3 ms·

A lot more information is needed to understand the genome than just the linear sequence or 3D structure. There is phosphorylation and histone tags and RNA splic

by jostmey 14y ago

A lot more information is needed to understand the genome than just the linear sequence or 3D structure. There is phosphorylation and histone tags and RNA splicing and more (and that's just what has been discovered). All this information is needed to understand how the genome works. It is basic genetics.

ChuckMcM 14y ago
"It is basic genetics." According to the NYT [1] it's 'new' basic genetics. Basically all the 'junk' DNA isn't junk, and the reason the function of that DNA was not appreciated before the ENCODE effort is that these bits appeared 'far away' from the genes which it turns out they affect. [1] "There is another sort of hairball as well: the complex three-dimensional structure of DNA. Human DNA is such a long strand — about 10 feet of DNA stuffed into a microscopic nucleus of a cell — that it fits only because it is tightly wound and coiled around itself. When they looked at the three-dimensional structure — the hairball — Encode researchers discovered that small segments of dark-matter DNA are often quite close to genes they control. In the past, when they analyzed only the uncoiled length of DNA, those controlling regions appeared to be far from the genes they affect." http://www.nytimes.com/2012/09/06/science/far-from-junk-dna-dark-matter-proves-crucial-to-health.html?_r=1&pagewanted=all http://www.nytimes.com/2012/09/06/science/far-from-junk-dna-...
- jostmey 14y ago
  Obviously the 3D structure of chromosomes are important. But it is only one of many aspects that regulate our genes. While it is true we cannot understand the genome by ignoring its 3D shape, we also cannot understand the genome without looking at the many other ways the genome is regulated. Nature did not make things simple for us. There are quite a few variables that regulate our genes, and sadly it seems that all or most of these variables must be taken into account
- east2west 14y ago
  If you knew how they found the elements together, you would be far less sanguine about the significance. They started with random sampling of close proximity of genomic positions, plus some basic structural info on how chromatins (coiled DNA molecular) are organized. Then it is a nonlinear optimization with 1e-2 convergence criteria. Several things lay people are never told: 1. Even for fixed data, the results are variable, i.e., you will get a different answer every time you run the nonlinear programming code. 2. There are different ways of getting to 3D positions of genomes and none is ever verified. 3. Tuning parameters greatly impact results. Yet one set of tuning parameters are just as valid as another. I had the misfortune of helping someone to extend the code for this stuff that made into a Science paper, and I can tell you right now it is the worst C++ program I have ever seen.

by jostmey 14y ago

ChuckMcM 14y ago

"It is basic genetics." According to the NYT [1] it's 'new' basic genetics. Basically all the 'junk' DNA isn't junk, and the reason the function of that DNA was not appreciated before the ENCODE effort is that these bits appeared 'far away' from the genes which it turns out they affect. [1] "There is another sort of hairball as well: the complex three-dimensional structure of DNA. Human DNA is such a long strand — about 10 feet of DNA stuffed into a microscopic nucleus of a cell — that it fits only because it is tightly wound and coiled around itself. When they looked at the three-dimensional structure — the hairball — Encode researchers discovered that small segments of dark-matter DNA are often quite close to genes they control. In the past, when they analyzed only the uncoiled length of DNA, those controlling regions appeared to be far from the genes they affect." http://www.nytimes.com/2012/09/06/science/far-from-junk-dna-dark-matter-proves-crucial-to-health.html?_r=1&pagewanted=all http://www.nytimes.com/2012/09/06/science/far-from-junk-dna-...

jostmey 14y ago
Obviously the 3D structure of chromosomes are important. But it is only one of many aspects that regulate our genes. While it is true we cannot understand the genome by ignoring its 3D shape, we also cannot understand the genome without looking at the many other ways the genome is regulated. Nature did not make things simple for us. There are quite a few variables that regulate our genes, and sadly it seems that all or most of these variables must be taken into account
east2west 14y ago
If you knew how they found the elements together, you would be far less sanguine about the significance. They started with random sampling of close proximity of genomic positions, plus some basic structural info on how chromatins (coiled DNA molecular) are organized. Then it is a nonlinear optimization with 1e-2 convergence criteria. Several things lay people are never told: 1. Even for fixed data, the results are variable, i.e., you will get a different answer every time you run the nonlinear programming code. 2. There are different ways of getting to 3D positions of genomes and none is ever verified. 3. Tuning parameters greatly impact results. Yet one set of tuning parameters are just as valid as another. I had the misfortune of helping someone to extend the code for this stuff that made into a Science paper, and I can tell you right now it is the worst C++ program I have ever seen.