gsr the gene sequence evolution model with iid rate variation over tree Örjan Åkerborg, kth lars...

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GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad

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Page 1: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad

GSRThe Gene Sequence evolution model

with iid Rate variation over tree

Örjan Åkerborg, KTH

Lars Arvestad, KTH

Jens Lagergren, KTH

Bengt Sennblad

Page 2: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad

What?

• Gene evolution through duplication and loss

• Sequence evolution

Page 3: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad

Why?

• Base reconciliation analysis directly on data– Avoid information loss– Addresses uncertainty better

• Gene tree reconstruction should mirror generation

Page 4: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad

When?

• Arvestad et al. 2003, – MrBayes + GEM– Flawed model

Page 5: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad

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60s ribosomal data

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Page 6: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad

• Arvestad et al. 2003, – MrBayes + GEM– Flawed model

• Arvestad et al. 2004 – Intergrated GEM + Substitution model– Mathematically correct model– Molecular clock– Sampling algorithm - slow

When?

Page 7: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad

MHC revisited

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Page 8: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad

• Åkerborg et al. Submitted (GSR)– Integrated GEM + SRT model

When?

• Arvestad et al. 2003, – MrBayes + GEM– Flawed model

• Arvestad et al. 2004– Intergrated GEM + Substitution model– Mathematically correct model– Molecular clock– Sampling algorithm - slow

Page 9: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad

How?

• GSR– GEM

• Reconciled trees – duplication and loss

– SRT• Relaxed clock model (iid)• Substitution model

– Fast algorithm• Discretized time space

Page 10: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad

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Trees, T

Sequence data, F

Pr[D,T]

Self-consistency

Page 11: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad

Self-consistency – the X%-test

Page 12: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad

Application to Yeast data

• Compare to prev. Results– YGOB– Orthogrups (SYNERGY)

• Both synteny-based

Page 13: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad

Synteny -- gene order

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Page 14: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad

Application to Yeast data

• Compare to prev. Results– YGOB– Orthogrups (SYNERGY)

• Both synteny-based

– Whole genome duplication• Challenge!

• Genome-wide analysis!– 4809 gene families

(orthogroups)

Page 15: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad

Comparison YGOB results

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Page 16: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad

Molecular clock?

Page 17: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad

Comparison SYNERGY results

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Page 18: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad

Sequence vs. synteny data

• No sequence diff– 36% of data sets are >85% similar

• Strong divergence– 25% of data set are <40% similar– Long-branch attraction

• Conflicting sequence-synteny signal

Page 19: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad

Sequence vs. synteny data

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Page 20: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad

Orthogroup 3176

42.4 %

Single best SYNERGY tree

21.6 %31.6 %

Page 21: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad

Summary

• primeGSR– Integrated model

• Reconciliation – gene duplication loss• Relaxed clock• Sequence evolution

– Efficient algorithms– Improved gene tree reconstruction

• Future prospects– Divergence time estimates (MAP)– Species tree reconstruction– Include synteny