New data integration method deciphers RAS oncoprotein functions
In a world where we are inundated by data, putting them together for deeper understanding has become a grand challenge. Researchers at Systems Biology Ireland (SBI) have developed a new method for integrating and analysing different types of molecular cancer data in order to disrupt the signaling systems of cancer-causing RAS proteins, according to a study published this week in Cell Reports.
In a paper titled “An integrated global analysis of compartmentalized HRAS signaling,” SBI researchers present a conceptual framework called MiNETi (Mixed Network Integration) that can integrate many different types of molecular data, such as protein interactions, phosphoproteomics and transcriptomics data. This method is particularly novel because these data have, before now, been analysed separately as they are notoriously difficult to combine. MiNETi combines existing knowledge and empirical rules on connections between biochemical and biological processes within a statistical framework to integrate networks.
Professor Walter Kolch, corresponding author of the study, said: “The big step forward is that we can now integrate any type of data that can be displayed as a network, including highly complex molecular data, using intuitive rules. This enables us to understand very complicated relationships and make predictions about the behaviour of the whole system rather than individual parts”
The study applied MiNETi to decipher the functions of the RAS oncoprotein.
Kolch explained: “Activating RAS mutations are found in 20 – 30 percent of human cancers, including colorectal, lung and pancreatic cancers. These are particularly nasty as they typically provide a poor prognosis with little-to-no therapy or drugs available to work against them. RAS can also be found in different places in the cell and behave differently depending on where it is.”
Using MiNETi, the researchers found that the HRAS oncoprotein signals from different subcellular compartments to control biological processes that subvert normal cells to cancer cells. A unique bonus in this study was the discovery of unexpected RAS functions including the control of cell migration from the endoplasmic reticulum. According to Kolch, this opens up the possibility for selecting specific features of RAS to disrupt, a strategy that could be beneficial in cancer treatments. According to the study, an important characteristic of the integrated network is that it provides a more coherent picture of molecular events triggered by HRAS than was possible before by any individual -omic screen. Having a clearer picture of the events could lead to future breakthroughs in treating difficult forms of cancer.
“An integrated global analysis of compartmentalized HRAS signaling” Cell Reports 2019
DOI: https://doi.org/10.1016/j.celrep.2019.02.038
