“The exciting discovery was that isoforms coming from the same gene often interacted with different protein partners,” study coauthor Gloria Sheynkman of the Dana-Farber Cancer Institute said in astatement. “This suggests that the isoforms play very different roles within the cell.”

Unlike previous functional studies of isoforms, which have generally focused on one or a handful of genes, this project systematically analyzed the interactions of multiple isoforms from hundreds of genes.

The researchers found that, on average, two related isoforms shared less than 50 percent of interacting proteins; 16 percent of related isoforms shared none at all. These differences in interaction partners were often associated with only tiny alterations in DNA sequence—sometimes just a single base pair.

“From the perspective of all the protein interactions within a cell, related isoforms behave more like distinct proteins than minor variants of one another,” study coauthor Tong Hao of Dana-Farber said in the statement.

“A more detailed view at protein interaction networks, as presented in our paper, is especially important in relation to human diseases,” added study coauthor Lilia Iakoucheva of the University of California, San Diego. “Drastic differences in interaction partners among splicing isoforms strongly suggest that identification of the disease-relevant pathways at the gene level is not sufficient. . . . It’s time to take a deeper dive into the networks that we are building and analyzing.”