Python Programming for Biology: Bioinformatics and Beyond

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Pairwise sequence alignments

Contents

Sequence alignment

Sequence classification

Conservation analysis

Genetic trees

Protein structure prediction

Whether to align protein or DNA

Calculating an alignment score

Sequence identity

Substitutability

Calculating sequence similarity

Optimising pairwise alignment

Dynamic programming

Pairwise alignment with Python

Quick database searches

Using BLAST from Python

Sequence alignment

The  alignment  of  biological  sequences  is  probably  the  most  widely  used  operation  in

bioinformatics.  In  essence  sequences  are  aligned  so  that  we  can  determine  how  similar

they  are,  and  from  this  all  sorts  of  useful  information  can  come,  such  as  whether  two

sequences are related by evolution (they have a common ancestor) or whether they have a

similar  biological  function.  The  process  of  comparison  is  called  alignment  because  the

trickiest  part  of  the  process  is  to  say  which  bits  of  two  sequences  are  equivalent  to  one

another; how residues of the different sequences can be paired up. Usually when we align

sequences  we  seek  to  determine  the  best  alignment  out  of  the  vast  number  of  possible

comparisons by finding the combination of residue pairs, one from each sequence, which

gives the highest overall score for similarity.

Once a sequence alignment has been achieved, and assuming you trust the results, you

can treat the aligned regions as having a degree of equivalency. If the alignment is good

enough you might be able to say, for example, that two DNA sequences relate to the same

kind  of  gene,  despite  the  nucleotides  not  being  exactly  the  same.  It  should  always  be

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remembered,  however,  that  a  sequence  alignment  can  only  give  a  limited  amount  of

information about the underlying biology, but it is often an excellent starting point. Even

where  the  knowledge  gained  is  distinctly  incomplete,  a  sequence  alignment  is  quick  to

perform and often helpful to guide experiments. You might significantly narrow down the

number  of  possibilities  of  what  a  section  of  DNA  or  protein  could  be,  or  say  what  it

definitely is not, with one simple database search, i.e. doing alignments against a database

of  well-studied  sequences.  Sequence  alignments  are  also  done  in  a  laboratory  setting  to

guide procedures, for example to determine which part of a protein to investigate.