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Genome analysis. Lecture 11: literature discussion. Papers. Consensus sequences improve PSI-BLAST through mimicking profile-profile alignments Dariusz Przybylski and Burkhard Rost Nucleic Acids Research 2007
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Genome analysis Lecture 11: literature discussion
Papers • Consensus sequences improve PSI-BLAST through mimicking profile-profile alignmentsDariusz Przybylski and Burkhard RostNucleic Acids Research 2007 • Heads or Tails: A Simple Reliability Check for Multiple Sequence AlisngmentsGiddy Landan and Dan GraurMolecular Biology and Evolution 2007
BLAST and PSI-BLAST • BLAST is a sequence-sequence method:Sequence (query) –Sequence (nr database) • PSI-BLAST is a profile-sequence method:RUN 1: just like normal BLASTRUN 2: Profile (query) –Sequence (nr database)
Accuracy vs. Speedthe usual dilemma … Sequence – Sequence Profile – Sequence Profile – Profile ACCURACY SPEED
Profile A C D . . Y Consensus sequences - 1 • “1-D semplification of the sequence profile” • Compromise between accuracy and speed
Consensus sequences - 2 • How can we display consensus sequences? • Replace the complete sequence by the consensus sequence (100%) • Replace only local parts by consensus segments(top 50% & low 50%) • Tests on: • Sequence – Consensus • Consensus – Consensus • Profile – Consensus
Evaluation of results • Ability to identify functionally related proteins • Correctly align them based on structural alignments • Function is more conserved than Structure
Functional evaluation: SCOP classes folds superfamilies families
Structural evaluation: 3D model quality • Making the model: simply copy coordinates • Test model quality through LGA superposition (query model with query structure) • ‘Golden standard’: structural alignment of known structure of query & template with MAMMOTH MAGFWIL MLGKSLL query template
Final sets for alignment test • Set 1: most related, non-trivial pairs(no. = 1647) • Set 2: more difficult, most diverged(no. = 5551)
There are quite some multiple alignment methods .... PRALINE ... but what about accuracy?
Benchmarking: usual on structural alignments. • There are several alignment benchmarks, such as BAliBASE, HOMSTRAD or SABMARK • But they can only tell us the alignment quality on their predefined sets • Alignment methods need to define quality and consistency criteria.