Essay! GAH!
Ok so I have this essay. I don't want to do the essay. BUT I HAVE TO.
So here I am warming up my writing neurons.
So For the Essay I gots to write about three classics in my field. Classic Papers that is. Let me tell you the ones I chose:
1. Watson and Crick's Structure of DNA. 1953.
2. Altschul et al. Basic Local Alignment Search Tool. 1990.
3. Venter. Whole Genome Random Sequencing and Assembly of Haemophilus influenxae Rd. 1995.
Now let me tell you What They're About:
1. These dudes, Watson and Crick, they're in Oxford. Watson's a seriously precocious young PhD and Crick's gettin on the old side of young with no doctorate. Watson realizes Linus-motherfucking-Pauling has it wrong with the phosphate groups hydrogen bonding amoung themselves, because obviously in an aqueous system that shit'd be ionized (silly physicist), plus Wilkins showed him some of Rosalind's work, and damn if that xray diffraction didn't make it look solvable. So he and Watson played with tinker toys till they figured it out. It got them a Nobel, but poor Dr. Franklin had died (damn X-rays) at a young age from ovarian cancer, so they gave the award to her boss, Wilkins.
I know the story and more probably because of Watson's memoir of the discovery: "The Double Helix" which pissed off just about everybody. In fact the university publisher dropped the book, which was then picked up by a commercial publisher. The book is said to have changed the way the public viewed scientists and the way they work.
Watson is known for being an asshole. His wikipedia article has a nice summary of offensive things he's said. If they don’t make you cringe, you’ve prolly got what he has. Watson's famous quoted suppositions on race and intelligence earned him a suspension as the director of Cold Spring Harbor in 2007 and probably had something to do with his retirement shortly thereafter. My mentor who'd worked at Cold Spring Harbor, well I won't quote her, but her comments support the Asshole theory of Watson.
Still he is Watson of the Watson strand of DNA (the other is named for Crick). And He, like Venter are rock star scientists. I’d totally take my picture with them making faux gansta signs and post them to facebook if they universe is ever kind enough to give me that opportunity. I’ll tell you more about Venter in a second. Incidentally, Watson hates Venter and called him “Hitler”.
2. Altschul et al’s Basic Local Alignment Search Tool (BLAST) was the most cited paper in the 90’s. Everyone in bioinformatics recognizes the name of accidental first author Stephen Altshul, who got his position by virtue of alphabetical precedence. BLAST was the brainchild of last author David Lipman, the Director of the National Center for Biotechnology Information (NCBI) since 1989. Lipman is a trained physician with absolutely no drama in his wikipedia entry and obviously leads a distinguished career.
So what is this BLAST? Well, like “google”, “BLAST” is a verb with ubiquitous usage. I got taught how to BLAST as an undergrad and I bet children in high school and perhaps grade school are now BLASTing their names for fun.1 To BLAST is to identify variants of your nucleotide (or protein) sequence across all (sequenced) domains of life. (Damn that sampling bias.) Since we DNA-based life are remarkably similar metabolically, it’s possible to make a strong guess on the function of genes based on knowledge of another version of that gene in another organism. Not everything transfers over, but it’s somewhere to start.
Lipman and his team crafted the algorithm so that it could run efficiently. Progressive alignment, BLAST’s precurser, was too inefficient for the wealth of sequence data available at the time. Unlike earlier alignment programs, BLAST’s approach doesn’t perform exhaustive calculations to determine the absolute best answer to any sequence alignment problem it’s given. Instead it finds you solutions that are not significantly different from perfect. Which is all you needed anyway. Almost twenty years later, BLAST remains a cornerstone tool of bioinformaticians.
3. In the early 90’s, we’d begun sequencing whole genomes of viruses. Since sequencing reactions may only capture fragments of the genome, assembly of fragments becomes nontrivial. At first, the genome sequencing progressed by the primer-walking method where the genome is sequenced systematically from end to end. Primers for the next bit of sequence are chosen from the ends of the last sequence. Then came the shotgun method. Nice name eh? It’s a characterization of the approach. Forget primer walking. Let’s just sequence a bunch of this stuff randomly and then have a computer knit it all together. It sure worked for viruses. Bacteria however, have much larger genomes. The assembly problem gets orders of magnitude worse.
Venter’s paper “Whole Genome Random Sequencing and Assembly of Haemophilus influenxae Rd” is a classic, not simply because it describes the first complete genome of a free living organism, but it describes their solution to the assembly problem of shotgun sequencing.
Whew…. I think that’s a good first draft to build on. Pardon me as I read a bit more and edit. Draft 2 will be coming up in a few hours.
1. -Well, a few anyway. Go here, enter your name in the big box to find your totem. (I’m Candidatus Methanoregula boonei 6A8, an Archea. Archea are the ultimate outgroup. Interesting… ) .
So here I am warming up my writing neurons.
So For the Essay I gots to write about three classics in my field. Classic Papers that is. Let me tell you the ones I chose:
1. Watson and Crick's Structure of DNA. 1953.
2. Altschul et al. Basic Local Alignment Search Tool. 1990.
3. Venter. Whole Genome Random Sequencing and Assembly of Haemophilus influenxae Rd. 1995.
Now let me tell you What They're About:
1. These dudes, Watson and Crick, they're in Oxford. Watson's a seriously precocious young PhD and Crick's gettin on the old side of young with no doctorate. Watson realizes Linus-motherfucking-Pauling has it wrong with the phosphate groups hydrogen bonding amoung themselves, because obviously in an aqueous system that shit'd be ionized (silly physicist), plus Wilkins showed him some of Rosalind's work, and damn if that xray diffraction didn't make it look solvable. So he and Watson played with tinker toys till they figured it out. It got them a Nobel, but poor Dr. Franklin had died (damn X-rays) at a young age from ovarian cancer, so they gave the award to her boss, Wilkins.
I know the story and more probably because of Watson's memoir of the discovery: "The Double Helix" which pissed off just about everybody. In fact the university publisher dropped the book, which was then picked up by a commercial publisher. The book is said to have changed the way the public viewed scientists and the way they work.
Watson is known for being an asshole. His wikipedia article has a nice summary of offensive things he's said. If they don’t make you cringe, you’ve prolly got what he has. Watson's famous quoted suppositions on race and intelligence earned him a suspension as the director of Cold Spring Harbor in 2007 and probably had something to do with his retirement shortly thereafter. My mentor who'd worked at Cold Spring Harbor, well I won't quote her, but her comments support the Asshole theory of Watson.
Still he is Watson of the Watson strand of DNA (the other is named for Crick). And He, like Venter are rock star scientists. I’d totally take my picture with them making faux gansta signs and post them to facebook if they universe is ever kind enough to give me that opportunity. I’ll tell you more about Venter in a second. Incidentally, Watson hates Venter and called him “Hitler”.
2. Altschul et al’s Basic Local Alignment Search Tool (BLAST) was the most cited paper in the 90’s. Everyone in bioinformatics recognizes the name of accidental first author Stephen Altshul, who got his position by virtue of alphabetical precedence. BLAST was the brainchild of last author David Lipman, the Director of the National Center for Biotechnology Information (NCBI) since 1989. Lipman is a trained physician with absolutely no drama in his wikipedia entry and obviously leads a distinguished career.
So what is this BLAST? Well, like “google”, “BLAST” is a verb with ubiquitous usage. I got taught how to BLAST as an undergrad and I bet children in high school and perhaps grade school are now BLASTing their names for fun.1 To BLAST is to identify variants of your nucleotide (or protein) sequence across all (sequenced) domains of life. (Damn that sampling bias.) Since we DNA-based life are remarkably similar metabolically, it’s possible to make a strong guess on the function of genes based on knowledge of another version of that gene in another organism. Not everything transfers over, but it’s somewhere to start.
Lipman and his team crafted the algorithm so that it could run efficiently. Progressive alignment, BLAST’s precurser, was too inefficient for the wealth of sequence data available at the time. Unlike earlier alignment programs, BLAST’s approach doesn’t perform exhaustive calculations to determine the absolute best answer to any sequence alignment problem it’s given. Instead it finds you solutions that are not significantly different from perfect. Which is all you needed anyway. Almost twenty years later, BLAST remains a cornerstone tool of bioinformaticians.
3. In the early 90’s, we’d begun sequencing whole genomes of viruses. Since sequencing reactions may only capture fragments of the genome, assembly of fragments becomes nontrivial. At first, the genome sequencing progressed by the primer-walking method where the genome is sequenced systematically from end to end. Primers for the next bit of sequence are chosen from the ends of the last sequence. Then came the shotgun method. Nice name eh? It’s a characterization of the approach. Forget primer walking. Let’s just sequence a bunch of this stuff randomly and then have a computer knit it all together. It sure worked for viruses. Bacteria however, have much larger genomes. The assembly problem gets orders of magnitude worse.
Venter’s paper “Whole Genome Random Sequencing and Assembly of Haemophilus influenxae Rd” is a classic, not simply because it describes the first complete genome of a free living organism, but it describes their solution to the assembly problem of shotgun sequencing.
Whew…. I think that’s a good first draft to build on. Pardon me as I read a bit more and edit. Draft 2 will be coming up in a few hours.
1. -Well, a few anyway. Go here, enter your name in the big box to find your totem. (I’m Candidatus Methanoregula boonei 6A8, an Archea. Archea are the ultimate outgroup. Interesting… ) .