Schistosoma mansoni genome prioritization

Posted by Santiago Carmona on 2009-07-09 16:54:40

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For this genome prioritization we considered several filters independently and
calculated the weighted (ranked) UNION of these, so we don`t exclude targets
that miss some of the criteria. We considered lethal and some non-lethal mutant
phenotypes in C. elegans and D. melanogaster or in ANY species (although
non-lethals have a lower weight); expression data from ESTs obtained from
SchistoDB (expressed in ANY relevant stage, but also giving a higher weight if
expressed in more than one relevant stage); druggability inferred by sequence
similarity against known druggable targets; availability of structural models
in Modbase; and gave a negative weight to the presence of orthologous genes in
human.

D. melanogaster knock-out phenotypes were downloaded from FlyBase, and mapped
to Schistosoma mansoni genes through OrthoMCL clusters. EST data was obtained
from SchistoDB.

I have also included the top targets list from Caffrey et al.: the top 35
targets (with orthologs in D.melanogaster AND C.elegans, with deleterious
mutant phenotypes in these model organisms, expressed in relevant stages, and
orthologs to known druggable genes described in literature), and top 18 targets
(which are also homologous to proteins with 3d structures including
co-crystallized ligands).

These two lists have not been given a weight so: i) they don't affect our prioritization but ii) they appear in the final list so we can see where they rank in our list.

● A comparative chemogenomics strategy to predict potential drug targets in the metazoan pathogen, Schistosoma mansoni. (2009). PLoS ONE 4: e4413 PubMed, Publisher.

Queries in this set

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  Orthologs of D. melanogaster genes with mutant phenotype lethal (2207 records). Show parameters.

  Orthologs of D. melanogaster genes with mutant phenotype neurophysiological defect (382 records). Show parameters.

  Embryonic Lethal/Arrest in C. elegans (2269 records). Show parameters.

  Growth Defect in C. elegans (1195 records). Show parameters.

  Larval/Adult Lethal/Arrest in C. elegans (1476 records). Show parameters.

  Morphology Defect in C. elegans (787 records). Show parameters.

  Sterility in C. elegans (1550 records). Show parameters.

  any essentiality evidence (3209 records). Show parameters.

  in human (7394 records). Show parameters.

  structural model available (8831 records). Show parameters.

  druggable genes inferred by sequence simiarity (846 records). Show parameters.

  expressed in adult worm (ESTs) (6961 records). Show parameters.

  expressed in egg stage (ESTs) (4955 records). Show parameters.

  expressed in schistosomula stage (ESTs) (5249 records). Show parameters.

  expressed in any relevant stage (ESTs) (8618 records). Show parameters.

  Caffrey et al TOP 18 (18 records). Show parameters.

  Caffrey et al TOP 35 (35 records). Show parameters.

  Union of (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17) (11179 records). Show parameters.