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Disseqt-distribution-based modeling of sequence space time dynamics

Henningsson, R. LU ; Moratorio, G. ; Bordería, A. V. ; Vignuzzi, M. and Fontes, M. LU (2019) In Virus Evolution 5(2).
Abstract

Rapidly evolving microbes are a challenge to model because of the volatile, complex, and dynamic nature of their populations. We developed the DISSEQT pipeline (DIStribution-based SEQuence space Time dynamics) for analyzing, visualizing, and predicting the evolution of heterogeneous biological populations in multidimensional genetic space, suited for population-based modeling of deep sequencing and high-throughput data. The pipeline is openly available on GitHub (https://github.com/rasmushenningsson/DISSEQT.jl, accessed 23 June 2019) and Synapse (https://www.synapse.org/#!Synapse: syn11425758, accessed 23 June 2019), covering the entire workflow from read alignment to visualization of results. Our pipeline is centered around robust... (More)

Rapidly evolving microbes are a challenge to model because of the volatile, complex, and dynamic nature of their populations. We developed the DISSEQT pipeline (DIStribution-based SEQuence space Time dynamics) for analyzing, visualizing, and predicting the evolution of heterogeneous biological populations in multidimensional genetic space, suited for population-based modeling of deep sequencing and high-throughput data. The pipeline is openly available on GitHub (https://github.com/rasmushenningsson/DISSEQT.jl, accessed 23 June 2019) and Synapse (https://www.synapse.org/#!Synapse: syn11425758, accessed 23 June 2019), covering the entire workflow from read alignment to visualization of results. Our pipeline is centered around robust dimension and model reduction algorithms for analysis of genotypic data with additional capabilities for including phenotypic features to explore dynamic genotype-phenotype maps. We illustrate its utility and capacity with examples from evolving RNA virus populations, which present one of the highest degrees of genetic heterogeneity within a given population found in nature. Using our pipeline, we empirically reconstruct the evolutionary trajectories of evolving populations in sequence space and genotype-phenotype fitness landscapes. We show that while sequence space is vastly multidimensional, the relevant genetic space of evolving microbial populations is of intrinsically low dimension. In addition, evolutionary trajectories of these populations can be faithfully monitored to identify the key minority genotypes contributing most to evolution. Finally, we show that empirical fitness landscapes, when reconstructed to include minority variants, can predict phenotype from genotype with high accuracy.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Applied mathematics, Multidimensional scaling, Ngs, Quasispecies
in
Virus Evolution
volume
5
issue
2
article number
vez028
publisher
Oxford University Press
external identifiers
  • scopus:85102576217
ISSN
2057-1577
DOI
10.1093/ve/vez028
language
English
LU publication?
yes
id
b1fc2c89-c473-4b31-827e-1001eb2a6001
date added to LUP
2021-03-30 08:40:15
date last changed
2022-04-19 05:33:18
@article{b1fc2c89-c473-4b31-827e-1001eb2a6001,
  abstract     = {{<p>Rapidly evolving microbes are a challenge to model because of the volatile, complex, and dynamic nature of their populations. We developed the DISSEQT pipeline (DIStribution-based SEQuence space Time dynamics) for analyzing, visualizing, and predicting the evolution of heterogeneous biological populations in multidimensional genetic space, suited for population-based modeling of deep sequencing and high-throughput data. The pipeline is openly available on GitHub (https://github.com/rasmushenningsson/DISSEQT.jl, accessed 23 June 2019) and Synapse (https://www.synapse.org/#!Synapse: syn11425758, accessed 23 June 2019), covering the entire workflow from read alignment to visualization of results. Our pipeline is centered around robust dimension and model reduction algorithms for analysis of genotypic data with additional capabilities for including phenotypic features to explore dynamic genotype-phenotype maps. We illustrate its utility and capacity with examples from evolving RNA virus populations, which present one of the highest degrees of genetic heterogeneity within a given population found in nature. Using our pipeline, we empirically reconstruct the evolutionary trajectories of evolving populations in sequence space and genotype-phenotype fitness landscapes. We show that while sequence space is vastly multidimensional, the relevant genetic space of evolving microbial populations is of intrinsically low dimension. In addition, evolutionary trajectories of these populations can be faithfully monitored to identify the key minority genotypes contributing most to evolution. Finally, we show that empirical fitness landscapes, when reconstructed to include minority variants, can predict phenotype from genotype with high accuracy. </p>}},
  author       = {{Henningsson, R. and Moratorio, G. and Bordería, A. V. and Vignuzzi, M. and Fontes, M.}},
  issn         = {{2057-1577}},
  keywords     = {{Applied mathematics; Multidimensional scaling; Ngs; Quasispecies}},
  language     = {{eng}},
  number       = {{2}},
  publisher    = {{Oxford University Press}},
  series       = {{Virus Evolution}},
  title        = {{Disseqt-distribution-based modeling of sequence space time dynamics}},
  url          = {{http://dx.doi.org/10.1093/ve/vez028}},
  doi          = {{10.1093/ve/vez028}},
  volume       = {{5}},
  year         = {{2019}},
}