1 / 17

DNA Assembly with Gaps: Simulating Sequence Evolution

DNA Assembly with Gaps: Simulating Sequence Evolution. Reed A. Cartwright Department of Genetics University of Georgia. Synopsis. Explain the importance of simulations. Introduce Dawg, a new sequence simulation program. Example usage of Dawg. Why Simulate Phylogenies?.

yama
Télécharger la présentation

DNA Assembly with Gaps: Simulating Sequence Evolution

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. DNA Assembly with Gaps: Simulating Sequence Evolution Reed A. Cartwright Department of Genetics University of Georgia

  2. Synopsis • Explain the importance of simulations. • Introduce Dawg, a new sequence simulation program. • Example usage of Dawg. RA Cartwright rac@uga.edu - http://scit.us/

  3. Why Simulate Phylogenies? • Biologists use many techniques to reconstruct phylogenies based on biological data. • However, true phylogenies are unknown, except for a few instances. • How then can we test the accuracy of these reconstruction methods? • Use simulations. RA Cartwright rac@uga.edu - http://scit.us/

  4. Why Simulate Phylogenies? • Techniques are often based on certain models of evolution. • Simulating sequence evolution based on these models produces an ideal situation to test the techniques. • Using other models can test how robust a technique is. RA Cartwright rac@uga.edu - http://scit.us/

  5. A A B B C C D D A B C D Testing Procedure 1. Start with a “known” tree. 3. Estimate the trees of the simulated data. 2. Simulate sequence sets based on the tree. 4. Compare estimated trees to the original tree. A AATTCTTTGAGTTAA B AATTCTTTGAGTTAA C AATTCTTAAAGTTAA D AATTCTTAAAGTTAA A AAAAGATAAAGCAAA--A B GAAAGATAAAGCAAA--A C GAAAGATAAAGAAAAACA D GAAAGATAAAGAAAAACA RA Cartwright rac@uga.edu - http://scit.us/

  6. Simulating Evolution • Proper simulation of molecular evolution should include both substitutions and indels. • However, existing programs either do not include indels or use an unjustified model of indel formation. • Dawg was created to address this gap. RA Cartwright rac@uga.edu - http://scit.us/

  7. What is Dawg? • Dawg stands for “DNA Assembly with Gaps.” • A portable and robust program for simulating molecular evolution. • Development Website: http://scit.us/dawg/ RA Cartwright rac@uga.edu - http://scit.us/

  8. Comparing Software RA Cartwright rac@uga.edu - http://scit.us/

  9. Parameters • Tree phylogeny • TreeScale coefficient to scale branch lengths by • Sequence root sequences • Length length of generated root sequences • Rates rate of evolution of each root nucleotide • Model model of evolution: GTR|JC|K2P|K3P|HKY|F81|F84|TN • Freqs nucleotide (ACGT) frequencies • Params parameters for the model of evolution • Width block width for indels and recombination • Scale block position scales • Gamma coefficients of variance for rate heterogeneity • Alpha shape parameters • Iota proportions of invariant sites • GapModel models of indel formation: NB|PL|US • Lambda rates of indel formation • GapParams parameter for the indel model • Reps number of data sets to output • File output file • Format output format: Fasta|Nexus|Phylip|Clustal • GapSingleChar output gaps as a single character • GapPlus distinguish insertions from deletions in alignment • LowerCase output sequences in lowercase • Translate translate outputed sequences to amino acids • NexusCode text or file to include between datasets in Nexus format • Seed PRNG seed (integers) RA Cartwright rac@uga.edu - http://scit.us/

  10. Sample Input File # example.dawg Tree = ((AY727331:0.001359,AY727330:0.001359):0.084512, (AY727327:0.006116,AY727326:0.006116):0.079756); Model = "GTR" Params = {1.08031, 2.45581, 0.44452, 1.09145, 4.06519, 1.00000} Freqs = {0.353470, 0.143681, 0.178206, 0.324643} Length = 300 Lambda = 0.143120 GapModel = "NB" GapParams = {1, 0.753247} Format = "Clustal" File = "example.aln" Seed = 1981 RA Cartwright rac@uga.edu - http://scit.us/

  11. CLUSTAL multiple sequence alignment (Created by DAWG Version 1.0.0) AY727326 TTCGAAAATATGTTAGTACTCAATATGAATTCTTTGAGTTAAAAAAGATAAAGCAAA--A AY727327 TTCGAAAATATGTTAGTACTCAATATGAATTCTTTGAGTTAAGAAAGATAAAGCAAA--A AY727330 TTCAAAAATATGCTAGGACTGAATATGAATTCTTAAAGTTAAGAAAGATAAAGAAAAACA AY727331 TTCAAAAATATGCTAGGACTGAATATGAATTCTTAAAGTTAAGAAAGATAAAGAAAAACA AY727326 ATACATAATGTGATTTCAATATTCCAATTACCTAACAATACGGCTATCAATTAAACGATT AY727327 ATACATAATGTGATTTCAATATTCCAATTACCTAACAATACGGCTATCAATTAAACGATT AY727330 GTACATAATGTAAA----TTATTGCAA---------AAAACGGCTAACAATTAGACGATT AY727331 GTACATAATGTAAA----TTATTGCAA---------AAAACGGCTAACAATTAGACGATT AY727326 TTAGGATTACACCGACAAATATTAGGCCGATATGAATTTAACATCATGTTGTATTTAGAT AY727327 TTAGGATTACACCGACAAATATTAGGCCGATATGAATTTACCATCATGTTGTATTTAGAT AY727330 TTAGGATTACGCTGACAAATATTAGGATGATATTAATTTA------TCTTGTATTTAGAT AY727331 TTAGGATTACGCTGACAAATATTAGGATGATATTAATTTA------TCTTGTATTTAGAT AY727326 GCTGTCTTTTATTAACATTCATCATTAAAT-TTGGAACCTTTTGCATTTAAGAAGTACAT AY727327 GCTGTCTTTTATTAACATTCATCATTAAAT-TTGGAACCTTTTGTATTTAAGAAGTACAT AY727330 GCTGTCTTTTATCAACATTCATCACTAGATATTGGAACCTATTGCATCTAAGAAGTACAT AY727331 GCTGTCTTTTATCAACATTCATCACTAGATATTGGAACCTATTGCATCTAAGAAGTACAT AY727326 GTTTAATAGTGTTTAAAA-TATATATGAAATTGATCATAAGGA---TCTATAAATGCGGT AY727327 GTTTAATAGTGTTTATAA-TATATATGAAATTGATCGTAAGGA---TCTATAAATGCAGT AY727330 GTTTAATAGGGTT-AAAACTATATATGAAGTCGATTATAAGGAATTTCTATAAATGTAGC AY727331 GTTTAATAGGGTT-AAAACTATATATGAAGTCGATTATAAGGAATTTCTATAAATGTAGC AY727326 TCTTCAATTTCTTG AY727327 TCTTCAATTTCTTG AY727330 TCTTCAATTTCCTA AY727331 TCTTCAATTTCCTA RA Cartwright rac@uga.edu - http://scit.us/

  12. Estimating Indel Rate • Dawg would be of little benefit if biologists could not estimate parameters of indel formation from real data. • Dawg’s indel model allows such estimation, which is implemented in a Perl script, lambda.pl. RA Cartwright rac@uga.edu - http://scit.us/

  13. Example Usage:Confidence Interval of Indel Rate • I aligned the sequences of chloroplast trnK introns from two Hibiscus and two Prunus species. • Using Paup*, I estimated the phylogeny and substitution parameters. • Using lambda.pl, I estimated the indel formation parameters. RA Cartwright rac@uga.edu - http://scit.us/

  14. Example Usage • From these estimated parameters of evolution, I constructed an input file for Dawg. • From the input file Dawg produced a thousand simulated sequence sets. • The rate of indel formation was estimated for each of the simulated sequences. RA Cartwright rac@uga.edu - http://scit.us/

  15. Results • The estimated rate of indel formation was 0.143120. • Bootstrapping gave a 95% CI of 0.078530 to 0.213560. • Biologically this is 8 to 21 indels per 100 substitutions. RA Cartwright rac@uga.edu - http://scit.us/

  16. Synopsis • Explain the importance of simulations. • Introduce Dawg, a new sequence simulation program. • Example usage of Dawg. RA Cartwright rac@uga.edu - http://scit.us/

  17. Marjorie Asmussen Wyatt Anderson John Avise Jim Hamrick Ron Pulliam Paul Schliekelman Jeff Ross-Ibarra Beth Dakin Douglas Theobald Yong-Kyu Kim Thanks RA Cartwright rac@uga.edu - http://scit.us/

More Related