S1

1
1
1.5
1
S1
S2
S1
S2
S3
S4
0.5
1
1.5
1
S1
S2
S3
S4
0.75
0.5
1
2.75
1.5
1
S1
S2
S3
S4
S5
2
Score s(T,V) w1 w5 s(T,I) w1 w6 s(L,V) w2
w5 s(L,I) w2 w6 s(K,V) w3 w5 s(K,I) w3
w6 s(K,V) w4 w5 s(K,I) w4 w6 / 8

• PEEKSAVTAL
• GEEKAAVLAL
• K
• K

5. V 6. I
3
CLUSTALW

• Each sequence is weighted by how similar to
  others
• - overrepresentation of a subfamily
• - weight derived from the guide tree
• (in the example, weight for S5 and S4 2.75,
  1.9375)

• Details handling of gaps

• Problem situations
• similar only in smaller regions
• large insertion in a sequence
• repetitive elements in one sequence

4
Deriving the Sequence of Genome

• Need a rapid and accurate sequencing method

• Normal sequencing technique 700 b

• BAC 100-400 kb

• Random small fragments 2-10kb

• Assemble them

• http//seqcore.brcf.med.umich.edu/doc/educ/dnapr/s
  equencing.html

5
Genome alignment and comparison

• Sequencing - fast, available genomes

• Annotation not so fast
• - identify gene structure, function
• - cross species linking

• Comparative genomics
• -potential
• -coding and non-coding regions
• (e.g. human and mouse)
• -species-specific regions
• - selective pressure, evolution, rearrangement

6
Genome alignment and comparison - An example

• Mouse chromosome 16 and human genome
• (Mural et al, 2000, Science, 296, 1661-71)

7
Genome alignment

• Previous discussed alignment methods
• -most targets single gene
• -not accurate enough for genome scale
• -or computationally demanding

• Situation with genome comparisons
• rearrangements, repeats,

8
Methods in Genome Alignment gt1998

• DIALIGN Diagonal Alignment

• ASSIRC Accelerated Search for Similarity
  Regions in Chromosomes

• DBA DNA block aligner

• MUMmer - Maximal Unique Match (er)

• PipMaker percent Identity Plot Maker

• GLASS Global alignment System

• WABA Wobble Aware Bulk Aligner

• LSH-ALL-PAIRS Locality Similarity Hashing in All
  Pairs

9
Suffix Tree

• A suffix tree for an m-character-string S
• Has exactly m leaves, numbered 1 to m
• An internal nodes has at least 2 children
• Each edge is labeled with a non-empty substring
• No two edges out of the same node have the labels
  beginning with the same character

• From root to leaf i, the concatenation of the
  edge-labels on the path is the suffix of S
  starting from position i.

10
An Example of a Suffix Tree
String atgtgtgtc
11
MUMmer
Delcher AL, 2002 Nucleic Acid Research Vol
30(11) Delcher AL, 1999 Nucleic Acid Research Vol
27(11)

• Maximum Unique Match
• Occurs once in genome A and once in genome B
• Cant be extended

• Difference between MUM and common subsequence

• Idea long enough MUMs are part of the alignment

12
MUMmer
Delcher AL, 2002 Nucleic Acid Research Vol 30(11)
Example A acat B acaa

• Find MUMs

• Build a suffix tree for A and B

• Find unique matches then maximum matches