owlmonkey

One study says ~38 individual base mutations per generation, but that increases by about 2 bases per year of the father's age, which is still not much given 6 billion base pairs in humans. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548427/) These studies, however, are missing rearrangements and other spontaneous structural changes which might not modify the genes at all but might change their expression or dosage. We don't have enough data yet about structural mutation rates, the technology to assess that at scale and low cost is only coming online now. Not sure about the incident rate, but since the guidelines for reporting have widened so much in the last decade that might mask any ability to really know.

If one of these jackknifes enroute is that called a 'snowcrash'?

It's politics. You can't survive here politically proposing as-of-right building permits and across the board upzoning. But you can move the needle in the right direction.

Building is the one variable of the three he cites that is reasonable to encourage IMO. But the pre-existing population here has demonstrated a clear disdain for building. So who is really to blame then for the inflation and displacement and thereby the gentrification?

TILT sounds like an interesting idea. In San Francisco I suspect our best bet is through California State laws offering density bonuses or provide as-of-right building in some form, that overrides local planning constraints. For example, AB 2501 is currently in the local government committee but is being voted on this Wednesday: http://leginfo.legislature.ca.gov/faces/billNavClient.xhtml?...

If you feel compelled like me to support more housing in the bay area, please write or call these Assemblymembers in the local government committee and ask them to support it before Wednesday at 1:30 pm Pacific, even if you're not in their district:

Susan Talamantes Eggman (Chair) - http://asmdc.org/members/a13 Marie Waldron (Vice-Chair) - https://ad75.asmrc.org/ Luis A. Alejo - http://asmdc.org/members/a30/ Susan A. Bonilla - http://asmdc.org/members/a14/ David Chiu - http://asmdc.org/members/a17/ Ken Cooley - http://asmdc.org/members/a08/ Beth Gaines - https://ad06.asmrc.org/ Richard S. Gordon - http://asmdc.org/members/a24/ Eric Linder - https://ad60.asmrc.org/

The implication is that people are illegally listing multiple properties that they own or rent, but this analysis doesn't rule out the cases where someone hires a professional property manager to list their place on AirBnB while they're on vacation or away. That property manager will have multiple "whole home" listings but there's nothing illegal about it.

But we shouldn't expect an unbiased analysis from a site like insideairbnb.com, which is a partisan anti-airbnb advocacy project.

I don't follow your train of thought on in-laws. Because they're small, they're unlikely to serve for 'hosted' rentals and more likely to be only short term rentable up to 90 days. e.g. when the existing renter in the in-law goes on vacation. So why does this proposition want to ban that use case entirely instead of just restrict it to 75 days?

Not any more, and especially not compared to the HiSeq 2000 used for that paper. PacBio's raw sequencing cost is now about on par with where the HiSeq was when it first launched. And because of the error profile you don't need as much coverage and it's a lot less effort to assemble. So the total project cost now is comparable, even if the raw sequencing cost is higher still.

If they were really interested in discovering unknown genes, they should have used PacBio to sequence the whole genome instead of just 83% of it via Illumina. That assembly quality ("a contig N50-length of 5.4 kb and a scaffold N50-length of 470 kb") is truly awful compared to a PacBio assembly.

Better to have people looking in the wrong place, in a way that they will look indefinitely

Totally agree with you on the computation costs.

In some slides in February ONT hinted at why they had to go to a full wet sample prep and it related to input DNA amounts I believe. Their new sample prep they said allowed them to reduce their input DNA amounts to similar amounts as competitor sequencers, but without that new prep it took 10,000x more DNA to load. I guess raw DNA just doesn't load into the nanopores very easily, so it took that much higher concentration. Two years ago they claimed you could load raw blood into a chip after a 5 minute prep, but I'm guessing they will back away from that claim now since this wet chemistry is needed to get reasonable loading.

This to me implies that all nanopore technology under development will encounter similar problems. They really need biological or magnetic bead processes to "load" DNA through the pores in one form or another - or else need prohibitively high DNA concentrations and amounts - so that will mean wet chemistry.

Ya the MinIon is more of a DNA sensor than a sequencer in its current incarnation, but awesome for portability. Super expensive per base though. If they can't improve the cost significantly along with the accuracy it will never be a competitive sequencer.

You're wrong about the PacBio though, the raw reads are random and cancel out easily with consensus. PacBio is the least biased and therefore the most consensus accurate next-gen sequencer available. See my other comments for some citations.

Totally agree. It is at best a semi-portable sensor (with wet prep) not a sequencer. Cost would be another big obstacle for using MinIon on human data. At about 100 megabases and $1000 per cell that's three orders of magnitude more expensive per base than a HiSeq X. (edit: spelling)

One doesn't need CCS anymore, though it is still an option for shorter insert lengths. The errors are more random than other platforms, so they resolve easily with consensus. You just need 20x coverage or more, depending upon the application. With enough coverage you generally get better accuracy than any other platform because it's the least biased technology.

CCS still works really well if you want incredibly high accuracy. See this paper and figure 3 for Q90 quality reads: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3811116/

But most people don't need that for their applications. So just regular consensus using PacBio data alone is sufficient for excellent (Q60 or better) consensus accuracy: https://github.com/PacificBiosciences/GenomicConsensus/blob/...

PacBio is ultimately more accurate than Illumina given consensus. Illumina has some systemic bias so the ultimate accuracy tops out around Q40-Q50 (same errors just repeat themselves) and PacBio will get you closer to Q60-Q70 because the random errors resolve out. So it's the most accurate platform actually. This singuler MinIon read however was barely mappable to the reference, so it looks pretty poor quality. But without more reads we don't quite yet know what the systemic error profile will be though for it. That's why they're adding more pore types, they say, to get multiple systemic error profiles to try to cancel some out.

Another researcher was sequencing Brook before she died, and I believe using the PacBio sequencer to get the full sequence (instead of an incomplete "whole" sequence using Illumina sequencers.) Hopefully something useful will emerge. Here is a link to a video of Brook on Katie Couric's show: http://katiecouric.com/features/is-there-a-way-to-slow-your-...

Haven't tested on 3.2.x yet but the GC was never the issue for our stress tests. Bugs in the socket layers were killing us. Better under 2.10.9 but still not completely resolved.

We have a product that has a C# web app deployed via mono on a linux box commercially shipping for four years. What I found was that with mono 2.10.6 it was fine as long as it was not loaded heavily, but under stress it would have stability issues. The socket layer was rewritten since then however and I've had less issues with 2.10.8/9 but still fails under heavy load. More fixes have gone into mono 3. My sense is that it's getting better but not nearly as battle tested compared to JVM-based network stacks. So if I was coding a large scale web service I'd consider Scala first.

Some interesting structural differences are not captured by 23andMe nor even with technology like Ion Torrent, for example repeat sequences related to ALS, Huntington's, etc. To get the full picture ultimately you'll need a full sequence with longer read lengths to span the structural variants, and you'll also want the methylation/epigenetic markers which convey which genes are turned on or turned off. Just knowing you have the gene doesn't mean nearly as much without knowing if it is turned on!

I agree PacBio doesn't have the high-throughput of Illumina or similar amplification approaches yet, but from last month's AGBT conference papers it's clear that it's now more accurate than other systems with typical coverage (no bias, covers repeats, Q50-60, etc.)

PacBio has average read length now of about 5000 bp whereas 454 is still only about 1000 bp.