ProbCons is an open source probabilistic consistency-based multiple alignment of amino acid sequences. It is an efficient protein multiple sequence alignment program, which has demonstrated a statistically significant improvement in accuracy compared to several leading alignment tools.
The following describes the basic outline of the ProbCons algorithm.
Step 1: Reliability of an alignment edge
For every pair of sequences compute the probability that letters and are paired in an alignment that is generated by the model.
(Where is equal to 1 if and are in the alignment and 0 otherwise.)
Step 2: Maximum expected accuracy
The accuracy of an alignment with respect to another alignment is defined as the number of common aligned pairs divided by the length of the shorter sequence.
Calculate expected accuracy of each sequence:
This yields a maximum expected accuracy (MEA) alignment:
Step 3: Probabilistic Consistency Transformation
All pairs of sequences x,y from the set of all sequences are now re-estimated using all intermediate sequences z:
This step can be iterated.
Step 4: Computation of guide tree
Construct a guide tree by hierarchical clustering using MEA score as sequence similarity score. Cluster similarity is defined using weighted average over pairwise sequence similarity.
Step 5: Compute MSA
Finally compute the MSA using progressive alignment or iterative alignment.
- Do CB, Mahabhashyam MS, Brudno M, Batzoglou S (2005). "PROBCONS: Probabilistic Consistency-based Multiple Sequence Alignment". Genome Research. 15 (2): 330–340. doi:10.1101/gr.2821705. PMC . PMID 15687296.
- Roshan, Usman (2014-01-01). Russell, David J, ed. Multiple Sequence Alignment Methods. Methods in Molecular Biology. Humana Press. pp. 147–153. doi:10.1007/978-1-62703-646-7_9. ISBN 9781627036450.
- Lecture "Bioinformatics II" at University of Freiburg