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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

Is there any normative that regulates the use of silver nanoparticles?
Damian Reply
what king of growth are you checking .?
What fields keep nano created devices from performing or assimulating ? Magnetic fields ? Are do they assimilate ?
Stoney Reply
why we need to study biomolecules, molecular biology in nanotechnology?
Adin Reply
yes I'm doing my masters in nanotechnology, we are being studying all these domains as well..
what school?
biomolecules are e building blocks of every organics and inorganic materials.
anyone know any internet site where one can find nanotechnology papers?
Damian Reply
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Introduction about quantum dots in nanotechnology
Praveena Reply
what does nano mean?
Anassong Reply
nano basically means 10^(-9). nanometer is a unit to measure length.
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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it is a goid question and i want to know the answer as well
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s. Reply
there is no specific books for beginners but there is book called principle of nanotechnology
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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.
what is the actual application of fullerenes nowadays?
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.
what is the Synthesis, properties,and applications of carbon nano chemistry
Abhijith Reply
Mostly, they use nano carbon for electronics and for materials to be strengthened.
is Bucky paper clear?
carbon nanotubes has various application in fuel cells membrane, current research on cancer drug,and in electronics MEMS and NEMS etc
so some one know about replacing silicon atom with phosphorous in semiconductors device?
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?
how to fabricate graphene ink ?
for screen printed electrodes ?
What is lattice structure?
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
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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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