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Bioinformatics Chaper3

This document discusses key concepts in bioinformatics including biological databases, sequence comparisons, applications of sequence comparison, principles of evolution, homology, sequence alignment methods like dot plots and dynamic programming, scoring matrices, and BLAST search tools.

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Thư Trương
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11 views34 pages

Bioinformatics Chaper3

This document discusses key concepts in bioinformatics including biological databases, sequence comparisons, applications of sequence comparison, principles of evolution, homology, sequence alignment methods like dot plots and dynamic programming, scoring matrices, and BLAST search tools.

Uploaded by

Thư Trương
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as PDF, TXT or read online on Scribd
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Bioinformatics

Lecturer: Nam Vo
Email: [email protected]
2
Contents

 Biological databases

 Sequence comparisons and Sequence-Based


database searches
3 Applications of sequence
comparison
 Find common ancestors
 Analyze phylogenetic trees
 Annotations of new nucleotide and protein
sequences
 Construction of model structures for proteins
 Design and analysis of expression studies
 Others
4
Stranger???
5
Principles

 Nature acts conservatively – it does not develop a


new kind of biology for every life form but continuously
changes and adapts a proven general concept
 Novel functionalities do not appear because a new
gene has suddenly arisen but are developed and
modified during evolution
6
Convergent and divergent
evolution
7
Homology

• Homology is not a measure of similarity,


but rather signifies that sequences have a
shared evolutionary history and, therefore,
possess a common ancestral sequence
• Ortholog: Homologous proteins from
different species that possess the same
function
• Paralog: homologous proteins that have
different functions in the same species
8
9
Identity vs similarity

 Identity: ratio of the number of identical amino acids


or nucleotides in a sequence to the total number of
amino acids or nucleotides
 Similarity: calculated base on similarity matrices
(substitution or scoring matrices)
10
Sequence alignment

Principle: Add gaps to


sequences to obtain the
best alignment
(highest similarity/identity)
11
Protein sequence alignment
12
Scoring matrices

 Amino acid substitution matrices describe the


probability that amino acids will be exchanged in the
course of evolution

Aspartic acid  Glutamic acid


VS
Aspartic acid  Tryptophan
13
Scoring matrices
14
Dot - plot
15
Dot - plot
16
Dot - plot
17
Dot - plot

Sequence A
Sequence B
18
Dot - plot
Sequence A
Sequence B
19
Dot - plot
Sequence A
Sequence B
20
Dot - plot
Sequence A
Sequence B
21
Dot - plot

Sequence
1 2 A
Sequence A

2
22
Dot - plot
23
Dynamic programing
24
Dynamic programing
(Needleman and Wunsch)
 Match: +1
 Mismatch or Indel: −1
25
Global alignment

Local alignment
26
Local alignment

 Introduced by Smith and Waterman (1981)


 Identify protein domains and motifs
 Replace negative scores by a zero
 Trace back Start from highest score
 Trace back End when meet a zero
27
Affine gap

 Existing gap: penalty score for the first gap


 Extension gap: penalty score for new gap next to
existing gap
28
Multiple sequence
alignment
29
Multiple sequence alignment
30 http://www.ncbi.nlm.nih.gov/BLAST/

Heuristic method: making assessments to obtain almost exact results


31
32
33
Protein BLAST algorithms

• Position-Specific Iterated BLAST (PSI-BLAST)


• Pattern-Hit Initiated BLAST (PHI-BLAST)
• Domain Enhanced Lookup Time Accelerated
BLAST (DELTA-BLAST)
• Bl2seq (blast 2 sequences)
34 Take home lessons
 Sequence comparison applications
 Convergent and divergent evolution
 Homology, homologs, orthologs, paralogs
 Identity vs similarity
 Pairwise alignment
 Dot-plot
 Dynamic programing
 Word method
 Multiple sequence alignment
 Global alignment vs local alignment
 Linear gap vs affine gap
 BLAST tool

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