Software created at Washington University School of Medicine in St. Louis can forecast what will happen to intricate gene networks when specific genes are absent or turned up more than usual. These genetic networks are crucial for early embryonic development because they direct stem cells to differentiate into particular cell types that later grow into tissues and organs.
Understanding healthy development and figuring out how to repair damaged cells and tissues depends on mapping the roles of individual genes in these networks. Similarly to this, comprehending genetic mistakes may shed light on cancer, miscarriage, and birth deformities.
Since many years ago, developmental biology research has been heavily reliant on these kinds of genetic tests, which are normally carried out in laboratories using animal models like mice and zebrafish. Animal studies in which a gene is absent or overexpressed can teach us a lot about a gene’s function, but these tests are also costly and time-consuming.
In contrast, the newly developed software called CellOracle described Feb. 8 in the journal Nature can model hundreds of genetic experiments in a matter of minutes, helping scientists identify key genes that play important roles in development but that may have been missed by older, slower techniques. CellOracle is open source, with the code and information about the software available at this link.
“The scientific community has collected enough data from animal experiments that we now can do more than observe biology happening we can build computer models of how genes interact with each other and predict what will happen when one gene is missing,” said senior author Samantha A. Morris, PhD, an associate professor of developmental biology and of genetics.
“And we can do this without any experimental intervention. Once we identify an important gene, we still need to do the lab experiments to verify the finding. But this computational method helps scientists narrow down which genes are most important.”
We found that if we dialed up two specific genes, we can transform skin cells into a type of cell that can repair damaged intestine and liver. In terms of regenerative medicine, these predictive tools are valuable in modeling how we can reprogram cells into becoming the types of cells that can promote healing after injury or disease.
Samantha A. Morris
One of a number of relatively recent software systems created to model insights into cellular gene control is CellOracle, which was mentioned in a recent technology article in the journal Nature.
CellOracle is special in that it enables researchers to test out what occurs when a network is disrupted in a certain way, rather than just identifying the networks.
To demonstrate that CellOracle functions effectively, Morris and her team took advantage of well-known developmental processes such as blood cell production in mice and humans and embryonic development in zebrafish.
Their studies, in collaboration with the lab of co-author and zebrafish development expert Lilianna Solnica-Krezel, PhD, the Alan A. and Edith L. Wolff Distinguished Professor and head of the Department of Developmental Biology, also uncovered new roles for certain genes in zebrafish development that had not previously been identified.
And in a related paper online in the journal Stem Cell Reports, Morris and her colleagues used CellOracle to predict what happens when certain genes are dialed up beyond their usual expression levels.
“We found that if we dialed up two specific genes, we can transform skin cells into a type of cell that can repair damaged intestine and liver,” Morris said. “In terms of regenerative medicine, these predictive tools are valuable in modeling how we can reprogram cells into becoming the types of cells that can promote healing after injury or disease.”
Morris asserts that the majority of laboratory techniques used to transform stem cells into various cell types, such as liver or blood cells, are ineffective. Maybe 2% of the cells arrive at the desired destination.
Scientists can determine what ingredients should be added to the cocktail to steer more cells toward the target cell type, such as those capable of mending the gut and liver, with the aid of tools like CellOracle.
At present, CellOracle can model cell identity in more than 10 different species, including humans, mice, zebrafish, yeast, chickens, Guinea pigs, rats, fruit flies, roundworms, the Arabidopsis plant and two species of frog.
“We get a lot of requests to add different species,” Morris said. “We’re working on adding axolotl, which is a type of salamander. They are cool animals for studying regeneration because of their ability to regrow entire limbs and other complex organs and tissues.”
