Pathway Signature Genes

Pathway prediction in (meta)genomes usingPathway Signature Genes
Lucas Brouwers, MSc student, Nijmegen

Goal
How to predict the metabolic capacity in a metagenomic sample, given incomplete data?Current practice:
Percentage of sequences assigned to pathways used for estimating pathway abundance
2 out of 5 sequences map to pathway X:Abundance of X is 40%
We propose to identify the (metabolic) pathways present in a community, making fulluse of the metagenomic data available

Approach
We use presence of OGs to predict presence of pathways
Some species have pathway X
X
X
X
X
OG A
OG C
X
OG B
PWY X
X
PresenceSignature
Weak Signature
AbsenceSignature

Approach
630 species and their OGs
1,200 (metabolic) pathways

Signature genes add information
Do the signatures add information on the presence of a pathway?
(after all some pathways are rare, others are ubiquitous)
Specific information defined as a difference in Shannon entropy: how much extra information does the presence of an OG give about the presence of a pathway?

What makes a signature?
N = 29,661
N = 46,176,543

Absence signatures in a pathway
COG0437 (221 species): Fe-S-cluster-containing hydrogenases
Formatedehydrogenase
Formylmethanofuran-dehydrogenase
Glycolaldehyde-dehydrogenase
Nitrate reductase

Integrate signature scores with pathway prediction in metagenomes
For quantitative analysis of pathways in metagenomic samples:
Consider Chlorphyll biosynthesis:Sa: Average of all OG scores, of OGs in species without chlorophyll biosynthesis
Sp: Average of all OG scores, of OGs in species with …
Si: Average of all OG scores found in a metagenomic sample
Correcting for genome sizes becomes …

Performance in sub-sampling
Sample percentage of OGs from every species in STRING
Predict percentage of species with pathway & compare with actual occurrence

Application to metagenomes
Dinsdale, E. A., Edwards, R. A., Hall, D., Angly, F., Breitbart, M., Brulc, J. M., et al. (2008). Functional metagenomic profiling of nine biomes. Nature, 452 (7187), 629-32.
Different biomes:
Subterranean
Hypersaline
Freshwater
Fish
Coral
Marine

Simulated metagenomes
Sample OGs according to species distribution in metagenome
Predict percentage of species with pathway & compare with actual occurrence
Sampling 1%

Pathway description of biome diversity
Pathway occurrence was predicted in 35 metagenomic datasets
Principal component analysis revealed the pathways responsible for differences between the biomes

Conclusions
Pathway signature genes allow us to interpret biomes on a pathway level
Genes do not need to be part of a pathway to predict its presence
We can quantitatively and accurately describe the pathway content of a metagenome

Acknowledgements
Bas E Dutilh
MartijnHuynen

http://bytesizebio.net	922
http://www.lucasbrouwers.nl	13
http://www.slideshare.net	5

Pathway Signature Genes

by NCMLS on Jul 06, 2009

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