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Reduced activity of two genes in combination often has a more detrimental effect than expected. Such epistatic interactions not only occur when genes are mutated but also due to variation in gene expression, including among isogenic individuals in a controlled environment. We hypothesized that these 'epigenetic' epistatic interactions could place important(More)
PDZ domain-mediated interactions have greatly expanded during metazoan evolution, becoming important for controlling signal flow via the assembly of multiple signaling components. The evolutionary history of PDZ domain-mediated interactions has never been explored at the molecular level. It is of great interest to understand how PDZ domain-ligand(More)
Characterizing the subcellular localization of a protein provides a key clue for understanding protein function. However, different protein localization prediction programs often deliver conflicting results regarding the localization of the same protein. As the number of available localization prediction programs continues to grow, there is a need for a(More)
Proteins targeting the same subcellular localization tend to participate in mutual protein-protein interactions (PPIs) and are often functionally associated. Here, we investigated the relationship between disease-associated proteins and their subcellular localizations, based on the assumption that protein pairs associated with phenotypically similar(More)
Various mammalian cells including tumor cells secrete extracellular vesicles (EVs), otherwise known as exosomes and microvesicles. EVs are nanosized bilayered proteolipids and play multiple roles in intercellular communication. Although many vesicular proteins have been identified, their functional interrelationships and the mechanisms of EV biogenesis(More)
Cancers, like many diseases, are normally caused by combinations of genetic alterations rather than by changes affecting single genes. It is well established that the genetic alterations that drive cancer often interact epistatically, having greater or weaker consequences in combination than expected from their individual effects. In a stringent statistical(More)
Successful viral infection requires intimate communication between virus and host cell, a process that absolutely requires various host proteins. However, current efforts to discover novel host proteins as therapeutic targets for viral infection are difficult. Here, we developed an integrative-genomics approach to predict human genes involved in the early(More)
Characterizing the spatial organization of the human mitochondrial proteome will enhance our understanding of mitochondrial functions at the molecular level and provide key insight into protein-disease associations. However, the sub-organellar location and possible association with mitochondrial diseases are not annotated for most mitochondrial proteins.(More)
The extent to which evolutionary changes have impacted the phenotypic relationships among human diseases remains unclear. In this work, we report that phenotypically similar diseases are connected by the evolutionary constraints on human disease genes. Human disease groups can be classified into slowly or rapidly evolving classes, where the diseases in the(More)
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