Network name: D:\drugdatasetinput.txt
Network type: Directed
Number of nodes: 121320
Number of edges: 434800
Number of single edges: 307859
Number of mutual edges: 126941

Algorithm: enumeration
Subgraph size: 3

Generated 1000 random networks
with locally constant number of bidirectional edges,
3 exchanges per edge and 3 tries per edge.

172022813 subgraphs were enumerated in the original network.
197199994016 subgraphs were enumerated in the random networks.
197372016829 subgraphs were enumerated in all networks.

For the random networks: 1578398185 tries were made, 1274251639 were successful.
Randomization took 30053.2 seconds.
Enumeration took 697127 seconds.

Output Files:

• Output
• HTML Overview

Size 3 Subgraph (100,000 Samples, 100 Random Network)

• Approximate number of subgraphs: 265326840 (based on 100000 samples)
• 172022813 subgraphs were enumerated in the original network.
• Result File

Size 6 Subgraph (100,000 Samples, 100 Random Network)

• Approximate number of subgraphs: 9365924517517080 (based on 100000 samples)

MFINDER1.2

3 (Default Settings)

• -

6 (Default Settings)

• -

• There are 86 Edges and 76 Nodes in total in the neighbourhood for this motif. (162)
• The similarity between the compound Chlorpromazine and Trimeprazine has a 0.85 Tanimoto co-efficient.
• There are 60 other compounds that bind to the H1 Histamine Receptor.
• Chlorpomazine has 3 other similar drugs. (Tanimoto is 0.85 for all)
• Trimeprazine is similar to 4 additional compounds. Tanimoto betweeen 0.87 – 1.0.
• The H1 Histamine Receptor has 1 additional target and is associated with 2 proteins one of which has a similar structure.

Motif A (Lenalidomide)

• Total of 21 Nodes and 25 Edges in this motif. (46)
• Lenalidomide has 1 additional target.
• Talidomide has 2 additional targets.
• 0.85 is the tanimoto coefficient in both directions if Lenalidomide and Talidomide.
• TNF has 14 other drugs that bind to it and 1 Protein.

Motif C (Isradipine)

• Blast score between CACH2 and SCN4A is 2.0E-63.
• Blast score in the reverse direction is 1.0E-59.

• Removed all motifs where both similar drugs bind to the target.
• 30,231 motifs were originally identified, now 27,499 (-2,732).

TypeB

• Removed motifs where the drug binds to both targets.
• 22,864 motifs were orignally identified, now 19,185 (-3,679).

TypeC

• Removed motifs where protein(1) inv_in disease(2) or protein(2) inv_in disease(1).
• 70,866 motifs were orignally identified in the dataset, now 70,715 (-151).
• Tried: Remove motifs where the target connects to protein(2), this did not take into account that some links are has_similar_sequence/structure and not is_a. 200 (-70,515).
• Removed motifs with target is_a protein2, made no difference to total.

Ondex

• Selecting a node with a certain id in Ondex?
• Too hard when there is 500k nodes
• Search doesn’t work
• Ondex Console: how to use this??? -> help is unavailable surprisingly.

Exported the datasets ready for using with software (motif finder) that searches for motifs that are overrepresented. (Hypergeometric tests: 1day work). Cytoscape has a plugin.

• ib_2010_data.1.xml.gz –> .dot (50mb)
• ib_2010_data.1.xml.gz –> graph htm??? (cant remeber but it was 450mb)

Motif Type C

Trying to define another motif, struggling… similar targets?

B

Plan

Results/Code/Other program (June-July 2010)

4 Weeks

• Week 1 – Code/Motif Finder (i.e. Motif A,B,C… x,y,z instances)
• Week 2 – Java/Score/FoundExamples
• Week 3 – Score
• Week 4 – Score

Paper (July-August 2010)

• Intro
• Background
• Methods

- Definitions of S.M.
- Searching
- Scoring

• Results
  • TypeA
  • TypeB
  • TypeC
• Discussion
  • Future work
• Abstract

Module Webpage

Example output from Java (cutoff dataset):

Code was ran on the updated dataset:

• There were 70,866 instances of this motif definition in the dataset.
• However, this doesn’t address the issue of the OMIM database. So many of these will not have true “Diseases”. This would probably be best addressed when trying to score this type, if its even possible to do this.

• The issue with ‘Comp:Compound‘ is being resolved compounds will be known as ‘Compound‘ after the fix.
• Disease nodes – Some are diseases and some are not diseases, they are other things such as Genes due to OMIM.
• Find more examples like Chlorprazine and more complex ones.

Update: Dataset has been updated

• 30,231 Motifs (Basic Type) is now the latest count.
• Still can’t get to print Concept names out (Doing it wrong?)

New dataset info:

• Drug 1 – Chlorpromazine – ID:120943
• Drug 2 – Trimeprazine – ID:120836
• Target – Histamine H1 Receptor – ID:715

I then traversed the output of the java code in Ondex Mini, and sucessfully found the motif:

Definition of a more complex example

• Started an implementation of a more complex motif i.e. look for similar proteins.
• Developed it using the chart created on a previous post.
• Seems to be working okay, although there are some issues with the Disease output and when to increment the motif counter/add to the motif Set.