9758

Hepatocellular Carcinoma Gene/Protein Networks

Hepatocellular carcinoma is considered the leading cause of death among people affected by hepatitis C virus-induced cirrhosis. This Demonstration integrates gene expressions from DNA microarrays with protein expressions from hepatocellular carcinoma and offers a global visualization of data currently available, suggesting an easy way to browse complex biological information and findings along the tumorigenesis development.

SNAPSHOTS

  • [Snapshot]
  • [Snapshot]
  • [Snapshot]

DETAILS

Background and Methods
Gene expressions were obtained from DNA microarrays produced by Elisa Wurmbach and collaborators [1]. The microarray is available at: http://www.ncbi.nlm.nih.gov/geo (GSE 6764) [2]. Gene expressions are clustered in seven observations that you can browse by means of the seven control buttons: (1) cirrhosis versus control ("Cirrhosis"); (2) low-grade nodules versus control ("LG-nodule"); (3) high-grade nodules versus control ("HG-nodule"); (4) very early cancer versus control ("Very Early"); (5) early cancer versus control ("Early"); (6) advanced cancer versus control ("Advanced"); and (7) very advanced cancer versus control ("Very Advanced").
Genes were defined as regulated when characterized by Student t test -values less than 0.01 in at least one observation. Statistics were performed by means of R bioconductor statistics programming environment (http://www.r-project.org) [3].
The dataset containing 11000 gene identifiers and corresponding expression values was then intersected with another dataset from protein expressions, produced by Tadashi Kondo [4], containing 21 proteomes from liver cancer.
After the genome/proteome intersection, a list of 290 annotated molecules was obtained and then uploaded into the Ingenuity Pathways Analysis application [5]. Each identifier was mapped to its corresponding object in Ingenuity's Knowledge Base. These molecules, called network-eligible molecules, were overlaid onto a global molecular network developed from information contained in Ingenuity's Knowledge Base. Networks of network-eligible molecules were then algorithmically generated based on their connectivity. The functional analysis of a network has identified the biological functions that were most significant to the molecules in the network. Only molecule networks associated with biological functions in Ingenuity's Knowledge Base were considered for the analysis.
Right-tailed Fisher's exact test was used to calculate a -value determining the probability that each biological function assigned to that network is due to chance alone. A total list of 16 networks from the 290 regulated genes was obtained. The Ingenuity System has added other molecules to obtain consistent networks. The total list of molecules present in this Demonstration is 529.
Each molecule within the 16 networks was then annotated considering the possible cell expression, by means of Biomart resources [6].
Instructions
1. After you have chosen which of the 16 networks (metabolism) you want to browse, you can visualize gene expressions, protein expressions, molecular functions, location, or biomarkers by means of the "view" control bar.
2. Gene and protein expressions are represented by two colors: red for upregulated molecules and green for downregulated molecules.
3. You can choose to represent molecules as simple disks or shapes corresponding to biological function.
4. Blurred disks/objects correspond to molecule regulations that are not statistically significant. You can also choose the disk size and the graph size.
5. You can choose to visualize text on disks, using the "text" check box. Names of molecules will be displayed on disks.
6. You can visualize directional arrows for each edge in networks using the "arrows" check box.
7. You can highlight molecules with biomarker functions by enabling the "track biomarker" check box.
8. You can change the edge distances with the "edge size" control.
9. You can choose the graph method display.
10. Search a specific molecule, first enabling the "jumping" check box, and then selecting a molecule using the "jump to a molecule" menu: the Demonstration will show you the relevant network, showing the molecule as yellow.
11. Select the fold-change threshold using the "threshold" control bar.
12. You can display molecule information as a tooltip by mousing over a disk.
References
[1] E. Wurmbach, Y. B. Chen, G. Khitrov, W. Zhang, S. Roayaie, M. Schwartz, I. Fiel, S. Thung, V. Mazzaferro, J. Bruix, E. Bottinger, S. Friedman, S. Waxman, and J. M. Llovet, "Genome-Wide Molecular Profiles of HCV-Induced Dysplasia and Hepatocellular Carcinoma," Hepatology, 45(4), 2007 pp. 938–947, PubMed PMID: 17393520. http://onlinelibrary.wiley.com/doi/10.1002/hep.v45:4/issuetoc.
[4] T. Kondo, "Cancer Proteome-Expression Database: Genome Medicine Database of Japan Proteomics," Expert Review of Proteomics, 7(1), 2010 pp. 21–27. http://www.expert-reviews.com/doi/abs/10.1586/epr.09.87?journalCode=epr.
    • Share:

Embed Interactive Demonstration New!

Just copy and paste this snippet of JavaScript code into your website or blog to put the live Demonstration on your site. More details »

Files require Wolfram CDF Player or Mathematica.









 
RELATED RESOURCES
Mathematica »
The #1 tool for creating Demonstrations
and anything technical.
Wolfram|Alpha »
Explore anything with the first
computational knowledge engine.
MathWorld »
The web's most extensive
mathematics resource.
Course Assistant Apps »
An app for every course—
right in the palm of your hand.
Wolfram Blog »
Read our views on math,
science, and technology.
Computable Document Format »
The format that makes Demonstrations
(and any information) easy to share and
interact with.
STEM Initiative »
Programs & resources for
educators, schools & students.
Computerbasedmath.org »
Join the initiative for modernizing
math education.
Step-by-step Solutions »
Walk through homework problems one step at a time, with hints to help along the way.
Wolfram Problem Generator »
Unlimited random practice problems and answers with built-in Step-by-step solutions. Practice online or make a printable study sheet.
Wolfram Language »
Knowledge-based programming for everyone.
Powered by Wolfram Mathematica © 2014 Wolfram Demonstrations Project & Contributors  |  Terms of Use  |  Privacy Policy  |  RSS Give us your feedback
Note: To run this Demonstration you need Mathematica 7+ or the free Mathematica Player 7EX
Download or upgrade to Mathematica Player 7EX
I already have Mathematica Player or Mathematica 7+