MStruct: Structure under mutations Suyash Shringarpure and Eric Xing Carnegie Mellon University...
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![Page 1: MStruct: Structure under mutations Suyash Shringarpure and Eric Xing Carnegie Mellon University mStruct: Inference of population structure in the presence.](https://reader035.fdocuments.us/reader035/viewer/2022062421/56649d375503460f94a0f23a/html5/thumbnails/1.jpg)
mStruct: Structure under mutations
Suyash Shringarpure and Eric XingCarnegie Mellon University
mStruct: Inference of population structure in the presence of genetic
admixing and allele mutations
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Significance
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Genetic Population Structure
• Structure (Pritchard et al, 2000)
Genetic structure of Human Populations (Rosenberg et al. 2002)
Africa Europe Mid-East Cent./S. Asia East Asia Oceania
Ancestral proportion
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Generative model- Structure
0.3 0.7
0.8 0.2
α (for the dataset)
0.8 0.2
All the alleles observed at this locus
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Modeling allele similarity
• Microsatellite– Repeats of a small DNA unit, say
Allele - 2
Allele - 9
Allele - 10
•Allele 9 is much more similar to allele 10 than allele 2.•Allele 10 might be a mutation of allele 9.•Mathematically encode the idea in the model•mStruct – Structure under mutations
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Hypothesis
• Individual genomes in modern populations are a result of– Admixture of ancestral populations.– Mutations from ancestral alleles.
• Ancestral populations have fewer alleles– (Mostly) True for microsatellites
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Generative model- mStruct
0.3 0.7
0.8 0.2
α (for the dataset)
0.8 0.2
All the alleles observed at this locus
δ1
δ2
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Mutation models
• How to derive descendant alleles from ancestral alleles?
• Distribution based on the single step model
• P(b|a) α δabs(b-a) , δ < 1• Computationally “easy”• NOT conventional mutation rate.
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Finding ancestral alleles
• Fit mixtures of mutation distributions
• Try using 1,2,3….. ancestral alleles
• Use information theory to decide how many ancestral alleles are appropriate
Histogram of observed alleles
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Comparing population structure maps
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Phylogenetic Trees from the Structural Maps
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Phylogenetic Trees from the Structural Maps
mStruct Structure
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HGDP SNP results
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Implications of Inconsistency
• Simplistic mutation model• SNP mutations harder to discover from data• The model reduces to Structure• Fundamental difference– Different markers treated differently
• Structure’s treatment of alleles is almost categorical
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Contour of Empirical Mutation
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Conclusion
• Generative model for population structure• Modeling mutations from ancestral alleles• Gives mutational information apart from
population structure.• (in press) Genetics• Online version up now.
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Graphical model representations
Structure mStruct