Seqanswers Leaderboard Ad

Collapse
X
 
  • Filter
  • Time
  • Show
Clear All
new posts
  • shyam_la
    Member
    • Mar 2012
    • 97

    Query on NonSilent and Silent mutations..

    What is the ratio of non-silent to silent mutations resulting from single nucleotide substitutions that can be expected, if every base is equally mutable and there is no selection pressure?

    Hope the question is clearly framed.

    I am asking so that I can comment on whether my dataset deviates from this hypothetical ratio and hence an idea of how much "Selection" really occurred.
  • BAMseek
    Senior Member
    • Apr 2011
    • 124

    #2
    I wrote some code that basically goes through all 64 possible nucleotide triplets, looks at every possible 1-base substitution (9 possibilities each), and checks if that substitution changes the amino acid.

    The code for this is available at https://gist.github.com/4162316

    I get 576 total substitutions (64*9). 138 are silent and 438 are nonsilent. This would be a ratio of silent:nonsilent = 138:438, which is approx. 1:3.17

    Does that make sense? This was done pre-coffee, so let me know if you find some issues.

    Justin

    Comment

    • HESmith
      Senior Member
      • Oct 2009
      • 512

      #3
      Shyam La,

      You'll also need to factor in the frequencies of the different types of mutations (e.g., transitions vs transversions) produced by your mutagen, as most exhibit significant biases.

      Comment

      • shyam_la
        Member
        • Mar 2012
        • 97

        #4
        Justin,

        That is exactly what I wanted to know; mutate each codon and get the result. Thank you!
        But I'm guessing 1:3.17 is not a biologically meaningful ratio because typically cancers (which is what I am dealing with) have something like 1:2 and they also are subjected to some amount of selection pressure which means we would expect a ratio bigger than 1:3.17 (more non silent than silent).

        HESmith's idea that mutagen biases have to be included is a valid argument, I guess..


        Originally posted by BAMseek View Post
        I wrote some code that basically goes through all 64 possible nucleotide triplets, looks at every possible 1-base substitution (9 possibilities each), and checks if that substitution changes the amino acid.

        The code for this is available at https://gist.github.com/4162316

        I get 576 total substitutions (64*9). 138 are silent and 438 are nonsilent. This would be a ratio of silent:nonsilent = 138:438, which is approx. 1:3.17

        Does that make sense? This was done pre-coffee, so let me know if you find some issues.

        Justin

        Comment

        • BAMseek
          Senior Member
          • Apr 2011
          • 124

          #5
          Yeah, that model might be too simplistic, but I guess it gives a baseline considering all things equal.

          From what I've seen in the literature, the transition to transversion ratio is around 2-2.1 for the entire genome, and around 2.8-3.0 within the exome.

          A more realistic approach might be to take a bunch of normal human exomes and calculate the silent to non silent mutations. Or, instead of trying to find silent/non-silent, maybe calculate the transitions to transversions in your dataset and see if that agrees with the numbers found in literature.

          Justin

          Comment

          • mlodato
            Junior Member
            • Aug 2013
            • 8

            #6
            Perhaps this is useless since the thread is so old, but I have been thinking about this as well and came across this paper:

            PMID:16783027

            which seems to model SNS as well as regional biases to get expected numbers of missense vs nonsense mutations.

            Comment

            Latest Articles

            Collapse

            • seqadmin
              New Genomics Tools and Methods Shared at AGBT 2025
              by seqadmin


              This year’s Advances in Genome Biology and Technology (AGBT) General Meeting commemorated the 25th anniversary of the event at its original venue on Marco Island, Florida. While this year’s event didn’t include high-profile musical performances, the industry announcements and cutting-edge research still drew the attention of leading scientists.

              The Headliner
              The biggest announcement was Roche stepping back into the sequencing platform market. In the years since...
              03-03-2025, 01:39 PM
            • seqadmin
              Investigating the Gut Microbiome Through Diet and Spatial Biology
              by seqadmin




              The human gut contains trillions of microorganisms that impact digestion, immune functions, and overall health1. Despite major breakthroughs, we’re only beginning to understand the full extent of the microbiome’s influence on health and disease. Advances in next-generation sequencing and spatial biology have opened new windows into this complex environment, yet many questions remain. This article highlights two recent studies exploring how diet influences microbial...
              02-24-2025, 06:31 AM

            ad_right_rmr

            Collapse

            News

            Collapse

            Topics Statistics Last Post
            Started by seqadmin, 03-20-2025, 05:03 AM
            0 responses
            17 views
            0 reactions
            Last Post seqadmin  
            Started by seqadmin, 03-19-2025, 07:27 AM
            0 responses
            18 views
            0 reactions
            Last Post seqadmin  
            Started by seqadmin, 03-18-2025, 12:50 PM
            0 responses
            19 views
            0 reactions
            Last Post seqadmin  
            Started by seqadmin, 03-03-2025, 01:15 PM
            0 responses
            186 views
            0 reactions
            Last Post seqadmin  
            Working...