New methods diploid assembly with graphs

New methods diploid assembly with graphs

• 1.
  A cost-effective approachto diploid genome assembly using sequence graphs Shilpa Garg Postdoc Church lab Harvard Medical School 1
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  Diploid genome assembly AC G T C T C C G T A T C G T A C G T A T T A C G T A T C C G T A T G T Input: Reads Diploid assemblies Applications: ● Personalized medicine ● Human migration, evolutionary selection and population structure 2
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  Different approaches Reference-based haplotyping Referencegenome Aligned reads Haplotypes Drawbacks ● Reference bias ● Does not work for structural variants (SVs) Tools: WhatsHap, HapCut, HapCol 3
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  De novo assembly Differentapproaches Reference-based haplotyping Reference genome Aligned reads Haplotypes Drawbacks ● Reference bias ● Does not work for structural variants (SVs) r1 r2 r3 r4 r5 r1 r2 r3 r4r5 Assembly graph Reads Tools: WhatsHap, HapCut, HapCol 4
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  De novo assembly Differentapproaches Reference-based haplotyping Reference genome Aligned reads Haplotypes Drawbacks ● Reference bias ● Does not work for structural variants (SVs) r1 r2 r3 r4 r5 r1 r2 r3 r4r5 Assembly graph assembly Reads Tools: WhatsHap, HapCut, HapCol 6
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  De novo assembly Differentapproaches Reference-based haplotyping Reference genome Aligned reads Haplotypes Drawbacks ● Reference bias ● Does not work for structural variants (SVs) Drawbacks ● Assumption: haploid assembly ● Require high coverage data r1 r2 r3 r4 r5 r1 r2 r3 r4r5 Assembly graph assembly Reads Tools: WhatsHap, HapCut, HapCol Tools: Genome assembly: Canu, SPAdes… Diploid genome assembly: Falcon Unzip, TrioCanu 7
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  Why graph-based approach? SNVSV SV SNV 8
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  Phasing bubble chains SNVSV SV SNV 9
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  Phasing bubble chains SNVSV SV SNV 10
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  Our diploid assemblypipeline 11 Single individual
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  Our diploid assemblypipeline 12 Single individual Trios
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  Advantages - Generalized tobe applied to genomes of any complexity - Different het rate and repeat content - Phase complex SVs 13
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  Results We require aslow as 15x coverage of long reads from each individual in a trio 14
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  Conclusion - Apply pipelineon GIAB trio samples from PGP - Fill gaps in PGP-1 genome and other variety of samples - Apply haplotype-aware assembly to diverse human genomes, including clinically relevant regions, to understand complex biology 16 - Developed pipeline for diploid assembly for single individuals and trios - Demonstrated on genomes with various het rate Next steps: Open for collaborations and recruiting people at Church lab
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  Acknowledgements George Church Tobias Marschall RichardDurbin ... 17
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  18 Thanks