drug repurposing by hetnet relationship prediction:

A NEW HOPE

Daniel Himmelstein

iPQB Journal Club

Leap Day 2016

The hetnet is a pathway to many abilities some consider to be unnatural

Slides online at http://slides.com/dhimmel/a-new-hope
// Find CbGiGpBP where first gene is expressed in the CNS
MATCH (n0:Compound)
OPTIONAL MATCH paths = 
  (n0)-[:BINDS_CbG]-(n1)-[:INTERACTS_GiG]-(n2)-[:PARTICIPATES_GpBP]-(n3:BiologicalProcess)
WHERE n3.identifier = 'GO:0042552' // myelination
AND exists((:Anatomy {identifier: 'UBERON:0001017'})-[:EXPRESSES_AeG]-(n1))
WITH
  n0 AS source, paths,
  // Extract the degrees along each path
  [
    size((n0)-[:BINDS_CbG]-()),
    size(()-[:BINDS_CbG]-(n1)),
    size((n1)-[:INTERACTS_GiG]-()),
    size(()-[:INTERACTS_GiG]-(n2)),
    size((n2)-[:PARTICIPATES_GpBP]-()),
    size(()-[:PARTICIPATES_GpBP]-(n3))
  ] AS degrees
RETURN
  source.identifier AS drugbank_id,
  source.name AS drugbank_name,
  count(paths) AS path_count,
  sum(reduce(pdp = 1.0, d in degrees| pdp * d ^ -0.5)) AS DWPC
ORDER BY DWPC DESC, drugbank_name

Candidate compounds for remyelination

// Find CbGiGpBP paths between Marimastat and myelination
MATCH paths = 
  (n0:Compound)-[:BINDS_CbG]-(n1)-[:INTERACTS_GiG]-(n2)
               -[:PARTICIPATES_GpBP]-(n3:BiologicalProcess)
WHERE n0.identifier = 'DB00786' // Marimastat
  AND n3.identifier = 'GO:0042552' // myelination
  // Expressed in the central nervous system
  AND exists((:Anatomy {identifier: 'UBERON:0001017'})-[:EXPRESSES_AeG]-(n1))
RETURN paths

Paths for marimastat–myelination

Drug repurposing by hetnet relationship prediction: a new hope

By Daniel Himmelstein

Drug repurposing by hetnet relationship prediction: a new hope

The Rebels have searched the galaxy and obtained neo4j technology. They now plan to use the force on hetnets to predict new uses for existing drugs. Learn to use the dark side of the force and stop the Rebels before they destroy the Empire. (My presentation for iPQB Journal Club on February 29, 2016.)

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