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Chapter 8: Graph Algorithms July/23/2012 Name: Xuanyu Hu Professor: Elise de Doncker Slide 2 Outline Graphs Graphs and Genetics DNA Sequencing Shortest Superstring Problem Slide 3 Diagrams with collections of points connected by lines are examples of graphs. The points are called vertices and lines are called edges. 1: Graphs Slide 4 We denote a graph by G = G(V, E) and describe it by its set of vertices V and set of edges E. Slide 5 This upper picture shows two white and two black knights on a 3*3 chessboard. Can they move, using the usual chess knight's moves, to occupy the positions shown in the below picture? How to Use Graph: Knights Problem 1 Slide 6 This picture represents the chessboard as a set of nine points. Two points are connected by a line if moving from one point to another is a valid knight move. Slide 7 The upper picture represents the chessboard as a set of nine points. Two points are connected by a line if moving from one point to another is a valid knight move. Slide 8 An equivalent representation of the resulting diagram that reveals that knights move aroung a "cycle" formed by points 1,6,7,2,9,4,3, and 8. Slide 9 Every knight's move on the chessboard corresponds to moving to a neighboring point in the diagram, in either a clockwise or counterclockwise direction. Therefore, the white-white- black-black knight arrangement cannot be transformed into the alternating white-black-white- black arrangement. Slide 10 How to Use Graph: Knights Problem 2 This picture represents anohter chessboard obtained from a 4*4 chessboard by removing the four corner squares. Can a knight travel around this board, pass through each square exactly once, and return to the same square it started on? Slide 11 A rather complex graph with twelve vertices and sixteen edges revealing all possible knight moves. Slide 12 Rearranging the vertices reveals the cycle that describes the correct sequence of moves. Slide 13 Connected and Disconnected A graph is called connected if all pairs of vertices can be connected by a path, which is a continuous sequence of edges, where each successive edge begins where the previous one left off. Graphs that are not connected are disconnected. Slide 14 Cycles Paths that start and end at the same vertex are referred to as cycles. For example, the paths(3-2-10-11-3), and paths(3-2-8-6- 12-7-5-11-3) are cycles. Slide 15 The Bridge Obsession Problem Bridges of Knigsberg Find a tour crossing every bridge just once Leonhard Euler, 1735 Slide 16 Eulerian Cycle Problem Find a cycle that visits every edge exactly once. Graph theory was born when Leonhard Euler solved the famous Knigsberg Bridge problem. More complicated Knigsberg Slide 17 Hamiltonian Cycle Problem Can you travel from any one of the vertices in this graph, visit every other vertex exactly once, and end up at the original vertex? Game invented by Sir William Hamilton in 1857 Slide 18 Trees Arthur Cayley studied chemical structures of hydrocarbons in the mid-1800s Structures of this type of hydrocarbon are examples of trees, which are simply connected graphs with no cycles. Slide 19 Every tree has at least one vertex with degree 1, called leaf. Every tree on n vertices has n-1 edges, regardless of the structure of the tree. Slide 20 Every tree has a leaf, we can remove it and its attached edge. We keep this up until we are left with a graph with a single vertex and no edges. Slide 21 2: Graphs and Genetics Benzers work Developed deletion mapping Proved linearity of the gene Demonstrated internal structure of the gene Seymour Benzer, 1950s Slide 22 Viruses Attack Bacteria Normally bacteriophage T4 kills bacteria However if T4 is mutated (e.g., an important gene is deleted) it gets disable and looses an ability to kill bacteria Suppose the bacteria is infected with two different mutants each of which is disabled would the bacteria still survive? Amazingly, a pair of disable viruses can kill a bacteria even if each of them is disabled. How can it be explained? Slide 23 Benzers Experiment Idea: infect bacteria with pairs of mutant T4 bacteriophage (virus) Each T4 mutant has an unknown interval deleted from its genome If the two intervals overlap: T4 pair is missing part of its genome and is disabled bacteria survive If the two intervals do not overlap: T4 pair has its entire genome and is enabled bacteria die Slide 24 Benzers Experiment and Graphs Construct an interval graph: each T4 mutant is a vertex, place an edge between mutant pairs where bacteria survived (i.e., the deleted intervals in the pair of mutants overlap) Interval graph structure reveals whether DNA is linear or branched DNA Slide 25 Interval Graph: Linear Genes Slide 26 Interval Graph: Branched Genes Slide 27 Interval Graph: Comparison Linear genomeBranched genome Slide 28 3: DNA Sequencing: History Sanger method (1977): labeled ddNTPs terminate DNA copying at random points. Both methods generate labeled fragments of varying lengths that are further electrophoresed. Gilbert method (1977): chemical method to cleave DNA at specific points (G, G+A, T+C, C). Slide 29 Sanger Method: Generating Read 1.Start at primer (restriction site) 2.Grow DNA chain 3.Include ddNTPs 4.Stops reaction at all possible points 5.Separate products by length, using gel electrophoresis Slide 30 DNA Sequencing Shear DNA into millions of small fragments Read 500 700 nucleotides at a time from the small fragments (Sanger method) Slide 31 Fragment Assembly Computational Challenge: assemble individual short fragments (reads) into a single genomic sequence (superstring) Until late 1990s the shotgun fragment assembly of human genome was viewed as intractable problem Slide 32 4: Shortest Superstring Problem Problem: Given a set of strings, find a shortest string that contains all of them Input: Strings s 1, s 2,., s n Output: A string s that contains all strings s 1, s 2,., s n as substrings, such that the length of s is minimized Note: this formulation does not take into account sequencing errors Slide 33 Shortest Superstring Problem: Example Concatenating all eight strings results in a 24- letter superstring the shortest superstring contains only 10 letters. Slide 34 Conclusion and Qustions Graphs graphs, vertex(vertices), edges, connected, disconnected, cycles, trees, degree, leaf Graphs and Genetics DNA Sequencing Shortest Superstring Problem Slide 35 References 1.http://bix.ucsd.edu/bioalgorithms/slides.php 2. http://en.wikipedia.org/wiki/Graph_theory 3.http://simple.wikipedia.org/wiki/Genetics 4.http://seqcore.brcf.med.umich.edu/doc/educ/dna pr/sequencing.html 5.http://www.wiley.com/college/pratt/0471393878/s tudent/animations/dna_sequencing/index.html 6.http://math.mit.edu/~goemans/18434S06/superst ring-lele.pdf