May 29, 2011

CpG Islands (1) - Problem Motivation & Definitions

This semester I'm attending the course Processing of Sequences and Methods and Algorithm in Computational Biology (basically DNA and proteins). One of the focus of it is the use of the Hidden Markov Models to solve many of it's problems. One well studied problems is how to find codifying sequences (snippets that can be translated into proteins) in a given sequence of DNA, which has both codifying and non codifying regions. One of the most used techniques is called CpG islands.

In a random DNA sequence we have a lower frequency of two ((G)uanine and (C)ytosine) than the other two nucleotide types ((A)denine and (T)hymine) due to a phenomenon called DNA methylation. Due to this methylation, it's more probable to occur a deletion of a C and G nucleotides than with A or T

DNA double helix structure


In the species evolution, occurs that genes which are essential for it's survival cannot mutate much, otherwise the organism can't live and reproduce to transmit it's gene to their descendants. Because of this, is very unlikely that even with lots of generations, those genes doesn't suffer much alteration. It's important to notice that non codifying regions can mutate without affecting the organism because it doesn't affect a vital part of the genetic code.

With these two facts in hand we can see that mutation of the DNA can occur more frequently on non codifying regions. As the methylation of C is a very common mutation cause, we can observe that non codifying regions will have less C and G due to the methylation which it doesn't interfere (much) in the organism. The opposite occurs with codifying regions because it has less frequent mutations.
CpG island around an important human DNA regulation site

With this information in our hands we can use it to discover regions which are likely to be a codifying region. The sites which contains greater concentrations of C-phosphate-G (called CpG islands) are a strong indicator that it hasn't suffered much mutations through the generations. So it's very probable to be an area of interest for biologists. I'll describe in the next posts how can we identify these CpG using HMM and the ghmm python library.

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