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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: ,[object Object],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 ,[object Object]
 Predict percentage of species with pathway & compare with actual occurrence,[object Object]
Hypersaline
 Freshwater
 Fish
 Coral
 Marine,[object Object]

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Pathway Signature Genes

  • 1. Pathway prediction in (meta)genomes usingPathway Signature Genes Lucas Brouwers, MSc student, Nijmegen
  • 2.
  • 3. 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
  • 4. Approach 630 species and their OGs 1,200 (metabolic) pathways
  • 5. 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?
  • 6. What makes a signature? N = 29,661 N = 46,176,543
  • 7. Absence signatures in a pathway COG0437 (221 species): Fe-S-cluster-containing hydrogenases Formatedehydrogenase Formylmethanofuran-dehydrogenase Glycolaldehyde-dehydrogenase Nitrate reductase
  • 8. 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 …
  • 9.
  • 10.
  • 15.
  • 16. Predict percentage of species with pathway & compare with actual occurrenceSampling 1%
  • 17. 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
  • 18. 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
  • 19. Acknowledgements Bas E Dutilh MartijnHuynen