Marinka Zitnik

Fusing bits and DNA

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Bioinformatics: Orthogonal Factorization of RNA-Binding Proteins

Our paper on integrative analysis of multiple RNA-binding proteins has just appeared in Bioinformatics. RNA binding proteins (RBPs) are important for many cellular processes, including post-transcriptional control of gene expression, splicing, transport, polyadenylation and RNA stability. To better understand the RBP mechanisms we aimed to integrate the rapidly growing RBP experimental data with the latest genome annotation, gene function, RNA sequence and structure.

We have developed an integrative orthogonality-regularized nonnegative matrix factorization that can integrate multiple data sets and discover non-overlapping and class-specific RNA binding patterns of varying strengths. The orthogonality constraint is important here because it enables us to substantially reduce the effective size of inferred factor models.

The new models have proved powerful in predicting RBP interaction sites on RNA. We also showed that joint analysis of multiple data sets can boost retrieval accuracy of RNA binding sites, which we studied using the largest RBP data compendium to date.