New methods for estimating - PowerPoint Presentation

Slide1

New methods for estimating species trees from genome-scale data

Tandy WarnowThe University of Illinois

Slide2

Orangutan

Gorilla

Chimpanzee

Human

From the Tree of the Life Website,

University of Arizona

Phylogeny

(evolutionary tree)

Slide3

Orangutan

Gorilla

Chimpanzee

Human

From the Tree of the Life Website,

University of Arizona

Sampling multiple genes from multiple species

Slide4

Slide5

Incomplete Lineage Sorting (ILS) is a dominant cause of

gene tree heterogeneity

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This talkGene tree heterogeneity due to incomplete lineage sorting, modelled by the multi-species coalescent (MSC)

Statistically consistent estimation of species trees under the MSC, and the impact

of gene tree estimation error“Statistical binning” (Science 2014) – improving gene tree estimation, and hence species tree estimation

Open questions

Slide7

Gene trees inside the species tree (Coalescent Process)

Present

Past

Courtesy James

Degnan

Gorilla and Orangutan are not siblings in the species tree, but they are in the gene tree.

Slide8

Incomplete Lineage Sorting (ILS)Confounds phylogenetic analysis for many groups: Hominids, Birds, Yeast, Animals, Toads, Fish, Fungi, etc.

There is substantial debate about how to analyze phylogenomic datasets in the presence of ILS.

Slide9

. . .

Analyze

separately

Summary Method

Two competing approaches

gene 1

gene 2

. . .

gene

k

. . .

Concatenation

Species

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Statistical Consistencyerror

Data

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Slide12

. . .

What about summary methods?

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. . .

What about summary methods?

Techniques:

Most frequent gene tree?

Consensus of gene trees?

Other?

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Statistically consistent under ILS?

Coalescent-based summary methods:MP

-EST (Liu et al. 2010): maximum pseudo-likelihood estimation of rooted species

tree based on rooted triplet tree distribution – YESBUCKy-pop (

Ané and Larget 2010): quartet-based Bayesian species tree estimation –

YESAnd many others (ASTRAL, ASTRID, NJst, GLASS, etc.)

Co-estimation methods: *BEAST (Heled

and Drummond 2009): Bayesian co-estimation of gene trees and species trees

– YESSingle-site methods (SVDquartets, METAL, SNAPP, and others)

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Statistically consistent under ILS?

Coalescent-based summary methods:MP

-EST (Liu et al. 2010): maximum pseudo-likelihood estimation of rooted species

tree based on rooted triplet tree distribution – YESBUCKy-pop (

Ané and Larget 2010): quartet-based Bayesian species tree estimation –

YESAnd many others (ASTRAL, ASTRID, NJst, GLASS, etc.)

Co-estimation methods: *BEAST (Heled

and Drummond 2009): Bayesian co-estimation of gene trees and species trees

– YESSingle-site methods (SVDquartets, METAL, SNAPP, and others) - YES

CA-ML (Concatenation

using unpartitioned

maximum likelihood) - NO

MDC – NO

GC (Greedy Consensus) – NO

MRP (supertree method) –

NO

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Statistically consistent under ILS?

Coalescent-based summary methods:MP

-EST (Liu et al. 2010): maximum pseudo-likelihood estimation of rooted species

tree based on rooted triplet tree distribution – YESBUCKy-pop (

Ané and Larget 2010): quartet-based Bayesian species tree estimation –

YESAnd many others (ASTRAL, ASTRID, NJst, GLASS, etc.)

Co-estimation methods: *BEAST (Heled

and Drummond 2009): Bayesian co-estimation of gene trees and species trees

– YESSingle-site methods (SVDquartets, METAL, SNAPP, and others) - YESCA-ML (Concatenation using unpartitioned

maximum likelihood) -

NO

MDC –

NO

GC (Greedy Consensus) –

NO

MRP (supertree method) –

NO

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Results on 11-taxon datasets with weak ILS

*

BEAST more accurate than summary methods (MP-EST, BUCKy

, etc) CA-ML (concatenated analysis) most accurate Datasets from Chung and

Ané, 2011 Bayzid

& Warnow, Bioinformatics 2013

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Problem: poor gene trees

Summary methods combine estimated gene trees, not true gene trees.

The individual gene sequence alignments in the 11-taxon datasets have poor phylogenetic signal, and result in poorly estimated gene trees.

Species trees obtained by combining poorly estimated gene trees have poor accuracy.

Slide19

Problem: poor gene trees

Summary methods combine estimated gene trees, not true gene trees.

The individual gene sequence alignments in the 11-taxon datasets have poor phylogenetic signal, and result in

poorly estimated gene trees.Species trees obtained by combining poorly estimated

gene trees have poor accuracy.

Slide20

Problem: poor gene trees

Summary methods combine estimated gene trees, not true gene trees.

The individual gene sequence alignments in the 11-taxon datasets have poor phylogenetic signal, and result in poorly estimated gene trees.

Species trees obtained by combining poorly estimated gene trees have poor accuracy.

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Summary methods combine estimated gene trees, not true gene trees.

The individual gene sequence alignments in the 11-taxon datasets have poor phylogenetic

signal, and result in poorly estimated gene trees.Species trees obtained by combining poorly estimated

gene trees have poor accuracy.

TYPICAL PHYLOGENOMICS PROBLEM: many poor gene trees

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Summary methods combine estimated gene trees, not true gene trees.

The individual gene sequence alignments in the 11-taxon datasets have poor phylogenetic

signal, and result in poorly estimated gene trees.Species trees obtained by combining poorly estimated

gene trees have poor accuracy.

THIS IS A KEY ISSUE IN THE DEBATE ABOUT HOW TO COMPUTE SPECIES TREES

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Statistical Consistency for summary methods

error

Data

Data are gene trees, presumed to be randomly sampled

true gene trees.

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Avian Phylogenomics Project

E

Jarvis,

HHMI

G

Zhang,

BGI

Approx. 50 species, whole

genomes, 14,000 loci

Published Science 2014

MTP Gilbert,

Copenhagen

S.

Mirarab

Md

. S.

Bayzid

, UT-

Austin UT-Austin

T. WarnowUT-Austin

Plus many many other people…

Challenges:Massive gene tree conflict suggestive of ILSCoalescent-based analysis using MP-EST produced tree that conflicted with concatenation analysisMost gene trees had very low bootstrap support, suggestive of gene tree estimation

error

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Avian Phylogenomics Project

E

Jarvis,

HHMI

G

Zhang,

BGI

Approx. 50 species, whole

genomes, 14,000 loci

MTP Gilbert,

Copenhagen

S.

Mirarab

Md

. S.

Bayzid

, UT-

Austin UT-Austin

T. Warnow

UT-Austin

Plus many many other people…Solution:

Statistical BinningImproves coalescent-based species tree estimation by improving gene trees (Mirarab, Bayzid, Boussau, and Warnow, Science 2014

)Avian species tree estimated using

Statistical Binning with MP-EST

(Jarvis, Mirarab, et al.,

Science

2014)

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Gene Tree Estimation Error can be due to insufficient data

error

Data

Data are sites in an alignment for a c-gene

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Unweighted statistical binning (Science 2014)

Given multiple sequence alignments for a set of loci:

Estimate ML gene trees with bootstrap support Bin genes based on gene tree compatibility after collapsing low support branches, producing “supergene alignments”

Compute “supergene trees” (one for each bin), using fully partitioned maximum likelihoodApply coalescent-based summary method to the supergene trees, requiring that the summary method be statistically consistent under the MSC

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Unweighted statistical binning pipelines are not statistically consistent under GTR+MSC

Easy proof: As the number of sites per locus increaseA

ll estimated gene trees converge to the true gene tree and have bootstrap support that converges to 1 (Steel 2014)For every bin, with probability converging to 1, the genes in the bin have the same tree topology.Fully partitioned GTR ML analysis of each bin converges to a tree with the common topology of the genes in the bin.

As the number of loci increase, every gene tree topology appears with probability converging to 1.Cannot infer the species tree from the flat distribution of gene trees!

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Weighted statistical binning (PLOS One 2015)

Given multiple sequence alignments for a set of loci:

Estimate ML gene trees with bootstrap support Bin genes based on gene tree compatibility after collapsing low support branches, producing “supergene alignments”

Compute “supergene trees” (one for each bin), using fully partitioned maximum likelihood

Replace original gene tree by the new supergene tree (equivalently, replicate supergene trees by the size of each bin)Apply coalescent-based summary method to the supergene trees, requiring that the summary method be statistically consistent under the MSC

Slide30

WSB pipelines are statistically consistent under GTR+MSCEasy proof:

As the number of sites per locus increaseAll estimated gene trees converge to the true gene tree and have bootstrap support that converges to 1 (Steel 2014)

For every bin, with probability converging to 1, the genes in the bin have the same tree topology Fully partitioned GTR ML analysis of each bin converges to a tree with the common topology of the genes in the bin

Hence as the number of sites per locus and number of loci both increase, WSB followed by a statistically consistent summary method will converge in probability to the true species tree. Q.E.D.

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Statistical binning vs. unbinned

Mirarab, et al., Science 2014 (Unweighted statistical binning)

Binning produces bins with approximate 5 to 7 genes each

Datasets: 11-taxon strongILS datasets with 50 genes, Chung and Ané, Systematic Biology

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Comparing Binned and Un-binned MP-EST on the Avian Dataset

Unbinned

MP-ESTs

trongly rejects Columbea, a majorfinding by Jarvis, Mirarab,et

al.Binned MP-EST islargely consistent with the MLconcatenation

analysis.The trees presentedin Science 2014 werethe ML concatenationa

nd Binned MP-EST

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Summary

Unpartitioned concatenation using maximum likelihood is statistically inconsistent under the MSC (Roch and Steel 2014, see discussion in Warnow PLOS Currents 2015)

Gene tree estimation error impacts species tree estimation (multiple papers)Statistical binning (Mirarab et al. Science 2014) improves coalescent-based species tree estimation from multiple genes, used in Avian Tree (Jarvis, Mirarab, et al. Science 2014).Weighted statistical binning pipelines are statistically consistent under GTR+MSC, but unweighted statistical binning pipelines are not (Bayzid et al., PLOS One 2015)

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Bounded number of sites per locus?Do any summary methods converge to the species tree as the number of loci increase, but where each locus has only a constant number of sites?

Roch & Warnow, Systematic Biology 2015

:Yes under the strong molecular clock (even for a single site per locus)Very

limited results otherwise

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Open QuestionsIs fully partitioned ML statistically consistent or inconsistent under the MSC? (Note: proof by

Roch and Steel for unpartitioned ML will not easily extend to fully partitioned)

Are any of the standard summary methods statistically consistent for bounded number of sites per locus, but unbounded number of loci?Are the co-estimation methods (e.g., *BEAST and BEST) statistically consistent for bounded number of sites per locus but unbounded number of loci?

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Open QuestionsWhy does concatenation using ML (whether unpartitioned or partitioned) produce such good accuracy under many conditions?

Why does statistical binning improve accuracy under many conditions?

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Acknowledgments

PhD students: Siavash Mirarab* (now Assistant Professor at UCSD ECE) and Md. S. Bayzid**

Bastien

Boussau

(CNRS, Lyon)

Sébastien

Roch

(Wisconsin)

Funding

: Guggenheim Foundation, Packard, NSF, Microsoft Research New England, David

Bruton

Jr. Centennial Professorship, TACC (Texas Advanced Computing Center), and GEBI.

TACC

and UTCS

c

omputational resources

* Supported by HHMI Predoctoral Fellowship

** Supported by Fulbright Foundation Predoctoral Fellowship