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| '''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.<ref>{{cite journal |doi=10.1101/gr.2821705 |author=Do CB, Mahabhashyam MSP, Brudno M, Batzoglou S |year=2005 |title=PROBCONS: Probabilistic Consistency-based Multiple Sequence Alignment |journal=Genome Research |volume=15 |issue=2 |pages=330–340 |pmid=15687296 |pmc=546535}}</ref>
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| ==Algorithm==
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| The following describes the basic outline of the ProbCons algorithm. <ref>Lecture "Bioinformatics II" at University of Freiburg [http://www.bioinf.uni-freiburg.de//Lehre/Courses/2011_WS/V_BioinfoII/slides_probcons.pdf]</ref>
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| ===Step 1: Reliability of an alignment edge===
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| For every pair of sequences compute the probability that letters <math>x_i</math> and <math>y_i</math> are paired in <math>a^*</math> an alignment that is generated by the model.
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| <math>\begin{align}
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| P(x_i \sim y_i|x,y) & \stackrel{def}{=} Pr[x_i \sim y_i \text{ in some a }|x,y] \\
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| & = \sum_{\text{alignment a with }x_i - y_i} Pr[a|x,y]\\
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| & = \sum_{\text{alignment a}} \mathbf{1}\{x_i - y_i \in a\} Pr[a|x,y]
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| \end{align}</math>
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| (Where <math>\mathbf{1}\{x_i \sim y_i \in a\}</math> is equal to 1 if <math>x_i</math> and <math>y_i</math> are in the alignment and 0 otherwise.)
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| ===Step 2: Maximum expected accuracy===
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| The accuracy of an alignment <math>a^*</math> with respect to another alignment <math>a</math> is defined as the number of common aligned pairs divided by the length of the shorter sequence.
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| Calculate expected accuracy of each sequence:
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| <math>\begin{align}
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| E_{Pr[a|x,y]}(acc(a^*,a)) & = \sum_{a}Pr[a|x,y]acc(a^*,a) \\
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| & = \frac{1}{min(|x|,|y|)} \cdot \sum_{a}\mathbf{1}\{x_i \sim y_i \in a\} Pr[a|x,y]\\
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| & = \frac{1}{min(|x|,|y|)} \cdot \sum_{x_i - y_i} P(x_i \sim y_j|x,y)
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| \end{align}</math>
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| This yields a maximum expected accuracy (MEA) alignment:
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| <math>
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| E(x,y) = \arg\max_{a^*} \; E_{Pr[a|x,y]}(acc(a^*,a))
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| </math>
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| ===Step 3: Probabilistic Consistency Transformation===
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| All pairs of sequences x,y from the set of all sequences <math>\mathcal{S}</math> are now re-estimated using all intermediate sequences z:
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| <math>
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| P'(x_i - y_i|x,y) = \frac{1}{|\mathcal{S}|} \sum_{z} \sum_{1 \leq k \leq |z|} P(x_i \sim z_i|x,z) \cdot P(z_i \sim y_i|z,y)
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| </math>
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| This step can be iterated.
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| ===Step 4: Computation of guide tree===
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| 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.
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| ===Step 5: Compute MSA===
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| Finally compute the MSA using progressive alignment or iterative alignment.
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| == See also ==
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| * [[Sequence alignment software]]
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| * [[Clustal]]
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| * [[MUSCLE (alignment software)|MUSCLE]]
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| * [[AMAP]]
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| * [[T-Coffee]]
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| * [[Probalign]]
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| * [[ProbConsRNA]] — for [[nucleotide]] sequences
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| ==References==
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| {{Reflist}}
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| ==External links==
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| *{{Official website|http://probcons.stanford.edu/}}
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| [[Category:Bioinformatics]]
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| [[Category:Computational phylogenetics]]
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Hello! Let me begin by stating my title - Ron Stephenson. Playing croquet is something I will by no means give up. My house is now in Kansas. I am a cashier and I'll be promoted soon.
Feel free to surf to my web site :: http://phoenixbiofuel.com/