Lévy–Prokhorov metric: Difference between revisions

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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>
 
==Algorithm==
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>
===Step 1: Reliability of an alignment edge===
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.
 
<math>\begin{align}
P(x_i \sim y_i|x,y) & \stackrel{def}{=} Pr[x_i \sim y_i \text{ in some a }|x,y] \\
& = \sum_{\text{alignment a with }x_i - y_i} Pr[a|x,y]\\
& = \sum_{\text{alignment a}} \mathbf{1}\{x_i - y_i \in a\} Pr[a|x,y]
\end{align}</math>
 
(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.)
 
===Step 2: Maximum expected accuracy===
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.  
 
Calculate expected accuracy of each sequence:
 
<math>\begin{align}
E_{Pr[a|x,y]}(acc(a^*,a)) & = \sum_{a}Pr[a|x,y]acc(a^*,a) \\
& = \frac{1}{min(|x|,|y|)} \cdot \sum_{a}\mathbf{1}\{x_i \sim y_i \in a\} Pr[a|x,y]\\
& = \frac{1}{min(|x|,|y|)} \cdot \sum_{x_i - y_i} P(x_i \sim y_j|x,y)
\end{align}</math>
 
This yields a maximum expected accuracy (MEA) alignment:
 
<math>
E(x,y) = \arg\max_{a^*} \; E_{Pr[a|x,y]}(acc(a^*,a))
</math>
 
===Step 3: Probabilistic Consistency Transformation===
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:
 
<math>
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)
</math>
 
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.
 
== See also ==
* [[Sequence alignment software]]
* [[Clustal]]
* [[MUSCLE (alignment software)|MUSCLE]]
* [[AMAP]]
* [[T-Coffee]]
* [[Probalign]]
* [[ProbConsRNA]] &mdash; for [[nucleotide]] sequences
 
==References==
{{Reflist}}
 
==External links==
*{{Official website|http://probcons.stanford.edu/}}
 
[[Category:Bioinformatics]]
[[Category:Computational phylogenetics]]

Revision as of 20:22, 6 May 2013

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.[1]

Algorithm

The following describes the basic outline of the ProbCons algorithm. [2]

Step 1: Reliability of an alignment edge

For every pair of sequences compute the probability that letters xi and yi are paired in a* an alignment that is generated by the model.

P(xiyi|x,y)=defPr[xiyi in some a |x,y]=alignment a with xiyiPr[a|x,y]=alignment a1{xiyia}Pr[a|x,y]

(Where 1{xiyia} is equal to 1 if xi and yi are in the alignment and 0 otherwise.)

Step 2: Maximum expected accuracy

The accuracy of an alignment a* with respect to another alignment a is defined as the number of common aligned pairs divided by the length of the shorter sequence.

Calculate expected accuracy of each sequence:

EPr[a|x,y](acc(a*,a))=aPr[a|x,y]acc(a*,a)=1min(|x|,|y|)a1{xiyia}Pr[a|x,y]=1min(|x|,|y|)xiyiP(xiyj|x,y)

This yields a maximum expected accuracy (MEA) alignment:

E(x,y)=argmaxa*EPr[a|x,y](acc(a*,a))

Step 3: Probabilistic Consistency Transformation

All pairs of sequences x,y from the set of all sequences 𝒮 are now re-estimated using all intermediate sequences z:

P(xiyi|x,y)=1|𝒮|z1k|z|P(xizi|x,z)P(ziyi|z,y)

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.

See also

References

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