Phylogenetic prediction of gene function

Daniel BarkerCentre for Evolution, Genes and Genomics,

School of Biology,

University of St Andrews

http://biology.st-andrews.ac.uk/cegg

1 0 1 0 1 0 1 01 0 1 0 1 0 1 0

1 1 1 1 0 0 0 01 1 1 1 0 0 0 0

1 0 1 0 1 0 1 01 0 1 0 1 0 1 0

1 1 1 1 0 0 0 01 1 1 1 0 0 0 0

Gene A 1 0 1 0 1 0 1 0Gene B 1 0 1 0 1 0 1 0

Gene C 1 1 1 1 0 0 0 0Gene D 1 1 1 1 0 0 0 0

sp. i

sp. i

i

sp. i

ii

sp. i

v

sp. v

sp. v

i

sp. v

ii

sp. v

iii

Correlations in gene gain/loss

0.1

S. cerevisiaeS. paradoxus

S. mikatae

S. bayanus

S. castellii

Saccharomyces kluyveri

Candida albicans

Schizosaccharomyces pombe

Fusarium graminearum

Neurospora crassa

Magnaporthe griseaAspergillus nidulans

Cryptococcus neoformans

Drosophila melanogaster

Caenorhabditis elegans

1 1 0 0

1 1 0 0

1 1 0 0

1 1 0 0

1 1 0 0

1 1 1 11 1 1 1

0 1 1 1

0 0 0 1

0 0 0 1

0 0 1 1

0 0 0 1

0 0 0 1

0 0 0 1

0 0 0 1

CIN4

ORC3L9A

L42B

0.1 changesper nucleotide

The ‘traditional’ across-species method of phylogenetic profiles (Pellegrini et al. 1999, PNAS 96: 4285–7288) returns a false positive functional link for the pair of proteins {CIN4, ORC3} and a false negative for the pair {L9A, L42B}. The tree-based, maximum likelihood phylogenetic method returns the ‘correct’ result for both pairs (Barker & Pagel 2005, PLoS Comp Biol 1:24–31).

Example

1.0 0.5

0.2

0.1

0.0

5

0.0

1

0.0

05

0.0

01

0.0

009

0.0

008

0.0

007

0.0

006

0.0

005

0.0

004

0.0

003

0.0

002

p-value cut-off

30

40

50

60

70

80

90

100

20

% s

pec

ific

ity

Validation

Test data based on known yeast protein complexesIn the Comprehensive Yeast Genome Database(http://mips.gsf.de/genre/proj/yeast)

University of Reading:Mark PagelAndrew Meade

Wellcome Trust Sanger Institute:Valerie Wood

(UCL):Antonio Cavallo

Funding:BBSRC

EPSRC on behalf of Research Councils UK

Acknowledgements