Supertrees: Algorithms and Databases

1. Supertrees: Algorithms and Databases Roderic Page University of Glasgow r.page@bio.gla.ac.uk DIMACS Working Group Meeting on Mathematical and Computational Aspects Related to the Study of The Tree of Life

2. What do we mean by the “Tree of Life” Our perception of what the tree is may affect what we view as being the “interesting” problems or Tree algorithms, models, genomics, lateral gene transfer Supertrees, datatypes, databases, taxonomy

3. Topics • Supertrees (MinCut) • Phylogenetic databases

4. Tree terminology d a b c leaf { a,b } edge internal node cluster { a,b,c } root { a,b,c,d }

5. Nestings and triplets d a b c Nestings {a,b} <T {a,b,c,d} {b,c} <T {a,b,c,d} Triplets (bc)d bc|d

6. Supertree d a b c a b c b c d = + T T 1 2 supertree

7. Some desirable properties of a supertree method(Steel et al., 2000) • The supertree can be computed in polynomial time • A grouping in one or more trees that is not contradicted by any other tree occurs in the supertree

8. Aho et al.’s algorithm (OneTree) Aho, A. V., Sagiv, Y., Syzmanski, T. G., and Ullman, J. D. 1981. Inferring a tree from lowest common ancestors with an application to the optimization of relational expressions. SIAM J. Comput. 10: 405-421. Input: set of rooted trees 1. If set is compatible (i.e., will agree on a tree), output that tree. 2. If set is not compatible, stop!

9. a b a a b b a, b c a, b, c, d a, b, c d d c c a b c b c d Aho et al.’s OneTree algorithm T T 1 2 supertree

10. Mincut supertrees Semple, C., and Steel, M. 2000. A supertree method for rooted trees. Discrete Appl. Math. 105: 147-158. • Modifies OneTree by cutting graph • Requires rooted trees (no analogue of OneTree for unrooted trees) • Recursive • Polynomial time

11. b a c e d a b c d e a b c d T T 1 2 S { T , T } 1 2 Semple and Steel (2000)

12. Collapsing the graph(Semple and Steel mincut algorithm) This edge has maximum weight b a,b 2 1 1 c a c 1 1 1 e d e d 1 1 max S S / E { T , T } { T , T } { T , T } 1 2 1 2 1 2

13. Cut the graph to get supertree a,b a b c d e 1 c 1 e d 1 max S / E { T , T } { T , T } 1 2 1 2 supertree

14. My mincut supertree implementationdarwin.zoology.gla.ac.uk/~rpage/supertree • Written in C++ • Uses GTL (Graph Template Library) to handle graphs (formerly a free alternative to LEDA) • Finds all mincuts of a graph faster than Semple and Steel’s algorithm

15. A counter example: two input trees... a c b b a c y 1 x 1 y 2 x 2 y 3 x y 3 4

16. Mincut gives this (strange) result • Disputed relationships among a, b, and c are resolved • x1, x2, and x3 collapsed into polytomy c x 1 x 2 x 3 b a y 1 y 2 y 3 y 4

17. S { T , T } 1 2 Problem:Cuts depend on connectivity(in this example it is a function of tree size) y4 x3 y1 x2 b y2 x1 y3 c a

18. So, mincut doesn’t work • But, Semple and Steel said it did • My program seems to work • Argh!!! What is happening….?

19. What mincut does… …and does not do • Mincut supertree is guaranteed to include any nesting which occurs in all input trees • Makes no claims about nestings which occur in only some of the trees • “Does exactly what it says on the tin™”

20. Modifying mincut supertree • Can we incorporate more of the information in the input trees? • Three categories of information • Unanimous (all trees have that grouping) • Contradicted (trees explicitly disagree) • Uncontradicted (some trees have information that no other tree disagrees with)

21. Uncontradicted informationassume we have k input trees a and b co-occur in a tree a and b nested in a tree n c a b a b c - n = 0  uncontradicted (if c = k then unanimous) c - n > 0  contradicted

22. Uncontradicted informationassume we have k input trees a and b in a fan a and b co-occur in a tree a and b nested in a tree f n c a b a b a b c - n -f = 0  uncontradicted (if c = k then unanimous) c - n - f > 0  contradicted

23. Classifying edges S { T , T } 1 2 y x 1 1 y y 1 2 x x y 2 1 2 y y x 3 4 2 x 3 b y b 4 y x 3 3 c a a c Uncontradicted Uncontradicted but adjacent to contradicted Contradicted

24. Modified mincut • Species a, b, and c form a polytomy • x1, x2, and x3 resolved as per the input tree modified mincut a b c x 1 x 2 x 3 y 1 y 2 y 3 y 4

25. 1 1 1 1 2 2 2 2 3 3 3 3 4 4 4 4 5 5 5 5 If no tree contradicts an item of information, is that information always in the supertree? (23)5 (12)5 (45)1 (34)1

26. 1 2 3 4 5 No!Steel, Dress, & Böcker 2000 • The four trees display (12)5, (23)5, (34)1, and (45)1 • No tree displays (IK)J or (JK)I for any (IJ)K above • Triplets are uncontradicted, but cannot form a tree

27. Future directions for supertrees • Improve handling of uncontradicted information • Add support for constraints • Visualising very big trees • Better integration into phylogeny databases (www.treebase.org) darwin.zoology.gla.ac.uk/~rpage/supertree

28. Supertree Challenge (proposed by Mike Sanderson mjsanderson@ucdavis.edu) The TreeBASE database currently contains over 1000 phylogenies with over 11,000 taxa among them. Many of these trees share taxa with each other and are therefore candidates for the construction of composite phylogenies, or "supertrees", by various algorithms. A challenging problem is the construction of the largest and "best" supertree possible from this database. "Largest" and "best" may represent conflicting goals, however, because resolution of a supertree can be easily diminished by addition of "inappropriate" trees or taxa.

29. It’s a scandal • We cannot answer even the most basic question: “what is the phylogeny for group x?” • GenBank is currently the best phylogenetic database (!) • Can't even say how many species are in a given group • Little idea of who is doing what

31. Tree of Lifetolweb.org • Provides text and images • Relies on extensive manual effort (e.g., writing text) • Can’t do any computations with it • Limited research value

32. TreeBASEwww.treebase.org • Relational database • Query by author, taxon, study number • Compute supertrees • Submit NEXUS data files

33. TreeBASE

34. TreeBASE and mincut supertrees • User selects two or more trees • Clicks on button and script on darwin.zoology.gla.ac.uk is run to create supertree • Can view as PS, PDF, treefile, or in Java applet (ATV)

35. What’s wrong with TreeBASE? • No consistency of taxon names • (e.g., Human, Homo sapiens, Homo sapiens X54666-1) • No consistency of data names (e.g., gene names, morphological characters, etc.)

36. The same organism may have multiple names

37. www.all-species.org “The ALL Species Foundation is a non-profit organization dedicated to the complete inventory of all species of life on Earth within the next 25 years - a human generation.” Press Release: November 13, 2002 Starting December 1, the ALL Species Foundation will close its San Francisco office because of a lack of funding for the Foundation.

38. The first challenge • We need a taxonomic name server that can resolve the name of any organism • This server needs to reconcile multiple classifications (e.g., GenBank, ITIS, etc.) • Must handle at least 1 million names, perhaps 100 million

39. Second Challenge • How do we query trees? • Trees can be classifications or phylogenies

40. SQL Queries on Trees • Oracle SQL Transitive Closure Query (recursion) • Nested queries • Node path queries

41. 1. All ancestors of node A A

42. 2. Least Common Ancestor (LCA) of A and B A B

43. 3. Spanning Clade of A and B A B

44. 4. Path Length from A and B A B 5

46. Node paths /1/1/2 /1/2/1 /1/2/2 /1/1/1/2 /1/1/1/1 /2 /1/1/1 /1/2 /1/1 /1

47. Node paths - selecting subtree /1/1/2 /1/2/1 /1/2/2 /1/1/1/2 /1/1/1/1 /2 /1/1/1 /1/2 /1/1 /1 SELECT node WHERE (path LIKE “/1/1/%”) AND (path < “/1/10/%”);

48. Node paths - selecting subtree /1/1/2 /1/2/1 /1/2/2 /1/1/1/2 /1/1/1/1 /2 /1/1/1 /1/2 /1/1 /1 SELECT node WHERE (path LIKE “/1/1/%”) AND (path < “/1/10/%”) AND (num_children IS 0);

49. Node paths - LCA /1/1/2 /1/2/1 /1/2/2 /1/1/1/2 /1/1/1/1 /2 /1/1/1 /1/2 /1/1 /1 Common substring starting from left

50. What do we do now…? • Setup a taxonomic name server (TNS) • Develop a phylogenetic genetic database linked to TNS, PubMed, GenBank, etc. • Develop easy ways to populate database (e.g., from TreeBASE, GenBank, journal databases) • Develop standard set of tree queries • Deploy