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An example: finding cpg islands

This example is taken from the excellent textbook Biological Sequence Analysis: probabilistic models of proteins and nucleic acids by Durbin, Eddy, Krogh and Mitchison. CpG islands are regions of the genome with a higher than normal percentage of C and G bases adjacent to each other. The usual percentage of adjacent CG bases in the genome is about 1%, but in CpG islands that percentage is over 6%. The reason that C followed by G is relatively rare in The "p" in "CpG" refers to the phosphodiester bond between the cytosine and the guanine, and serves to distinguish it from the C and G pairing on the double stranded DNA helix. CpG islands are bioogically intersting because they are in or near 40% of the promoters in mammalian genes and 70% in human promoter genes. CpG islands vary in length between 300 and 3000 basepairs. Thus fixed-length consensus sequence based approaches do not work well for detecting them. Effective identification of of CpG islands can aid in localizing genes in eukaryotes. CpG island detection also serves as an excellent problem to illustrate the power of Markov models.

We will consider two problems.

  • Given a short DNA sequence, does it come from a CpG island or not?
  • Given a long DNA sequence, find all the CpG islands on it, if any.

Generative models of biological sequences

We will construct generative models of CpG islands. A generative model produces strings, and the model parameters are tuned to reflect the characteristics of CpG islands.

Generative models for cpg island detection

The simplest probabilistic generative DNA sequence model associates a probability with the occurrence of each base: P(A), P(C), P(G) and P(T) such that these probabilities all sum to 1. For H. influenzae, these probabilities are P(A) = 0.3, P(C) = 0.2, P(G) = 0.2, and P(T) = 0.3. To generate a sequence based on this model, we first choose the length L of the sequence that we wish to construct. Then we draw bases for each position based on the discrete distribution above, as shown in the code fragement below.

i = 1; while i less-than-or-equal-to L doS[i] = a base drawn from the discrete probability distribution [0.3,0.2,0.2,0.3](for A,C,G,T) i = i+1end

This model does not capture interdependencies between bases. It assumes that the choice of base in each position of the generated sequence is independent of the bases surrounding it. A more complex model of DNA sequences can be constructed using the theory of Markov chains. In Markov chains, the probability of observing a base at a given position in a sequence is conditioned on the bases preceding it. Thus, Markov chains can model local correlations among the nucleotides. A Markov chain of order 1 assumes that the probability of a base at position i is dependent only on the base at position i - 1. A first order Markov chain can be specified by a probability matrix as shown below.

A first order markov model for generating dna sequences
A 0.6 0.2 0.1 0.1
C 0.1 0.1 0.8 0.0
G 0.2 0.2 0.3 0.3
T 0.1 0.8 0.0 0.1

Questions & Answers

do you think it's worthwhile in the long term to study the effects and possibilities of nanotechnology on viral treatment?
Damian Reply
absolutely yes
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Do somebody tell me a best nano engineering book for beginners?
s. Reply
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Devang Reply
are you nano engineer ?
fullerene is a bucky ball aka Carbon 60 molecule. It was name by the architect Fuller. He design the geodesic dome. it resembles a soccer ball.
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That is a great question Damian. best way to answer that question is to Google it. there are hundreds of applications for buck minister fullerenes, from medical to aerospace. you can also find plenty of research papers that will give you great detail on the potential applications of fullerenes.
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s. Reply
Yeah, it is a pain to say the least. You basically have to heat the substarte up to around 1000 degrees celcius then pass phosphene gas over top of it, which is explosive and toxic by the way, under very low pressure.
Do you know which machine is used to that process?
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s. Reply
of graphene you mean?
or in general
in general
Graphene has a hexagonal structure
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what is biological synthesis of nanoparticles
Sanket Reply
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Yes, Nanotechnology has a very fast field of applications and their is always something new to do with it...
Himanshu Reply
good afternoon madam
what is system testing
what is the application of nanotechnology?
In this morden time nanotechnology used in many field . 1-Electronics-manufacturad IC ,RAM,MRAM,solar panel etc 2-Helth and Medical-Nanomedicine,Drug Dilivery for cancer treatment etc 3- Atomobile -MEMS, Coating on car etc. and may other field for details you can check at Google
anybody can imagine what will be happen after 100 years from now in nano tech world
after 100 year this will be not nanotechnology maybe this technology name will be change . maybe aftet 100 year . we work on electron lable practically about its properties and behaviour by the different instruments
name doesn't matter , whatever it will be change... I'm taking about effect on circumstances of the microscopic world
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silver nanoparticles could handle the job?
not now but maybe in future only AgNP maybe any other nanomaterials
I'm interested in Nanotube
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Source:  OpenStax, Statistical machine learning for computational biology. OpenStax CNX. Oct 14, 2007 Download for free at http://cnx.org/content/col10455/1.2
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