Viral Quasispecies Assembly via Maximal Clique Enumeration
Publication Date
March 27, 2014
Journal
PLOS Computational Biology
Authors
Armin Töpfer, Tobias Marschall, Rowena A. Bull, Fabio Luciani, et al
Volume
10
Issue
3
Pages
e1003515
DOI
https://dx.plos.org/10.1371/journal.pcbi.1003515
Publisher URL
http://journals.plos.org/ploscompbiol/article?id=10.1371%2Fjournal.pcbi.1003515
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/24675810
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967922
Europe PMC
http://europepmc.org/abstract/MED/24675810
Web of Science
000336509000032
Scopus
84897392958
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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1438170"], "description"=>"<p>Estimated deletion size deviation and false negative rate for different true deletion sizes of (A) 100, (B) 500, and (C) 1000 bp. For each deletion length and each coverage of 5, 12, 24, 48, 96, and 144×, a boxplot summarizes the deviations of the estimated to the true deletion size in 100 simulated samples. The blue line represents the number of false negative predicted deletions in each of the 100 samples.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome analysis tools", "Sequence assembly tools", "Genome sequencing", "Structural genomics", "population genetics", "haplotypes", "microbiology", "Virology", "deletion"], "article_id"=>976781, "categories"=>["Biological Sciences"], "users"=>["Armin Töpfer", "Tobias Marschall", "Rowena A. Bull", "Fabio Luciani", "Alexander Schönhuth", "Niko Beerenwinkel"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003515.g003", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Large_deletion_estimates_/976781", "title"=>"Large deletion estimates.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-27 03:19:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1438169"], "description"=>"<p>(A) Ten haplotypes were sampled with different frequencies (x-axis, logarithmic scale), and the mean deviations of the estimated to the true frequencies are reported for ten repetitions of the simulation (y-axis). The different symbols represent data sets with coverages 400×, 800×, and 1600×. Color indicates whether the genome was fully covered by predicted haplotypes (blue) or not (orange). (B) Performance in distinguishing reconstructed local haplotypes, depending on pairwise distance and coverage. The displayed percentages are the fractions of super-reads that do not match any true haplotype without error. Color-coded is the fraction of super-reads that match exactly one true haplotype (100%, orange; , blue; , violet).</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome analysis tools", "Sequence assembly tools", "Genome sequencing", "Structural genomics", "population genetics", "haplotypes", "microbiology", "Virology", "estimation", "distinguishing", "reconstructed"], "article_id"=>976780, "categories"=>["Biological Sciences"], "users"=>["Armin Töpfer", "Tobias Marschall", "Rowena A. Bull", "Fabio Luciani", "Alexander Schönhuth", "Niko Beerenwinkel"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003515.g002", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Performance_in_A_frequency_estimation_and_B_distinguishing_reconstructed_local_haplotypes_/976780", "title"=>"Performance in (A) frequency estimation and (B) distinguishing reconstructed local haplotypes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-27 03:19:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1438174", "https://ndownloader.figshare.com/files/1438175", "https://ndownloader.figshare.com/files/1438176", "https://ndownloader.figshare.com/files/1438177", "https://ndownloader.figshare.com/files/1438178", "https://ndownloader.figshare.com/files/1438179"], "description"=>"<div><p>Virus populations can display high genetic diversity within individual hosts. The intra-host collection of viral haplotypes, called viral quasispecies, is an important determinant of virulence, pathogenesis, and treatment outcome. We present HaploClique, a computational approach to reconstruct the structure of a viral quasispecies from next-generation sequencing data as obtained from bulk sequencing of mixed virus samples. We develop a statistical model for paired-end reads accounting for mutations, insertions, and deletions. Using an iterative maximal clique enumeration approach, read pairs are assembled into haplotypes of increasing length, eventually enabling global haplotype assembly. The performance of our quasispecies assembly method is assessed on simulated data for varying population characteristics and sequencing technology parameters. Owing to its paired-end handling, HaploClique compares favorably to state-of-the-art haplotype inference methods. It can reconstruct error-free full-length haplotypes from low coverage samples and detect large insertions and deletions at low frequencies. We applied HaploClique to sequencing data derived from a clinical hepatitis C virus population of an infected patient and discovered a novel deletion of length 357±167 bp that was validated by two independent long-read sequencing experiments. HaploClique is available at <a href=\"https://github.com/armintoepfer/haploclique\" target=\"_blank\">https://github.com/armintoepfer/haploclique</a>. A summary of this paper appears in the proceedings of the RECOMB 2014 conference, April 2-5.</p></div>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome analysis tools", "Sequence assembly tools", "Genome sequencing", "Structural genomics", "population genetics", "haplotypes", "microbiology", "Virology", "quasispecies", "maximal", "clique"], "article_id"=>976785, "categories"=>["Biological Sciences"], "users"=>["Armin Töpfer", "Tobias Marschall", "Rowena A. Bull", "Fabio Luciani", "Alexander Schönhuth", "Niko Beerenwinkel"], "doi"=>["https://dx.doi.org/10.1371/journal.pcbi.1003515.s001", "https://dx.doi.org/10.1371/journal.pcbi.1003515.s002", "https://dx.doi.org/10.1371/journal.pcbi.1003515.s003", "https://dx.doi.org/10.1371/journal.pcbi.1003515.s004", "https://dx.doi.org/10.1371/journal.pcbi.1003515.s005", "https://dx.doi.org/10.1371/journal.pcbi.1003515.s006"], "stats"=>{"downloads"=>18, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Viral_Quasispecies_Assembly_via_Maximal_Clique_Enumeration_/976785", "title"=>"Viral Quasispecies Assembly via Maximal Clique Enumeration", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-03-27 03:19:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1438172"], "description"=>"<p>Minimum, maximum, and mean read lengths (A) and the total number of reads (B) for the global haplotype assembly of the lab-mix, for the first 13 and the last iteration (30).</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome analysis tools", "Sequence assembly tools", "Genome sequencing", "Structural genomics", "population genetics", "haplotypes", "microbiology", "Virology", "haplotype"], "article_id"=>976783, "categories"=>["Biological Sciences"], "users"=>["Armin Töpfer", "Tobias Marschall", "Rowena A. Bull", "Fabio Luciani", "Alexander Schönhuth", "Niko Beerenwinkel"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003515.g004", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Global_haplotype_assembly_results_/976783", "title"=>"Global haplotype assembly results.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-27 03:19:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1438173"], "description"=>"<p>Global haplotype assembly comparison of HaploClique with the software packages ShoRAH <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003515#pcbi.1003515-Zagordi3\" target=\"_blank\">[33]</a>, PredictHaplo <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003515#pcbi.1003515-Prabhakaran1\" target=\"_blank\">[14]</a>, and QuRe <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003515#pcbi.1003515-Prosperi1\" target=\"_blank\">[16]</a>. We report the estimated variant frequencies and, in parenthesis, the maximal length of the reconstructed haplotypes relative to the genome length, for each of the five variants. In the remaining columns, the average error rate (computed as the number of mistaken nucleotides, divided by the length of the haplotype computed), the total number of reconstructed haplotypes, and the precision (percentage of perfectly reconstructed haplotypes weighted by the respective estimated frequency) are reported. See <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003515#s5\" target=\"_blank\">Methods</a> for more details on frequency estimation.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome analysis tools", "Sequence assembly tools", "Genome sequencing", "Structural genomics", "population genetics", "haplotypes", "microbiology", "Virology", "haplotype"], "article_id"=>976784, "categories"=>["Biological Sciences"], "users"=>["Armin Töpfer", "Tobias Marschall", "Rowena A. Bull", "Fabio Luciani", "Alexander Schönhuth", "Niko Beerenwinkel"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003515.t001", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Global_haplotype_assembly_comparison_/976784", "title"=>"Global haplotype assembly comparison.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-03-27 03:19:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1438167"], "description"=>"<p>(A) Example of a read alignment graph based on the insert size criterion. Alignments of read pairs are shown in gray and the corresponding nodes in the graph representation are depicted in blue. The four bottom-most alignment pairs stem from a haplotype harboring a deletion (shown in orange in the reference genome) and therefore display a larger insert size than the remaining alignment pairs. Note that the four deletion-indicating alignment pairs form a max-clique (circled in orange). (B) Illustration of the compatible gaps condition of the sequence similarity criterion. Two reads and are aligned against the reference (left). This induces a direct read-to-read alignment of and (right). Case (1): No gaps in the reference alignments lead to a gapless read-to-read alignment, which renders the pair of reads an edge candidate. Case (2): Gaps in the reference alignment lead to gaps in the read-to-read alignment, excluding the possibility of an edge. See also <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003515#pcbi.1003515.s006\" target=\"_blank\">Figure S6</a> in the appendix for more complicated cases involving gaps.</p>", "links"=>[], "tags"=>["Computational biology", "genomics", "Genome analysis tools", "Sequence assembly tools", "Genome sequencing", "Structural genomics", "population genetics", "haplotypes", "microbiology", "Virology", "enumeration"], "article_id"=>976778, "categories"=>["Biological Sciences"], "users"=>["Armin Töpfer", "Tobias Marschall", "Rowena A. Bull", "Fabio Luciani", "Alexander Schönhuth", "Niko Beerenwinkel"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003515.g001", "stats"=>{"downloads"=>0, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Max_clique_enumeration_and_edge_definitions_/976778", "title"=>"Max-clique enumeration and edge definitions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-27 03:19:26"}

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