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Systematic prediction of novel gene targets associated to mitosis:. Integration of prediction methods. Experimental validation. Novel s pindle proteins. Fisher. 1).

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Systematic prediction of novel gene targets associated to mitosis:


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Presentation Transcript
slide1

Systematicprediction of novel gene targets associatedto mitosis:

Integration of predictionmethods

Experimental validation

Novel

spindle

proteins

Fisher

1)

Rojas et al. Uncoveringthe molecular machinery of the human spindle--anintegration of wet and drysystemsbiology. PLoSOne. 2012;7(3):e31813

Kernels

Novel

Chromos.

Conden.

Genes

2)

Jean-KarimHériché et al. …& Jan Ellenberg. Integration of biological data by kernels on graph nodes allows prediction of genes involved in mitotic chromosome condensation . Submitted.

slide2

Functionalprediction of novel genes and gene relationshipsrelatedtocellmigration:

3) Case study: ECM stiffnesseffectsin the MCF10CA1a malignanttumourcellline.

Functionalsystemsprediction

usingproteinnetworks and kernels

Diferentiallyexpressed genes

Transcriptomic and proteomic data

In collaborationwithStaffanStrömblad.

slide3

Methodstoidentifygeneticexpressionvariationassociatedwithdrug response in heterogeneoustumours

1)

Tumourlines / taxoltreatment

4)

Tumourlinesseparation:

Sensitive / Resistant

Gene expressionmatrix

+

Celltypesfrequencymatrix

+

Multi-regression

3)

2)

Sensitive / Resistant

Heatmap of theidentified genes

Changes in expressiondependantoncelltypes and drugtreatment response

In collaborationwithAltschuler & Wulab (UT Southwestern). Manuscript in preparation.

slide4

Relationship of genes in differentontologies: Gene Ontology (GO) and experimental phenotypes.

Metricstomeasuregene pairssimilarity in differentontologies:

Metriccorrelationcomparisonstudies:

Semanticsimilarity in GO.

  • Euclideandistance
  • StandarizedEuclideandistance
  • Mahalanobisdistance
  • City Block metric
  • Minkowskimetric
  • Cosinedistance
  • Correlationdistance
  • Hammingdistance
  • HammingModifiedsimilarity
  • Jaccarddistance
  • Clusteringdistance
  • Clusteringsimilarity
  • TF-IDF similarity

Ongoingwork in collaborationwithGabriellaRustici.