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A Report onA Computational Method to select Optimal Nucleotide Position for Site-
specific Mutagenesis to downregulate overexpression in Myc gene
Submitted byMustafa Safdari
2005P7PS015
For Partial Fulfillment ofBITS GC 331: Computer Project
Under the guidance and supervision ofProf. S. K. Ray
Biological Sciences DepartmentBITS, Pilani – Goa Campus
1st Semester 2008 – 2009
A BRIEF SUMMARY ABOUT THE PROJECT Computational Genomics based
project
Study of cancer causing effects in genes
Physicochemical properties of genes
Characterization of genes based on these properties
Use of this Characterization
Site-specific Mutagenesis
Drawbacks with current state-of-the-art
Project Aim
• Selection of parameters
• Development of methodology
• Simulation and analysis of results
Conclusions
1. Characterize both gene sequences2. Perform Sensitivity Operation on both resulting characterized sequences.3. Calculate the resultant centroids of the two sequences. If the centroids do
not differ considerably, then go to step 2 and perform sensitivity operation with a higher sensitivity order.
4. Calculate the distance between the 2 centroids, naming it DISTANCE.
The next sequence of steps is different, depending upon the type of resultant sought:
• Centroid: No further steps are required.• Cross Product: considering each nucleotide triplet as a codon vector,
find out the codon vectors of both the sequences with their centroids as their reference origin.
a) Convert each of these vectors into unit vectors.b)Perform cross product of all these vectors, taking unit vector at each
stage.c) Calculate the distance between the two resultants, naming it
DISTANCE1 5. Consider each codon in the mutated sequence one at a time, from the
beginning to the end. Create a newly modified sequence, which is a copy of the mutated sequence, except for the difference of this one codon where we substitute it with one of its degenerate codon. Perform the same steps 1 through 4 with the 2 sequences as the original normal and the newly modified sequence. Calculate the distance between the original normal sequence and this newly modified sequence naming it DISTANCEkj.
6. From the list of all the DISTANCEkj obtained, select the option with the least DISTANCEkj. This is the solution to the problem which brings the newly modified gene closest to the original normal gene in terms of functionality.
The codons in the sequence are represented as points are distributed in the 3-D space.
This is the centroid of this mutated gene sequence of codons
This is the centroid or the point depicting the characteristic value of the mutated sequence.
This is the centroid or the point depicting the characteristic value of the original normal sequence.
This region of green dots represents possible feasible solutions with characteristic points nearer to the original normal centroid than the mutated one.
This region of black dots represents possible feasible solutions with characteristic points farther to the original normal centroid than the mutated one.