UVA researcher Jason Papin and colleagues have created a sophisticated new computer model of male and female livers that will make for safer drugs with fewer side effects. Credit: Dan Addison | UVA Communications
Key points:
- Researchers have created liver computer simulations to examine sex-specific differences in the response to drugs.
- Using the computer model, the research team identified a series of cellular processes that explain sex differences in liver damage.
- Predictive computer models of complex biological systems, including the liver, are crucial for the development of safer drugs for men and women.
While women experience a disproportionate number of liver problems from medications, they are underrepresented in drug testing. To investigate how medications affect men and women differently, a team of scientists developed computer simulations of livers and used them to examine sex-specific differences in the response to drugs.
The computer model, published in PLOS Computational Biology, integrates large amounts of data on gene activity and metabolic processes. The models of male and female livers provide unprecedented insights into the liver’s biological processes and act as a powerful tool for drug development to ensure new medications do not have harmful side effects.
“There are incredibly complex networks of genes and proteins that control how cells respond to drugs,” said Jason Papin, one of the model’s creators. “We knew that a computer model would be required to try to answer these important clinical questions, and we’re hopeful these models will continue to provide insights that can improve healthcare.”
Due to the complexity of drug therapy for the liver and the potential for toxicity, ensuring the proper dosing for both men and women is imperative. Researchers analyzed the Food and Drug Administration’s Adverse Event Reporting System and discovered that women consistently report liver-related adverse events more frequently than men. Using their model, the research team identified a series of cellular processes that explain these sex differences in liver damage.
“We were surprised how many differences we found, especially in very diverse biochemical pathways,” said Connor Moore of Papin’s lab at University of Virginia. “We hope our results emphasize how important it is for future scientists to consider how both men and women are affected by their research.”
Looking ahead, researchers aim to investigate sex differences underlying hepatotoxicity and use this information to develop safer drugs for both sexes. Predictive computer models of complex biological systems, as demonstrated in this study, can identify new targets and therapeutic pathways in even the most challenging biomedical problems.