction from deep sequencing data of bacterial populations. NUCLEIC ACIDS RESEARCH. 2015;43(16).
IEEE
[1]
S. Pulido Tamayo et al., “Frequency-based haplotype reconstruction from deep sequencing data of bacterial populations,” NUCLEIC ACIDS RESEARCH, vol. 43, no. 16, 2015.
@article{6990457,
  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.}},
  articleno    = {{e105}},
  author       = {{Pulido Tamayo, Sergio and Sanchez Rodriguez, Aminael and Swings, Toon and Van den Berghe, Bram and Dubey, Akanksha and Steenackers, Hans and Michiels, Jan and Fostier, Jan and Marchal, Kathleen}},
  issn         = {{0305-1048}},
  journal      = {{NUCLEIC ACIDS RESEARCH}},
  keywords     = {{ASEXUAL POPULATIONS,COVERAGE,GENETIC-VARIATION,EVOLUTION,QUASI-SPECIES RECONSTRUCTION,IBCN,CELL}},
  language     = {{eng}},
  number       = {{16}},
  pages        = {{13}},
  title        = {{Frequency-based haplotype reconstruction from deep sequencing data of bacterial populations}},
  url          = {{http://doi.org/10.1093/nar/gkv478}},
  volume       = {{43}},
  year         = {{2015}},
}

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