I use Sipgate as my voicemail on Android - the free local 'landline' number certainly beats a SkypeIn rental, is cheap (free on many tariffs) for the caller, and emails the audio file to my gmail account so I can pick it up anywhere in the world I have wifi or 3G (it plays nicely from the gmail client's audio preview). It's also easy to set up Sipgate with Sipdroid without needing to uses PBXes:
Not for annotation, but for the initial alignment of NGS reads to the reference genome. BWA, Bowtie, and SOAP2 all use the Burrows-Wheeler transform, and are in common use. For variant calling and functional annotation we'd use other tools, e.g.:
'What I'd like to be able to do is have the data, and be able to look up how any discoveries later on map to what I've got. Is that possible?'
You can't do genome sequencing, or even SNP chip genotyping, in a DIY lab, so you'll have to involve a large company or research centre at some point. But you can do this anonymously (e.g. through a physician) and get hold of the raw data afterwards to analyse as you please, assuming you have the technical knowledge to make sense of it. Illumina is one company that provides this sort of service for whole genomes via physicians at a cost of $10,000-20,000 USD:
'If you need the raw data again, you can just resequence the sample.'
See my reply above to another post - this is exactly the approach that some centres are taking. But as you say, some samples can't be regarded as a consumable resource (e.g. archival clinical material is often only available in limiting quantities).
'It's been a couple of years since we saved the primary [raw image] data. It is cheaper to redo the sequence and pull it out of the freezer. There are 5,000 tubes in a freezer. Storing a tube isn't very expensive. Storing 1 Terabyte of data that comes out of that tube costs half as much as the freezer! People [like Ewan Birney at EBI] are working on very elaborate algorithms for storing data, because you can't compress bases any more than nature already has. The new paradigm is, the bases are here, only indicate the places where the bases are different . . . In 2-3 years, you'll wonder about even storing the bases. And forget about quality scores.'
'Also, my understanding is that most uses don't require sequencing the entire genome, but rather just a small subset of it.'
Very small subsets (e.g. individual genes) are still done the 'traditional' way (1990s technology!). Intermediate subsets (like the 'exome') are now done using a pre-selection 'capture' process ('target enrichment') followed by analysis on the same 'next generation' instruments that are used for whole genomes. Right now, this makes sense economically, since it requires less capacity (fewer consumables and less run time) on the expensive sequencers. But as sequencing prices continue to drop, we'll probably reach a point where it's cheaper to do the whole genome than any significant subset (since the 'capture' process is also fairly expensive). Cheaper to do the wet lab stuff, anyway - whole genomes also require much more processing power than useful subsets like exomes.
Yes, the incoming (and intermediate) data sets are huge. You don't just sequence each base once, but 30-50 times over on average (required to call variants accurately). And you don't want to throw this data away, since analysis algorithms are improving all the time. But it's true that the final 'diff' to the reference sequence is very small, and has been compressed to as little as 4Mb in one publication:
Progress in SNP chips, though they were a big breakthrough when introduced and remain very important in research, has been pretty static compared to the dramatic speed with which 'next generation' sequencing technologies have brought down the cost and increased the amount of data we have to cope with. Whole genome sequencing is on an entirely different scale - 3 billion bases rather than a million. Even an 'exome' (the sequence of all the actual genes in your genome) runs to about 40 million bases.
It's computationally expensive and pretty much subject to Moore's Law (though improved algorithms like Burrows-Wheeler alignment have helped to speed things up in the last couple of years). So it's getting cheaper, but not fast enough to keep up with the expected deluge of data. If you're just interested in sequencing a fixed number of genomes you benefit from both cheaper/faster sequencing and cheaper/faster processing power. But if you're a major genome centre, be prepared for some serious IT investment, or the bottleneck will increasingly be the speed with which you can crunch the data.
"What you have to understand is the extreme speed with which the technology blossomed," Bors said. "When Earth first became conscious, it used all its resources to spread the technology as efficiently as possible. The first transceiver was implanted in March, let's say, and all Earth was integrated by Christmas. The first clear notion anybody off-planet had of what had actually happened was when the warcraft were launched."
This was written in 1987, 6 years before Vinge's essay on the Singularity, which references it. And here, before anyone had heard of the Cylon Hybrids or even the Borg, is Swanwick's sample of a 'Comprise' brain at work:
"Rotate grating six raise two and rotate again reroute quote the Comprise agree in principle but with reservations unquote raise the vial of eagle's blood reroute using Allen wrench adjust the potentiometer to the red mark reroute ship to Sanfrisco marked green code green reroute injecting kerosene between vascular stations seventeen and twelve reroute bedding excavation-"
'This is very important, Mr. Gant, you must think in German. You can't think in English and transpose it. You must think in German. Do you think you can do that, Mr. Gant?'
It's not just GPL3, though MS uses GPL3 as an example:
'"Excluded License" means any license requiring, as a condition of use, modification and/or distribution of the software subject to the license, that the software or other software combined and/or distributed with it be (i) disclosed or distributed in source code form; (ii) licensed for the purpose of making derivative works; or (iii) redistributable at no charge. Excluded Licenses include, but are not limited to the GPLv3 Licenses. For the purpose of this definition, "GPLv3 Licenses" means the GNU General Public License version 3, the GNU Affero General Public License version 3, the GNU Lesser General Public License version 3, and any equivalents to the foregoing.'
(i) & (ii) would apply equally to (e.g.) GPL2, which lacks the 'Tivo' clause. Of course you could argue that use in a 'Tivoized' environment is against the spirit of GPL2, if not its letter.
'Radium - Life-Giving Element...deals DEATH in Hands of Quacks'
The whole magazine is worth a look, incidentally. The next item ('Flying Tanks - War's Deadliest Weapon'), nicely illustrated by a formation of biplane-tanks flying into battle, might qualify as 'dead' technology, but Wikipedia suggests there were subsequent experiments:
'As I continue to write Volumes 4 and 5, I'll need to refer to topics that belong logically in Volumes 1--3 but weren't invented yet when I wrote those books. Instead of putting such material artificially into Volumes 4 or 5, I'll put it into fascicle form. The first such fascicle is in fact ready now (see above): It describes MMIX, a RISC machine that is used in Volume 4A; MMIX will also take the place of MIX in all subsequent editions of Volumes 1, 2, and 3.
Download the 16 Feb 2004 version of Volume 1 Fascicle 1 (583KB of compressed PostScript) (this old version is however no longer being maintained)':
The BBC is reporting Apple shares in Frankfurt are down 7% already, and CNN notes that Apple is due to release an earnings report tomorrow. So I guess the announcement was particularly carefully timed, not only falling on a US public holiday, but coming just before an earnings report that will presumably be positive and help to mitigate the damage when the US market re-opens. But that's just good business, of course. Best wishes to Steve!
'That's a google search for who discovered DNA...If crick is listed at all, he is listed second in every case on the first page of results.'
- DNA was discovered by Frederick Miescher in the 19th century.
- The original DNA _structure_ paper listed Watson and Crick as authors in that order: http://www.nature.com/nature/dna50/archive.html This is presumably why they've been listed this way ever since.
- If either is mentioned in the default 2-line results excerpt when I run your Google search, both are (with one exception).
- The first hit mentions only Watson in this excerpt, but in the specific context of discovering the correct base pairing, which was indeed his individual insight, as he explains here:
'I also am curious how much it costs there, any single Android phone in any carrier here wants 200 out of my pocket and a 2 year contract, the same ATT wants for the iPhone.'
It's probably easiest to compare the non-contract prices. An 8Gb 3GS is £428, a 16Gb 4 is £510, and a 32Gb 4 is £612. Android phones start at £60 for the most basic models (resistive screen, Android 2.1, PAYG, no contract). There are plenty of more capable models with capacitive screens in the £100-200 price range. Any of these can be used with very reasonable PAYG data tariffs (a single payment of £20 will buy you 6 months worth of net access on T-Mobile). Voice calls are on top of that, so a contract may be worthwhile if you're a heavy user.
With these sorts of prices, Apple is obviously only competing over here at the (lucrative!) high end of the market (though I'm sure if they chose they could introduce a budget model costing not much more than the £193 8Gb Touch - presumably this would cannibalise too many sales from the expensive phones).
'Android and Itouch? they'll never figure it out.'
I'm not sure I can figure it out. There's a good reason why the iTouch has gone 'virtually unchallenged'. In most of the world, competing smartphones can be bought very cheaply without a contract. I can get a basic PAYG/unlockable Android 2.2 phone locally for the equivalent of $80 USD. So there's little market for a PMP/WiFi-only device (why carry two gadgets rather than one?). But perhaps such a device will do better in the US, where the networks distort the market and cheap Android phones seem to be less readily available.
Apple, however, is in a unique position worldwide. They know they can sell iPhones at a high margin and often have lucrative deals with the networks to take an additional cut from contracts. Selling a cheaper iPhone model would endanger this, so they've chosen instead to make a deliberately limited device that still incoporates most of the iPhone technology, an 'iPhone without a phone' astutely branded as an 'iPod'. They can get away with this because of their high profile brand and genuinely attractive technology, the iTunes and app store 'ecosystems', and the large existing iPod user base looking to upgrade. The iTouch presumably has a much lower margin; it can't be much cheaper to produce than the iPhone given the component costs, but is sold for substantially less (£249 vs £599 for the 32Gb models in the UK). But a profit is still a profit, and iTouch customers may well be future (and more lucrative) iPhone customers.
Slashdot Mirror
I use Sipgate as my voicemail on Android - the free local 'landline' number certainly beats a SkypeIn rental, is cheap (free on many tariffs) for the caller, and emails the audio file to my gmail account so I can pick it up anywhere in the world I have wifi or 3G (it plays nicely from the gmail client's audio preview). It's also easy to set up Sipgate with Sipdroid without needing to uses PBXes:
http://www.hutsby.net/2010/03/how-to-sipgate-and-sipdroid.html
'Of course, that may just be the plateau before it falls off the next cliff.'
The next cliff is already emerging through the mist, e.g.:
http://www.genomeweb.com/sequencing/life-tech-outlines-single-molecule-sequencing-long-pieces-dna
http://www.wired.com/wiredscience/2011/01/guest-post-introduction-to-nanopore-sequencing/
It's not clear which 'single-molecule' technology will eventually win out, but it will almost certainly have the word 'nano' in it somewhere.
Not for annotation, but for the initial alignment of NGS reads to the reference genome. BWA, Bowtie, and SOAP2 all use the Burrows-Wheeler transform, and are in common use. For variant calling and functional annotation we'd use other tools, e.g.:
http://www.broadinstitute.org/gsa/wiki/index.php/Best_Practice_Variant_Detection_with_the_GATK_v2
http://www.openbioinformatics.org/annovar/
'What I'd like to be able to do is have the data, and be able to look up how any discoveries later on map to what I've got. Is that possible?'
You can't do genome sequencing, or even SNP chip genotyping, in a DIY lab, so you'll have to involve a large company or research centre at some point. But you can do this anonymously (e.g. through a physician) and get hold of the raw data afterwards to analyse as you please, assuming you have the technical knowledge to make sense of it. Illumina is one company that provides this sort of service for whole genomes via physicians at a cost of $10,000-20,000 USD:
http://www.everygenome.com/
For much less money (say $200), you can have genotying done and download the SNP calls for future analysis, e.g.:
http://www.snpedia.com/index.php/23andMe
'If you need the raw data again, you can just resequence the sample.'
See my reply above to another post - this is exactly the approach that some centres are taking. But as you say, some samples can't be regarded as a consumable resource (e.g. archival clinical material is often only available in limiting quantities).
'The incoming data is image-based, so yes, it will be huge.'
The image data is routinely discarded by at least some major centres; the raw sequence and quality data alone is huge enough to be a major issue! See:
http://www.bio-itworld.com/news/09/16/10/Broad-approach-genome-sequencing-partI.html
'It's been a couple of years since we saved the primary [raw image] data. It is cheaper to redo the sequence and pull it out of the freezer. There are 5,000 tubes in a freezer. Storing a tube isn't very expensive. Storing 1 Terabyte of data that comes out of that tube costs half as much as the freezer! People [like Ewan Birney at EBI] are working on very elaborate algorithms for storing data, because you can't compress bases any more than nature already has. The new paradigm is, the bases are here, only indicate the places where the bases are different . . . In 2-3 years, you'll wonder about even storing the bases. And forget about quality scores.'
'Also, my understanding is that most uses don't require sequencing the entire genome, but rather just a small subset of it.'
Very small subsets (e.g. individual genes) are still done the 'traditional' way (1990s technology!). Intermediate subsets (like the 'exome') are now done using a pre-selection 'capture' process ('target enrichment') followed by analysis on the same 'next generation' instruments that are used for whole genomes. Right now, this makes sense economically, since it requires less capacity (fewer consumables and less run time) on the expensive sequencers. But as sequencing prices continue to drop, we'll probably reach a point where it's cheaper to do the whole genome than any significant subset (since the 'capture' process is also fairly expensive). Cheaper to do the wet lab stuff, anyway - whole genomes also require much more processing power than useful subsets like exomes.
Yes, the incoming (and intermediate) data sets are huge. You don't just sequence each base once, but 30-50 times over on average (required to call variants accurately). And you don't want to throw this data away, since analysis algorithms are improving all the time. But it's true that the final 'diff' to the reference sequence is very small, and has been compressed to as little as 4Mb in one publication:
http://www.ncbi.nlm.nih.gov/pubmed/18996942
Progress in SNP chips, though they were a big breakthrough when introduced and remain very important in research, has been pretty static compared to the dramatic speed with which 'next generation' sequencing technologies have brought down the cost and increased the amount of data we have to cope with. Whole genome sequencing is on an entirely different scale - 3 billion bases rather than a million. Even an 'exome' (the sequence of all the actual genes in your genome) runs to about 40 million bases.
"How about the cost of analysis of said genomes?"
It's computationally expensive and pretty much subject to Moore's Law (though improved algorithms like Burrows-Wheeler alignment have helped to speed things up in the last couple of years). So it's getting cheaper, but not fast enough to keep up with the expected deluge of data. If you're just interested in sequencing a fixed number of genomes you benefit from both cheaper/faster sequencing and cheaper/faster processing power. But if you're a major genome centre, be prepared for some serious IT investment, or the bottleneck will increasingly be the speed with which you can crunch the data.
When I read it, the book was Michael Swanwick's excellent 'Vacuum Flowers':
http://tenser.typepad.com/tenser_said_the_tensor/2005/02/earthless.html
http://www.infinityplus.co.uk/nonfiction/vacuum.htm
"What you have to understand is the extreme speed with which the technology blossomed," Bors said. "When Earth first became conscious, it used all its resources to spread the technology as efficiently as possible. The first transceiver was implanted in March, let's say, and all Earth was integrated by Christmas. The first clear notion anybody off-planet had of what had actually happened was when the warcraft were launched."
This was written in 1987, 6 years before Vinge's essay on the Singularity, which references it. And here, before anyone had heard of the Cylon Hybrids or even the Borg, is Swanwick's sample of a 'Comprise' brain at work:
"Rotate grating six raise two and rotate again reroute quote the Comprise agree in principle but with reservations unquote raise the vial of eagle's blood reroute using Allen wrench adjust the potentiometer to the red mark reroute ship to Sanfrisco marked green code green reroute injecting kerosene between vascular stations seventeen and twelve reroute bedding excavation-"
'Tolkien Tolkien Tolkien Tolkien Tolkien Tolkien Tolkien Tolkien Tolkien Mushroom! Mushroom! Tolkien Tolkien Tolkien Tolkien A SNAKE! A SNAKE! Oh it's a snake!'
Careful, they're already suing over this:
http://www.weebls-stuff.com/toons/special+edition/
'I still get surprised everytime I see someone on Slashdot buying disks.'
Sometimes you just want to watch a movie, and: http://xkcd.com/14/
'This is very important, Mr. Gant, you must think in German. You can't think in English and transpose it. You must think in German. Do you think you can do that, Mr. Gant?'
It's not just GPL3, though MS uses GPL3 as an example:
'"Excluded License" means any license requiring, as a condition of use, modification and/or
distribution of the software subject to the license, that the software or other software combined
and/or distributed with it be (i) disclosed or distributed in source code form; (ii) licensed for the
purpose of making derivative works; or (iii) redistributable at no charge. Excluded Licenses include,
but are not limited to the GPLv3 Licenses. For the purpose of this definition, "GPLv3 Licenses" means
the GNU General Public License version 3, the GNU Affero General Public License version 3, the GNU
Lesser General Public License version 3, and any equivalents to the foregoing.'
(i) & (ii) would apply equally to (e.g.) GPL2, which lacks the 'Tivo' clause. Of course you could argue that use in a 'Tivoized' environment is against the spirit of GPL2, if not its letter.
'Wouldn't we class these "tools" as "snake-oil" or psuedo-science by today's standards?'
They were snake oil even by the standards of the time. From 'Popular Science' magazine in 1932:
http://books.google.co.uk/books?id=SSgDAAAAMBAJ&pg=PA9
'Radium - Life-Giving Element...deals DEATH in Hands of Quacks'
The whole magazine is worth a look, incidentally. The next item ('Flying Tanks - War's Deadliest Weapon'), nicely illustrated by a formation of biplane-tanks flying into battle, might qualify as 'dead' technology, but Wikipedia suggests there were subsequent experiments:
http://en.wikipedia.org/wiki/Winged_tank
...and until Vol.1 is updated:
http://www-cs-faculty.stanford.edu/~uno/taocp.html
'As I continue to write Volumes 4 and 5, I'll need to refer to topics that belong logically in Volumes 1--3 but weren't invented yet when I wrote those books. Instead of putting such material artificially into Volumes 4 or 5, I'll put it into fascicle form. The first such fascicle is in fact ready now (see above): It describes MMIX, a RISC machine that is used in Volume 4A; MMIX will also take the place of MIX in all subsequent editions of Volumes 1, 2, and 3.
Download the 16 Feb 2004 version of Volume 1 Fascicle 1 (583KB of compressed PostScript) (this old version is however no longer being maintained)':
http://www-cs-faculty.stanford.edu/~uno/fasc1.ps.gz
It's only Volume 4A. Algorithms to generate Dho-Nha geometry curves in polynomial time aren't covered until Volume 4C, so he's safe for the moment.
Presumably it's a 're-imagining' of this:
http://www.astrodispatch.com/wp-content/uploads/2010/12/10/9725f_warlock-the-armageddon-205x300.jpg
Yes, what on Middle Earth were they thinking? It should, of course, be 'dwarrowed'.
'now if this was a stock market news site...'
The BBC is reporting Apple shares in Frankfurt are down 7% already, and CNN notes that Apple is due to release an earnings report tomorrow. So I guess the announcement was particularly carefully timed, not only falling on a US public holiday, but coming just before an earnings report that will presumably be positive and help to mitigate the damage when the US market re-opens. But that's just good business, of course. Best wishes to Steve!
'That's a google search for who discovered DNA...If crick is listed at all, he is listed second in every case on the first page of results.'
- DNA was discovered by Frederick Miescher in the 19th century.
- The original DNA _structure_ paper listed Watson and Crick as authors in that order:
http://www.nature.com/nature/dna50/archive.html
This is presumably why they've been listed this way ever since.
- If either is mentioned in the default 2-line results excerpt when I run your Google search, both are (with one exception).
- The first hit mentions only Watson in this excerpt, but in the specific context of discovering the correct base pairing, which was indeed his individual insight, as he explains here:
http://www.youtube.com/watch?v=Ecyvr8a-0D0
Nobody is going to forget Crick, unless of course the Palin-Voldemort campaign is successful in 2012 and all books are burnt.
At least one other study, conducted on a Mr JT Kirk of Iowa, has reported results consistent with your experience:
http://en.wikipedia.org/wiki/Elaan_of_Troyius
'I also am curious how much it costs there, any single Android phone in any carrier here wants 200 out of my pocket and a 2 year contract, the same ATT wants for the iPhone.'
It's probably easiest to compare the non-contract prices. An 8Gb 3GS is £428, a 16Gb 4 is £510, and a 32Gb 4 is £612. Android phones start at £60 for the most basic models (resistive screen, Android 2.1, PAYG, no contract). There are plenty of more capable models with capacitive screens in the £100-200 price range. Any of these can be used with very reasonable PAYG data tariffs (a single payment of £20 will buy you 6 months worth of net access on T-Mobile). Voice calls are on top of that, so a contract may be worthwhile if you're a heavy user.
With these sorts of prices, Apple is obviously only competing over here at the (lucrative!) high end of the market (though I'm sure if they chose they could introduce a budget model costing not much more than the £193 8Gb Touch - presumably this would cannibalise too many sales from the expensive phones).
'Android and Itouch? they'll never figure it out.'
I'm not sure I can figure it out. There's a good reason why the iTouch has gone 'virtually unchallenged'. In most of the world, competing smartphones can be bought very cheaply without a contract. I can get a basic PAYG/unlockable Android 2.2 phone locally for the equivalent of $80 USD. So there's little market for a PMP/WiFi-only device (why carry two gadgets rather than one?). But perhaps such a device will do better in the US, where the networks distort the market and cheap Android phones seem to be less readily available.
Apple, however, is in a unique position worldwide. They know they can sell iPhones at a high margin and often have lucrative deals with the networks to take an additional cut from contracts. Selling a cheaper iPhone model would endanger this, so they've chosen instead to make a deliberately limited device that still incoporates most of the iPhone technology, an 'iPhone without a phone' astutely branded as an 'iPod'. They can get away with this because of their high profile brand and genuinely attractive technology, the iTunes and app store 'ecosystems', and the large existing iPod user base looking to upgrade. The iTouch presumably has a much lower margin; it can't be much cheaper to produce than the iPhone given the component costs, but is sold for substantially less (£249 vs £599 for the 32Gb models in the UK). But a profit is still a profit, and iTouch customers may well be future (and more lucrative) iPhone customers.