ends 1/ For the human genome project, Pres Clinton in his last year had a press conference with the two teams (Private Ventner vs Public NIH) present announcing its "completion". (Or maybe Bush in his first year, I don't remember for sure.) In any case, all the genome scientists knew that it wasn't really "complete", just the first phase, the easier stuff. Large chunks of the sequencing could be aligned onto the (classical) genetic map, but they could not rule out unknown gaps between the known sequenced chunks. That came later, perhaps, but I'm not really sure if there are still some gaps remaining even >20yrs later. I haven't followed it that closely.
ends 2/ The technical issue with the resistant portion involves "repetitive" DNA. The concept overlaps with what is sometimes (falsely?) referred to as "junk" DNA.
Assembly programs like Megahit would have a problem with sequential repeats if the k-mers are too small. Even large k-mers (maybe 81nt), could not deal with a tract of hundreds of small repeats.
Assembly programs could even have a problem with well separated repeats. Well separated repeats within the SARS-CoV-2 genome could present problems for Megahit. I mentioned something about "subgenomic RNA junctions" in part "6/". These "junctions" are generated by the repeats, which are subject to "cut and paste" operations (actually, more like, "jump from one repeat to the next"). For the human genome, "cut and paste" operations result in birth defects (eg Down's syndrome) and cancers.
ends 3/ The problem with failure to "complete" (in the absolute sense) the human genome probably could not be solved before very long read technology such as Nanopore and Pacific Biosystems came about.
None of this directly addresses Covid19 ends, except as context. First lesson from the human genome project: "Take your victory where you can" (99% glass full), and "keep plugging away at the rest" (1% glass empty).
Second lesson from the HGP: "Failure to resolve gaps do not invalidate the concept of the human genome", nor does it mean that humans don't exist.
ends 4/ Apart from the variable length of the 3' PolyA tract, which is real and may have some biological meaning, you are complaining about high sequence variation just within the polyA tract, and just within the 5' cap. I don't know if this variation is real and has biological meaning for individuals within a "swarm", or if it is a technical issue (sequencing errors, not real variation), or a combination of both.
Recall that the Wuhan sequencing project had 3 phases, the last being a very special technique for the ends. I have not yet read about this technique. I don't know if these special end reads are included in your dataset, nor do I know if they would resolve your issues if they were included and considered separately from the rest.
Keep plugging away. It could be technical. Or maybe it is real and SARS-CoV-2 doesn't care if its ends are "frayed".
You may actually be on the track of something extremely important.
Individual viral particles with "frayed ends" may be "duds". If you look at Covid19 tracking data, it seems that most people that catch Covid19 fail to transmit to somebody else (it fizzles out for these) while a few people infect lots of others. It could be that "failure to infect others" involves the accumulation of bad ends.
Those among the "there is no virus crowd", cite studies where transmission failed. (These were in the 1970s, before ethics rules probably forbid them now.) Perhaps this is a matter in timing, where bad ends accumulate towards the end of an infection cycle.
ends 6/ Twitter, starting today, no longer allows guest web browsing. So I can't follow your debate with Kevin unless I sign up. Please ask him what he thinks about the possibility that some of your end concern is actually real, not merely technical, and may relate to "fizzle out". JJ Couey (Gigaohm) is somebody else that is also interested in another hypothesis for "fizzle out".
edit: ends 4/ "...just within the polyA tract..." should read "...just left of the polyA tract....". "...just within the 5' cap..." should read "...just right of the 5' cap..."
Without the ends, one cannot establish validity of the entire genome.
ends 1/ For the human genome project, Pres Clinton in his last year had a press conference with the two teams (Private Ventner vs Public NIH) present announcing its "completion". (Or maybe Bush in his first year, I don't remember for sure.) In any case, all the genome scientists knew that it wasn't really "complete", just the first phase, the easier stuff. Large chunks of the sequencing could be aligned onto the (classical) genetic map, but they could not rule out unknown gaps between the known sequenced chunks. That came later, perhaps, but I'm not really sure if there are still some gaps remaining even >20yrs later. I haven't followed it that closely.
ends 2/ The technical issue with the resistant portion involves "repetitive" DNA. The concept overlaps with what is sometimes (falsely?) referred to as "junk" DNA.
Assembly programs like Megahit would have a problem with sequential repeats if the k-mers are too small. Even large k-mers (maybe 81nt), could not deal with a tract of hundreds of small repeats.
Assembly programs could even have a problem with well separated repeats. Well separated repeats within the SARS-CoV-2 genome could present problems for Megahit. I mentioned something about "subgenomic RNA junctions" in part "6/". These "junctions" are generated by the repeats, which are subject to "cut and paste" operations (actually, more like, "jump from one repeat to the next"). For the human genome, "cut and paste" operations result in birth defects (eg Down's syndrome) and cancers.
ends 3/ The problem with failure to "complete" (in the absolute sense) the human genome probably could not be solved before very long read technology such as Nanopore and Pacific Biosystems came about.
None of this directly addresses Covid19 ends, except as context. First lesson from the human genome project: "Take your victory where you can" (99% glass full), and "keep plugging away at the rest" (1% glass empty).
Second lesson from the HGP: "Failure to resolve gaps do not invalidate the concept of the human genome", nor does it mean that humans don't exist.
ends 4/ Apart from the variable length of the 3' PolyA tract, which is real and may have some biological meaning, you are complaining about high sequence variation just within the polyA tract, and just within the 5' cap. I don't know if this variation is real and has biological meaning for individuals within a "swarm", or if it is a technical issue (sequencing errors, not real variation), or a combination of both.
Recall that the Wuhan sequencing project had 3 phases, the last being a very special technique for the ends. I have not yet read about this technique. I don't know if these special end reads are included in your dataset, nor do I know if they would resolve your issues if they were included and considered separately from the rest.
Keep plugging away. It could be technical. Or maybe it is real and SARS-CoV-2 doesn't care if its ends are "frayed".
ends 5/ "Just one more thing" - Columbo
You may actually be on the track of something extremely important.
Individual viral particles with "frayed ends" may be "duds". If you look at Covid19 tracking data, it seems that most people that catch Covid19 fail to transmit to somebody else (it fizzles out for these) while a few people infect lots of others. It could be that "failure to infect others" involves the accumulation of bad ends.
Those among the "there is no virus crowd", cite studies where transmission failed. (These were in the 1970s, before ethics rules probably forbid them now.) Perhaps this is a matter in timing, where bad ends accumulate towards the end of an infection cycle.
You may be the key that reconciles the two camps.
ends 6/ Twitter, starting today, no longer allows guest web browsing. So I can't follow your debate with Kevin unless I sign up. Please ask him what he thinks about the possibility that some of your end concern is actually real, not merely technical, and may relate to "fizzle out". JJ Couey (Gigaohm) is somebody else that is also interested in another hypothesis for "fizzle out".
edit: ends 4/ "...just within the polyA tract..." should read "...just left of the polyA tract....". "...just within the 5' cap..." should read "...just right of the 5' cap..."