CRISPR Gene Editing Links Genes to Their Functions
Scientists led by MIT have published the first comprehensive functional map of genes that are expressed in human cells. The map ties each gene to its job in the cell.
A research paper is published in Cell. It reports that the scientists used the Perturb-seq method. This method uses CRISPR-Cas9 genome editing to introduce genetic changes into cells. It then analyzes the results to decode the many cellular effects of genetic changes.
The idea behind Perturb-seq is pretty simple, explains SingularityHub. “Imagine a toddler breaking stuff and realizing what he’s done after seeing the consequences. Perturb-seq uses CRISPR-Cas9 to silence multiple genes at once, which may sometimes change a cell’s behavior.”
Using human blood cancer cell lines as well as noncancerous cells derived from the retina, the scientists performed Perturb-seq across more than 2.5 million cells. And they used the data to build a comprehensive map. It ties genotypes (genetic material of an organism) to phenotypes (observable characteristics of an organism).
SingularityHub compares the map to “a Rosetta Stone for translating genotypes to phenotypes, with the help of CRISPR.” The map has been made available to other scientists as a database to build upon.
“It’s a big resource in the way the human genome is a big resource, in that you can go in and do discovery-based research,” says research co-leader Jonathan Weissman in a press release issued by MIT. “I think this dataset is going to enable all sorts of analyses that we haven't even thought up yet by people who come from other parts of biology, and suddenly they just have this available to draw on,” adds research co-leader Tom Norman.
“The advantage of Perturb-seq is it lets you get a big dataset in an unbiased way,” says Norman. “No one knows entirely what the limits are of what you can get out of that kind of dataset. Now, the question is, what do you actually do with it?”
One application is to look into genes with unknown functions. Scientists can use the data to compare unknown genes to known ones and look for similarities.
Another application is to study complex phenotypes. “We often take all the cells where ‘gene X’ is knocked down and average them together to look at how they changed,” explains Weissman. “But sometimes when you knock down a gene, different cells that are losing that same gene behave differently, and that behavior may be missed by the average.”
The scientists plan to use Perturb-seq on different types of cells besides the cancer cell line with which they started. They also plan to continue to explore their map of gene functions. And they hope others will do the same.
“This really is the culmination of many years of work by the authors and other collaborators, and I’m really pleased to see it continue to succeed and expand,” concludes Norman.
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