Comparative Analysis of Human Tissue Interactomes Reveals Factors Leading to Tissue-Specific Manifestation of Hereditary Diseases

نویسندگان

  • Ruth Barshir
  • Omer Shwartz
  • Ilan Y. Smoly
  • Esti Yeger Lotem
چکیده

An open question in human genetics is what underlies the tissue-specific manifestation of hereditary diseases, which are caused by genomic aberrations that are present in cells across the human body. Here we analyzed this phenomenon for over 300 hereditary diseases by using comparative network analysis. We created an extensive resource of protein expression and interactions in 16 main human tissues, by integrating recent data of gene and protein expression across tissues with data of protein-protein interactions (PPIs). The resulting tissue interaction networks (interactomes) shared a large fraction of their proteins and PPIs, and only a small fraction of them were tissue-specific. Applying this resource to hereditary diseases, we first show that most of the disease-causing genes are widely expressed across tissues, yet, enigmatically, cause disease phenotypes in few tissues only. Upon testing for factors that could lead to tissue-specific vulnerability, we find that disease-causing genes tend to have elevated transcript levels and increased number of tissue-specific PPIs in their disease tissues compared to unaffected tissues. We demonstrate through several examples that these tissue-specific PPIs can highlight disease mechanisms, and thus, owing to their small number, provide a powerful filter for interrogating disease etiologies. As two thirds of the hereditary diseases are associated with these factors, comparative tissue analysis offers a meaningful and efficient framework for enhancing the understanding of the molecular basis of hereditary diseases.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

A convex optimization approach for identification of human tissue-specific interactomes

MOTIVATION Analysis of organism-specific interactomes has yielded novel insights into cellular function and coordination, understanding of pathology, and identification of markers and drug targets. Genes, however, can exhibit varying levels of cell type specificity in their expression, and their coordinated expression manifests in tissue-specific function and pathology. Tissue-specific/tissue-s...

متن کامل

Tissue Specific Expression of Human Calcitonin Gene in Potato Tubers by an Organ Specific Promoter

To increase the production level of heterologous proteins in plants, strategies such as choice of strongerpromoters, optimization of codon usage and specific localization of foreign proteins are of major concern.Calcitonin (CT), a 32 amino acid polypeptide is a powerful and specific inhibitor of bone resorption and isused to treat several human diseases. Calcitonin activity is...

متن کامل

Construction and Analysis of Tissue-Specific Protein-Protein Interaction Networks in Humans

We have studied the changes in protein-protein interaction network of 38 different tissues of the human body. 123 gene expression samples from these tissues were used to construct human protein-protein interaction network. This network is then pruned using the gene expression samples of each tissue to construct different protein-protein interaction networks corresponding to different studied ti...

متن کامل

Investigating the Factors Affecting the Mammographic Density of Breast Tissue in Patients Referred to the Breast Cancer Research Center, Iran

Introduction: Of the factors leading to false negative results in mammography is breast tissue density, and by increasing the density of breast tissue in mammography, the mammography sensitivity decreases. On the other hand, increasing the breast tissue density leads to increased risk of breast cancer. Various factors such as inheritance, genetics, hormonal and reproductive factors, and nutriti...

متن کامل

Investigating the Factors Affecting the Mammographic Density of Breast Tissue in Patients Referred to the Breast Cancer Research Center, Iran

Introduction: Of the factors leading to false negative results in mammography is breast tissue density, and by increasing the density of breast tissue in mammography, the mammography sensitivity decreases. On the other hand, increasing the breast tissue density leads to increased risk of breast cancer. Various factors such as inheritance, genetics, hormonal and reproductive factors, and nutriti...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 10  شماره 

صفحات  -

تاریخ انتشار 2014