Abstract

Eukaryotic cells contain numerous components, which are known as subcellular compartments or subcellular organelles. Proteins must be sorted to proper subcellular compartments to carry out their molecular functions. Mis-localized proteins are related to various cancers. Identifying mis-localized proteins is important in understanding the pathology of cancers and in developing therapies. However, experimental methods, which are used to determine protein subcellular locations, are always costly and time-consuming. We tried to identify cancer-related mis-localized proteins in three different cancers using computational approaches. By integrating gene expression profiles and dynamic protein-protein interaction networks, we established DPPN-SVM (Dynamic Protein-Protein Network with Support Vector Machine), a predictive model using the SVM classifier with diffusion kernels. With this predictive model, we identified a number of mis-localized proteins. Since we introduced the dynamic protein-protein network, which has never been considered in existing works, our model is capable of identifying more mis-localized proteins than existing studies. As far as we know, this is the first study to incorporate dynamic protein-protein interaction network in identifying mis-localized proteins in cancers.

Highlights

  • Eukaryotic cell is the most basic structural and functional unit of eukaryotic living creatures

  • We developed a mis-localization score, which describes how likely a protein will move to or leave from a specific subcellular location in a specific cellular condition

  • All other types of interactions were removed. This is because the physical interactions implied that the two interactors have a very short physical distance, which contributes to protein subcellular location predictions

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Summary

Introduction

Eukaryotic cell is the most basic structural and functional unit of eukaryotic living creatures. Proteins, which are translated in cytosol or rough ER (Endoplasmic Reticulum), must be transported to proper compartments during or after the translations to perform their biological functions (Mitra et al, 2006; Nyathi et al, 2013; Johnson et al, 2013). This process is known as the protein sorting process (Alberts et al, 2002). The subcellular organelles, where a protein performs its biological functions, are called the subcellular localization of the protein. Tracking alternative subcellular locations in different cellular conditions is important in understanding the pathology of complex diseases, like cancers

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