ProbCons

In bioinformatics and proteomics, ProbCons is an open source software for probabilistic consistency-based multiple alignment of amino acid sequences. It is one of the most efficient protein multiple sequence alignment programs, since it has repeatedly demonstrated a statistically significant advantage in accuracy over similar tools, including Clustal and MAFFT.

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Algorithm

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.

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 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.