8 ms·
As other commenters point out, this "analysis" is a joke. An E()-value of 282 says we would expect a match of this short sequence against a completely random l
by fastaguy88 5y ago
As other commenters point out, this "analysis" is a joke. An E()-value of 282 says we would expect a match of this short sequence against a completely random library of the same size 282 times. Even with BLASTp's parameter correction for short sequences, NO short sequence will generate a statistically significant score.
Let's try a more sensible approach. Let's see how often the sequence occurs in other databases. The author's 1/20^6 (1/64,000,000) probability calculation omits the fact that every database search considers many millions of possible alignments (a crude calculation would be 6 * the database length, or 6 * 1.6E7/20^6 ~ 10000E6/64E6 = 156 times by chance), and we're shown that in a 5,000,000 protein/1.6E7 residue database, 100% matches are seen several dozens of times, as expected.
How about other protein sets? Search the human protein set (19,000 proteins), there are no 6 amino acid 100% identical matches. The best matches are 100% of 5 residues, or 83% identity over 6 (with an E()-value of 22).
How many proteins do we need to search to find an exact full-length match? (we have dozens of matches in a 5,000,000 viral protein database. and none in 19,000). If you search all the NCBI landmark sequences (~500,000, non-redundant), there are 3 identical matches (E()-value: ~44) in Drosophila, Corn, and Strep. pneumoniae. So this sequence is not very special -- as the E()-value statistics indicate, it happens all the time by chance. (If it happens 3 times in a 500,000 sequence non-redundant database by chance, we would expect it to happen 30-100's of times in a 5,000,000 redundant viral database by chance, which is what we see.)
Six amino acid non-significant matches are evidence that properly done statistics are accurate, and pretty much nothing else.
- arisAlexis 5y agoIt's not only the numbers. 1 out of 282 with the one being Moderna is much more significant. The null hypothesis is important. It's not just the odds reporting. Anybody can pass by your door accidentally Less likely it is someone that threatened you last night. Same odds, different situations.
- fastaguy88 5y agoIt is not clear to me why it is much more significant (or how much more). There is confirmation bias here. There would be no "report" if Moderna had not been associated with the sequence. So how many other, perhaps longer, matches were there to other patented sequences with no connection to Moderna? If there were hundreds (which there probably were), it is much less clear what the significance of one of them being in a Moderna patent is, particularly if Moderna was trying to make an HIV vaccine, and the sequence is in HIV (which it is).