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August 25, 2020
Members of the Yaffe group have been developing computational methods to examine RNA-binding proteins as a class of molecules that might broadly be involved in how tumors respond to chemotherapy. Alterations in the function of these proteins, caused by various stimuli including therapeutics, contribute to changes in gene expression, but identifying which proteins are responsible for a given change remains challenging. In a Cell Reports paper, the researchers describe a computer program they developed called Transite, which systematically infers which RNA-binding proteins are influencing gene expression through changes in RNA stability and degradation. The versatile tool allows users to identify key RNA-binding proteins from gene expression datasets, be they publicly available or results from any experiment that measures the expression levels of large numbers of genes simultaneously, such as RNA sequencing.
In a proof of principle study, the Yaffe lab applied Transite to RNA expression data from human patients with non-small-cell lung cancer whose tumors were sampled at diagnosis or after recurrence following chemotherapy. Transite implicated known RNA-binding proteins regulators of the DNA damage response—many chemotherapies work by damaging a cancer cell’s DNA—and also identified the protein hnRNPC as a new modulator of chemotherapy resistance, which the Yaffe group validated experimentally. This work builds on previous studies in the lab that identified a clinically relevant role in lung cancer for another member of the same family of RNA-binding proteins, hnRNPA0.
The Yaffe laboratory has made Transite broadly available to the entire scientific community online at https://transite.mit.edu. To date, it has already been used to perform hundreds of analyses.
This work was supported in part by the MIT Center for Precision Cancer Medicine and the Charles and Marjorie Holloway Foundation.