MSGID: 1:317/3 63e719f6   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Computer model IDs roles of individual genes in early embryonic   
   development    
    May provide insight into birth defects, miscarriage, cancer    
      
     Date:   
         February 10, 2023   
     Source:   
         Washington University School of Medicine   
     Summary:   
         Computer software can predict what happens to complex gene   
         networks when individual genes are missing or dialed up more than   
         usual. Mapping the roles of single genes in these networks is key   
         to understanding healthy development and finding ways to regrow   
         damaged cells and tissues.   
      
         Understanding genetic errors could provide insight into birth   
         defects, miscarriage or even cancer.   
      
      
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   FULL STORY   
   ==========================================================================   
   Computer software developed at Washington University School of Medicine   
   in St.   
      
   Louis can predict what happens to complex gene networks when individual   
   genes are missing or dialed up more than usual. Such genetic networks   
   play key roles in early embryonic development, guiding stem cells to   
   form specific cell types that then build tissues and organs. Mapping   
   the roles of single genes in these networks is key to understanding   
   healthy development and finding ways to regrow damaged cells and   
   tissues. Likewise, understanding genetic errors could provide insight   
   into birth defects, miscarriage or even cancer.   
      
      
   ==========================================================================   
   Such genetic experiments -- typically conducted in the laboratory   
   in animal models such as mice and zebrafish -- have been a mainstay   
   of developmental biology research for decades. Much can be learned   
   about a gene's function in animal studies in which a gene is missing   
   or overexpressed, but these experiments are also expensive 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 thislink.   
      
   "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."  CellOracle,   
   which was included in a recent technology feature in the journal Nature,   
   is one of a number of relatively new software systems designed to model   
   insights into cellular gene regulation. Rather than simply identify the   
   networks, CellOracle is unique in its ability to let researchers test   
   out what happens when a network is disrupted in a specific way.   
      
   Morris and her team harnessed the well-known developmental processes of   
   blood cell formation in mice and humans and embryonic development in   
   zebrafish to validate that CellOracle works properly. 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."  According to Morris,   
   most laboratory methods for converting stem cells into different cell   
   types, such as blood cells or liver cells, are inefficient.   
      
   Maybe 2% of the cells arrive at the desired destination. Tools like   
   CellOracle can help scientist identify what factors should be added to   
   the cocktail to guide more cells into the desired cell type, such as   
   those capable repairing the gut and liver.   
      
   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."   
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Stem_Cells # Genes # Brain_Tumor   
             o Plants_&_Animals   
                   # Developmental_Biology # Genetics # Biotechnology   
             o Computers_&_Math   
                   # Computer_Modeling # Software # Computer_Programming   
       * RELATED_TERMS   
             o BRCA1 o BRCA2 o Cancer o Gene_therapy o Gene o   
             Introduction_to_genetics o Genetic_code o Human_genome   
      
   ==========================================================================   
   Story Source: Materials provided by   
   Washington_University_School_of_Medicine. Original written by Julia   
   Evangelou Strait. Note: Content may be edited for style and length.   
      
      
   ==========================================================================   
   Journal References:   
      1. Kenji Kamimoto, Blerta Stringa, Christy M. Hoffmann, Kunal Jindal,   
         Lilianna Solnica-Krezel, Samantha A. Morris. Dissecting   
         cell identity via network inference and in silico gene   
         perturbation. Nature, 2023; DOI: 10.1038/s41586-022-05688-9   
      2. Kenji Kamimoto, Mohd Tayyab Adil, Kunal Jindal, Christy M. Hoffmann,   
         Wenjun Kong, Xue Yang, Samantha A. Morris. Gene regulatory network   
         reconfiguration in direct lineage reprogramming. Stem Cell Reports,   
         2023; 18 (1): 97 DOI: 10.1016/j.stemcr.2022.11.010   
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   Link to news story:   
   https://www.sciencedaily.com/releases/2023/02/230210185147.htm   
      
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