I'm mostly very confident that the ideas I wrote in my last post were correct, but the postdoc still has doubts, and each time I try to explain my position to him I come away with my own little niggling doubts. So here's a different perspective.
This time I'll start from the biology of DNA uptake and the consequent accumulation of preferred sequences in the genome.
Our computer simulation model showed that the sequences that accumulate in the genome have the same properties as the bias of the uptake machinery. The model could consider only the base biases of each position individually (there were no between-position interaction effects), but I think we can safely expect that any interaction effects in the uptake bias will also be seen in the sequences that accumulate in the genome.
When we, as researchers, examine the sequence patterns of the preferred-uptake sequences and the overrepresented-in-the-genome sequences, we first compare the single-position pattern and then compare the interaction-effect pattern. Because the two sets of sequences are the same, we will find the same patterns.
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Now let's consider a real research situation, where we don't know anything about the underlying biology. We identify a set of sequences that are preferred by the uptake machinery, and another set that are overrepresented in the genome. We analyze each set, and find that the single-position patterns are different.
What can we infer about the underlying biology? We must conclude that the two sets of sequences have different properties, and thus that the sequences preferred by the uptake machinery are not the same as the sequences overrepresented in the genome. The differences must be due to post-uptake forces that alter the sequences accumulating in the genome.
We might go on to analyze the interaction effects in the uptake set of sequences and in the genomic set of sequences. These analyses may give us insights into the uptake process and the post-uptake forces, but they won't change the fact that the two sequence sets are different.
Clik here to view.
Image may be NSFW.
Clik here to view.
This time I'll start from the biology of DNA uptake and the consequent accumulation of preferred sequences in the genome.
When we, as researchers, examine the sequence patterns of the preferred-uptake sequences and the overrepresented-in-the-genome sequences, we first compare the single-position pattern and then compare the interaction-effect pattern. Because the two sets of sequences are the same, we will find the same patterns.
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Now let's consider a real research situation, where we don't know anything about the underlying biology. We identify a set of sequences that are preferred by the uptake machinery, and another set that are overrepresented in the genome. We analyze each set, and find that the single-position patterns are different.
What can we infer about the underlying biology? We must conclude that the two sets of sequences have different properties, and thus that the sequences preferred by the uptake machinery are not the same as the sequences overrepresented in the genome. The differences must be due to post-uptake forces that alter the sequences accumulating in the genome.
We might go on to analyze the interaction effects in the uptake set of sequences and in the genomic set of sequences. These analyses may give us insights into the uptake process and the post-uptake forces, but they won't change the fact that the two sequence sets are different.
Image may be NSFW.
Clik here to view.
Image may be NSFW.
Clik here to view.
Image may be NSFW.
Clik here to view.
Image may be NSFW.
Clik here to view.
Image may be NSFW.
Clik here to view.
Image may be NSFW.
Clik here to view.
Image may be NSFW.
Clik here to view.
Image may be NSFW.Clik here to view.

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