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.
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 x i {\displaystyle x_{i}} and y i {\displaystyle y_{i}} are paired in a ∗ {\displaystyle a^{*}} an alignment that is generated by the model.
P ( x i ∼ y i | x , y ) = d e f Pr [ x i ∼ y i in some a | x , y ] = ∑ alignment a with x i − y i Pr [ a | x , y ] = ∑ alignment a 1 { x i − y i ∈ a } Pr [ a | x , y ] {\displaystyle {\begin{aligned}P(x_{i}\sim y_{i}|x,y)\ {\overset {\underset {\mathrm {def} }{}}{=}}&\ \Pr[x_{i}\sim y_{i}{\text{ in some }}a|x,y]\\[8pt]=&\ \sum _{{\text{alignment }}a \atop {{\text{with }}x_{i}-y_{i}}}\Pr[a|x,y]\\[2pt]=&\ \sum _{{\text{alignment }}a}\mathbf {1} \{x_{i}-y_{i}\in a\}\Pr[a|x,y]\end{aligned}}}
(Where 1 { x i ∼ y i ∈ a } {\displaystyle \mathbf {1} \{x_{i}\sim y_{i}\in a\}} is equal to 1 if x i {\displaystyle x_{i}} and y i {\displaystyle y_{i}} are in the alignment and 0 otherwise.)
Step 2: Maximum expected accuracy The accuracy of an alignment a ∗ {\displaystyle a^{*}} with respect to another alignment a {\displaystyle a} is defined as the number of common aligned pairs divided by the length of the shorter sequence. Calculate expected accuracy of each sequence:
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