Transcript Sequence Alignment

Bioinformatics
Lecture 2
By: Dr. Mehdi Mansouri
[email protected]
Mehr 1395
Sequence Alignment
• Sequence comparison lies at the heart of bioinformatics
analysis.
• It is an important first step toward structural and functional
analysis of newly determined sequences.
Driving force of evolution
• Mutation
• Natural Selection
EVOLUTIONARY BASIS
• Biologists define evolution as genetic change in a population
across generations.
• Over time, this process of genetic change can give rise to new
genes, new traits and new species, all brought about through
changes in the genetic code or DNA.
Structural variations
 Deletions
 Insertions
 Inversions
 Tandem duplications
 Translocations
 And more complex rearrangements
Sequence Homology VS Sequence Similarity
• When two sequences are descended from a common
evolutionary origin, they are said to have a homologous
relationship
• Sequence similarity is percentage of aligned residues that are
similar in physiochemical properties such as size, charge, and
hydrophobicity.
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Paralogue
A homologue which arose through gene duplication in the same
species/chromosome
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Orthologue
A homologue which arose through speciation (found in different species)
Sequence Similarity VS Sequence Identity
• Sequence similarity and sequence identity are synonymous for
nucleotide sequences.
Sequence alignment
Global Alignment and Local Alignment
• In global alignment, two sequences to be aligned are assumed
to be generally similar over their entire length
• Local alignment, does not assume that the two sequences in
question have similarity over the entire length.
Alignment Algorithms
• Dot matrix method
• Dynamic programming method
• Word method.
Dot matrix method
Dynamic programming method
Gap Penalties
• Performing optimal alignment between sequences often
involves applying gaps that represent insertions and deletions.
Database Similarity Searching
• A main application of pairwise alignment is retrieving
biological sequences in databases based on similarity
• Sensivity
• Specificity
• speed
• BLAST
• FASTA
• Both BLAST and FASTA use a heuristic word method
BASIC LOCAL ALIGNMENT SEARCH TOOL (BLAST)
• The BLAST program was developed by Stephen Altschul of
NCBI in 1990
BLAST variants
https://blast.ncbi.nlm.nih.gov
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BLASTN
BLASTP
BLASTX
TBLASTN
TBLASTX