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Related Experiment Videos

The human disease network.

Kwang-Il Goh1, Michael E Cusick, David Valle

  • 1Center for Complex Network Research and Department of Physics, University of Notre Dame, Notre Dame, IN 46556, USA.

Proceedings of the National Academy of Sciences of the United States of America
|May 16, 2007
PubMed
Summary
This summary is machine-generated.

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This study reveals that most disease genes are nonessential and located on the network periphery, unlike essential genes which are central hubs. This finding helps explain disease origins and somatic mutation effects in cancer.

Area of Science:

  • Genomics
  • Systems Biology
  • Bioinformatics

Background:

  • A network of known disorder-gene associations provides a framework to study disease origins.
  • Genes linked to similar disorders exhibit functional similarities, suggesting distinct disease-specific modules.

Purpose of the Study:

  • To explore the genetic origins of diseases using a graph-theoretic framework.
  • To differentiate the network properties of essential genes versus disease genes.
  • To investigate the localization and characteristics of disease-associated genes within the human interactome.

Main Methods:

  • Graph theory and network analysis of disorder-gene associations.
  • Analysis of gene product physical interactions and transcript expression profiles.
  • Comparison of network properties (e.g., essentiality, hub status, expression patterns) between essential and disease genes.

Related Experiment Videos

  • Development and testing of a selection-based model for gene evolution and disease association.

    • Main Results:

    • Essential human genes are typically central hub proteins with widespread tissue expression.
    • Most disease genes are nonessential, located in the network periphery, and do not encode hub proteins.
    • A selection-based model explains the peripheral nature of most disease genes and predicts that somatic mutation-driven diseases (e.g., cancer) involve non-peripheral genes, a prediction confirmed for cancer genes.

    Conclusions:

    • Disease genes often reside in the functional periphery of the human interactome, contrasting with essential genes.
    • The study provides insights into the common genetic origins of diseases and the distinct network roles of essential versus disease-associated genes.
    • The findings support a model where somatic mutations driving diseases like cancer involve genes with different network characteristics than those causing inherited disorders.