3 ms·

Sort of; though there are more complications. First, you have to deal with sequencing noise, which can be as high as 1%.. Thus you need many reads to get cons

by skosuri 15y ago

Sort of; though there are more complications. First, you have to deal with sequencing noise, which can be as high as 1%.. Thus you need many reads to get consensus even for any individual base. Second, you have to deal with the fact that a human genome has two copies of any individual chromosome, so you have to get enough reads to tell if your mutations are diploid or haploid for instance. Third, the human genome is repetitive, so there are many mapping errors. This is dealt with by having high coverage and usually by having different size jumps between paired sequencing reads (e.g., read 100bp on each end of a 200bp, 2000bp, and 10,000bp parts of the genome) to help algorithms stitch together the proper sequence.

tosseraccount 15y ago
There's even more complications to complicate the complications ... "you need many reads to get consensus even for any individual base" Not necessarily. If you know that the minor allele frequency it close to 50% in related populations and you only have a few reads, say 6, and three are minor allele non reference and three are "major" allele reference (and the quality is good and there's otherwise low regional noise), then it's a good bet it's HETEROZYGOUS. You don't necessarily need a lot of reads. "second, you have to deal with the fact that a human genome has two copies of any individual chromosome" Well. Sort of. Men only have one Y chromosome and one X chromosome for instance, women have zero Y's. (a nitpick, granted). Disease sample often have 0,1 and 3 or more copies of a genomic area.
- epistasis 15y ago
  That works if you're only performing a few such tests. But if you have an extremely accurate test, say 99.999% correct, and you apply it at 3 billion base pairs, then you're still going to have tens of thousands of incorrect calls, and no way to distinguish the good calls from the bad calls, without more data.

by skosuri 15y ago

tosseraccount 15y ago

There's even more complications to complicate the complications ... "you need many reads to get consensus even for any individual base" Not necessarily. If you know that the minor allele frequency it close to 50% in related populations and you only have a few reads, say 6, and three are minor allele non reference and three are "major" allele reference (and the quality is good and there's otherwise low regional noise), then it's a good bet it's HETEROZYGOUS. You don't necessarily need a lot of reads. "second, you have to deal with the fact that a human genome has two copies of any individual chromosome" Well. Sort of. Men only have one Y chromosome and one X chromosome for instance, women have zero Y's. (a nitpick, granted). Disease sample often have 0,1 and 3 or more copies of a genomic area.

epistasis 15y ago
That works if you're only performing a few such tests. But if you have an extremely accurate test, say 99.999% correct, and you apply it at 3 billion base pairs, then you're still going to have tens of thousands of incorrect calls, and no way to distinguish the good calls from the bad calls, without more data.