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Question for anyone working with CRISPR... What's the current state of the art for using computers to model or simulate how a gene change will impact the rest

Question for anyone working with CRISPR... What's the current state of the art for using computers to model or simulate how a gene change will impact the rest of an organism? Separate but related, if you were to collect data on that sort of thing during an experiment, how would you? I assume there's quite a bit of variation depending on experiment goal... Is imaging technology to the point where you can record what happens as video?

scottish-alien 11y ago
Your questions aren't specific for people working with CRISPR, but more generally relate to gene-editing. Unfortunately, molecular biology and genetics are immensely complex, once you start looking in to them. There very rarely is a 1:1 correlation between one gene and one single function of impact on the entire organism (even for single celled organisms). Moreover, in many cases loss of one gene can be compensated by the function of one or multiple different protein(s). To be fair, I haven't looked up any literature on computer models of how the change of one a single gene would influence the whole organism. However, that is a very complicated question. The closest analogy I can give you is "are there computer models how changing a resistor/capacitor will impact the quality of the picture of my TV?" Frankly, it's often hard to tell how the (novel) change of a single gene will influence a single cell! Regarding your second question: the data you want to collect is always related to the question your asking about the gene at hand. "How does loss of gene X impact cognitive capacity" would obviously require a completely different experimental set-up than asking "Which functional role does gene X fulfil in the immune system". Sorry I can't give a more satisfying answer. On a slightly related note, this article gives some insight on how biologists think and go about their experimental design and recording what they learn: http://math.arizona.edu/~jwatkins/canabiologistfixaradio.pdf http://math.arizona.edu/~jwatkins/canabiologistfixaradio.pdf
pak 11y ago
This is actually something one of my thesis committee members worked on. http://www.cell.com/abstract/S0092-8674(12)00776-3 http://www.cell.com/abstract/S0092-8674(12)00776-3 In silico whole cell models are an extremely new concept, and his study demonstrated its capabilities for one small bacterium. Needless to say, we have a long way to go before we can make top-down simulations of multicellular organisms, much less one as complex as a human. There are many people trying to generate "good enough" simulations for certain human diseases though, by modeling interactions between genes and biomolecules among a few tissues within the relevant organ system. With regard to your second question, there are many "omics" assays that can now capture e.g. every mRNA, every protein, etc. at a given timepoint but you have to kill the cells. Fluorescence microscopy can work for "movie-like" time resolution on a live cell but you have to label the cellular elements with stains or antibodies and you can only utilize so many of those simultaneously on a single sample (1-5 is typical).
- ccvannorman 11y ago
  >There are many people trying to generate "good enough" simulations Who? As a 3D software engineer moving into this space, this is extremely relevant to me. :-]
  - pak 11y ago
    Pretty much anything in the "network biology" field will likely interest you, but here are a few sample articles (heavily biased toward people that I currently work with): http://www.ncbi.nlm.nih.gov/pubmed/18344982 http://www.ncbi.nlm.nih.gov/pubmed/18344982 http://www.ncbi.nlm.nih.gov/pubmed/19337271 http://www.ncbi.nlm.nih.gov/pubmed/19337271 http://www.ncbi.nlm.nih.gov/pubmed/18462017 http://www.ncbi.nlm.nih.gov/pubmed/18462017

scottish-alien 11y ago

Your questions aren't specific for people working with CRISPR, but more generally relate to gene-editing. Unfortunately, molecular biology and genetics are immensely complex, once you start looking in to them. There very rarely is a 1:1 correlation between one gene and one single function of impact on the entire organism (even for single celled organisms). Moreover, in many cases loss of one gene can be compensated by the function of one or multiple different protein(s). To be fair, I haven't looked up any literature on computer models of how the change of one a single gene would influence the whole organism. However, that is a very complicated question. The closest analogy I can give you is "are there computer models how changing a resistor/capacitor will impact the quality of the picture of my TV?" Frankly, it's often hard to tell how the (novel) change of a single gene will influence a single cell! Regarding your second question: the data you want to collect is always related to the question your asking about the gene at hand. "How does loss of gene X impact cognitive capacity" would obviously require a completely different experimental set-up than asking "Which functional role does gene X fulfil in the immune system". Sorry I can't give a more satisfying answer. On a slightly related note, this article gives some insight on how biologists think and go about their experimental design and recording what they learn: http://math.arizona.edu/~jwatkins/canabiologistfixaradio.pdf http://math.arizona.edu/~jwatkins/canabiologistfixaradio.pdf

pak 11y ago

This is actually something one of my thesis committee members worked on. http://www.cell.com/abstract/S0092-8674(12)00776-3 http://www.cell.com/abstract/S0092-8674(12)00776-3 In silico whole cell models are an extremely new concept, and his study demonstrated its capabilities for one small bacterium. Needless to say, we have a long way to go before we can make top-down simulations of multicellular organisms, much less one as complex as a human. There are many people trying to generate "good enough" simulations for certain human diseases though, by modeling interactions between genes and biomolecules among a few tissues within the relevant organ system. With regard to your second question, there are many "omics" assays that can now capture e.g. every mRNA, every protein, etc. at a given timepoint but you have to kill the cells. Fluorescence microscopy can work for "movie-like" time resolution on a live cell but you have to label the cellular elements with stains or antibodies and you can only utilize so many of those simultaneously on a single sample (1-5 is typical).

ccvannorman 11y ago
>There are many people trying to generate "good enough" simulations Who? As a 3D software engineer moving into this space, this is extremely relevant to me. :-]
- pak 11y ago
  Pretty much anything in the "network biology" field will likely interest you, but here are a few sample articles (heavily biased toward people that I currently work with): http://www.ncbi.nlm.nih.gov/pubmed/18344982 http://www.ncbi.nlm.nih.gov/pubmed/18344982 http://www.ncbi.nlm.nih.gov/pubmed/19337271 http://www.ncbi.nlm.nih.gov/pubmed/19337271 http://www.ncbi.nlm.nih.gov/pubmed/18462017 http://www.ncbi.nlm.nih.gov/pubmed/18462017