An online phylogenetic resource for plant gene function prediction

1. Phoenix Bioinformatics
Workshop
Part 2: PhyloGenes, a new
online phylogenetic resource for
plant gene function inference
Peifen Zhang
Phoenix Bioinformatics
2/26/2020

2. Outline
• What is phylogenetic function inference
• Introduction of PhyloGenes
• basic features
• A case study of phylogenetic function inference using PhyloGenes
• How can you search PhyloGenes
• what if your gene is not in PhyloGenes
• Future development

3. A DNA/protein sequence
Function?
Functional annotation

4. A DNA/protein sequence
Predicted function
Relying solely on
sequence similarity
(e.g. BLAST, InterProScan)
Relying on
evolutionary history
(e.g. GO Phylogenetic
Annotation)
Functional annotation

5. Phylogenetic function inference
Evolutionary history of a family of homologs:
human_gene_2
mouse_gene_2
human_gene_3
mouse_gene_3
mouse_gene_3’
human_gene_1
mouse_gene_1
speciation
duplication
ortholog: related by speciation
paralog: related by duplication
paralog: related by duplication
The ortholog conjecture:
Protein function changes rapidly after duplication,
leading to paralogs with different functions, while
orthologs retain the ancestral function.

6. Phylogenetic function inference
Evolutionary history of a family of homologs:
human_gene_2
mouse_gene_2
human_gene_3
mouse_gene_3
mouse_gene_3’
human_gene_1
mouse_gene_1
speciation
duplication motion
pigment
???

7. Phylogenetic function inference
Assigning function from a known gene to
an unknown gene using evolutionary
history of the genes
• orthologs
• known functions of the orthologs

8. phylogenes.org
• Displays phylogenetic trees of gene families across species
• Displays experimentally validated gene function (known function)
and other gene info alongside gene trees
• Facilitates inference of unknown gene function

9. Gene tree
(PANTHER March 2019 release)
Gene info
Family
info
A gene family page

10. • Classification of genes (protein sequence) to gene families
using the PANTHER pipeline (GIGA algorithm)
• 132 genomes across all kingdoms (March 2019 release)
• Led by Paul Thomas at USC
40 genomes (plant-centric)

11. Basic features on a PhyloGenes gene tree
Node
types
Gene name and species name
Taxonomic range of a collapsed
internal node
Subfamily:

12. ‘Known function’
‘GO molecular
function’
supported by
Experimental evidence
(EBI GOA)
A distinct function
found in at least one
member of the
family

13. Toggle to see MSA

14. Tree pruning –hide species and genes from a
gene tree to focus on genes of your interest

15. A tree with 516 genes from
37 organisms
A user choose to only see genes
from Arabidopsis and soybean
The pruned tree

16. Outline
• What is phylogenetic functional inference
• Introduction of PhyloGenes
• basic features
• A case study of phylogenetic functional inference using PhyloGenes
• How can you search PhyloGenes
• what if your gene is not in PhyloGenes
• Future development

18. fatty acid-CoA ligase
4-coumarate-CoA ligase

19. • What you can use
• UniProt IDs, Gene IDs, Gene names, keywords
(Zm00001d007662, Solyc02g086750.1, det2, transporter)
Ways to search PhyloGenes

20. Not finding your gene?
Clipart Library

21. one sequence at a time

22. The TreeGrafter runs HMM scoring to find the best matching gene
family, and RAxML to place the query sequence to the best location
of the tree without changing its existing topology.
The tool was developed primarily for functional inference, the
propagation of functions from an ancestor node to the grafted leaf
node, not for evolutionary inference.
Sometimes, the node that includes the grafted sequence does not
display the complete evolutionary history of its children.
P00875 (spinach)
11436400 (M. truncatula)
Grafted (spinach)
Expected
11411876 (M. truncatula)
25479308 (M. truncatula)
25479326 (M. truncatula)

23. Download
• A gene tree in PNG or SVG image format – can be used in
presentations
• A gene tree in PhyloXML format – can be viewed in other tree
software
• Gene information in CSV format –can be sorted and manipulated in
spread sheet

24. New features in future releases
• Other types of gene function info
• ‘GO biological process’ annotations (experimentally supported)
• Phylogenetically inferred annotations
• more…
Long term
• Enable genome-scale phylogenetic functional annotations
• Display annotated ancestral functions within gene trees
• Enable viewing user upload gene tree or gene function data

25. Thanks to the Phoenix Bioinformatics Team:
Peifen
Erica
Leonore
Tanya
Shabari
Amina
Connie
Laura
Eva
Trilok
Swapnil
Xingguo
Qian
and the USC Team:
Paul Huaiyu Anushya Dustin

26. Hands-on session

27. Find the gene family that has the maize gene Zm00001d017728
Find its ortholog with the known function polyamine transporter
What is the evidence that supports that known function?
Expand the tree so that you can see all genes of maize
Make a pruned view of the tree for your interested species-only
(rice, maize, Arabidopsis)