The Human Genetic Disease Network

1. In 1999 Laszlo Barabási mapped the connectedness of the Web. To his surprise, the web did not have an even distribution of connectivity (so-called "random connectivity"). Instead, some network nodes had many more connections than the average; seeking a simple categorical label, Barabási called such highly connected nodes "hubs".

4. After finding that other networks, including some social and biological networks, also had similar node distributions, he coined the term "scale-free network" in which some nodes act as "highly connected hubs" (high degree), although most nodes are of low degree. Scale-free networks' structure and dynamics are independent of the system's size N, the number of nodes in a system. In other words, a network that is scale-free will have the same properties independent of the number of its nodes.

5. Barabási then offered a simple generative mechanism called "preferential attachment" (only physicists get away with this stuff) that created these non-random networks.

6. The Human Genetic Disease Network Kwang-Il Goh1,2,3, Michael E. Cusick2,4, David Valle5, Barton Childs5, Marc Vidal2,4 & Albert-László Barabási1,2 1Center for Complex Network Research and Department of Physics, University of Notre Dame, Notre Dame, IN 46556, USA 2Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, and 4Department of Genetics, Harvard Medical School, 44 Binney St., Boston, MA 02115, USA 3Department of Physics, Korea University, Seoul 136-713, Korea 5Department of Pediatrics and the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA

7. “To offer a global representation of the relationship between human diseases and disease genes, we introduce a network composed of disorders and disease genes linked by known disorder-gene associations. The obtained diseasome map connects most classes of disorders into a highly interlinked network, with strong local aggregation of disorders of similar type.” http://www.nd.edu/~kgoh/DISEASOME/

10. “We find that essential human gene products are likely to be hubs and are expressed widely in most tissues, suggesting that disease genes with severe phenotypes might also play a central role in the interactome. In contrast we observed that disease genes display the opposite trend, being localized in the cellular network’s functional periphery.”

13. “We predict that gene products associated with heritable diseases and essential proteins occupy fundamentally different positions in the global cellular network. By this model disease caused by somatic mutations should not be peripheral, a prediction confirmed for cancer genes.”

14. Radial Density Plot of the Diseasome The center corresponds to genes with high degree, high co-expression, and expressed in many tissues, representing the functional center o fthe cell, while the regions away from the center and the three axes represent the functional periphery of the cell.

15. “There are increasing efforts to understand the interplay between the environmental and genetic factors contributing to specific diseases. Once these efforts result in systematic datasets, cataloguing the specific environmental, disease and genetic links, our approach could be expanded to address the impact of the environment as well.”