2019 Articles

Detailed prediction of protein sub-nuclear localization

Littmann, Maria; Goldberg, Tatyana; Seitz, Sebastian; Bodén, Mikael; Rost, Burkhard

Background
Sub-nuclear structures or locations are associated with various nuclear processes. Proteins localized in these substructures are important to understand the interior nuclear mechanisms. Despite advances in high-throughput methods, experimental protein annotations remain limited. Predictions of cellular compartments have become very accurate, largely at the expense of leaving out substructures inside the nucleus making a fine-grained analysis impossible.


Results
Here, we present a new method (LocNuclei) that predicts nuclear substructures from sequence alone. LocNuclei used a string-based Profile Kernel with Support Vector Machines (SVMs). It distinguishes sub-nuclear localization in 13 distinct substructures and distinguishes between nuclear proteins confined to the nucleus and those that are also native to other compartments (traveler proteins). High performance was achieved by implicitly leveraging a large biological knowledge-base in creating predictions by homology-based inference through BLAST. Using this approach, the performance reached AUC = 0.70–0.74 and Q13 = 59–65%. Travelling proteins (nucleus and other) were identified at Q2 = 70–74%. A Gene Ontology (GO) analysis of the enrichment of biological processes revealed that the predicted sub-nuclear compartments matched the expected functionality. Analysis of protein-protein interactions (PPI) show that formation of compartments and functionality of proteins in these compartments highly rely on interactions between proteins. This suggested that the LocNuclei predictions carry important information about function. The source code and data sets are available through GitHub:
https://github.com/Rostlab/LocNuclei

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Conclusions
LocNuclei predicts subnuclear compartments and traveler proteins accurately. These predictions carry important information about functionality and PPIs.