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===== A tutorial of hipathia, a mechanistic model of pathway activity  =====
=== The 4th Disease Maps Community Meeting (DMCM2019) is hosted by the Clinical Bioinformatics Area, FPS, Hospital Virgen del Rocío. ===
=== Sevilla - 2-4 October, 2019 ===

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Martha R. Hidalgo 1, Kinza Rian 2, Joaquin Dopazo 2

Centro de Investigación Principe Felipe, Valencia, Spain 1, 
Fundación Progreso y Salud, Sevilla, Spain 2


{{ :dmcm2019:hipathia_-_mozilla_firefox_006.png?direct&400|http://hipathia.babelomics.org/}}

==== Abstract ====
Conventional  gene-based  approaches  ignore  the  modular  nature  of most  human  traits, while pathway enrichment methods produce only illustrative results of limited practical utility. Recently,  new  methods  have  emerged  that  change  the  focus  from  the  whole pathways  to  the  definition  of  elementary circuits  within  them  that have  any  mechanistic  significance.  In  some  cases,  this  involves  the  recodification  of Process  Description  pathways  into  Influence  Maps  that  describe  how  proteins  interact among them  to  trigger  or  carry  out  cell  functionalities.  The  activity  of  such  circuits defined  within  Influence  Map  pathways  is  expected  to  be  a better  descriptor  of  cell functional activity than measurements for whole pathway or single gene activities. 
Here  we  present  a  tutorial  on  the  HiPathia  MPA  method  (1),  implemented  in  a R/Bioconductor package (http://bioconductor.org/packages/devel/bioc/html/hipathia.html)   as   well   as   in   an interactive web application (http://hipathia.babelomics.org/). This tutorial demonstrates  how  to  transform  decontextualized  gene  expression  measurements  into highly-informative  cell  activity  quantitative  values and how to  relate  them  to  phenotypes. Different  analyses  can  be  carried  out  using  circuit  activities  that  include  differential activity  analysis, when  two  conditions  are  compared,  or  relation  of  circuit  activities  to  a continuous  variable.  Since  circuits  modeled  have an associated functional  meaning  (any of  them trigger one or more cell functions, defined by Gene Ontology terms), the results provide direct  clues  to  understand  disease  mechanisms  or  drug  modes  of  action.  It  is  also possible to build predictors directly based on circuit activities, which adds an interesting mechanistic dimension to the prediction process. 
In  addition  to  be  used  to  uncover  the  molecular  basis  of  phenotypes,  mechanistic models can also be used to predict what would be the potential effect of one or several interventions  (KOs,  inhibitions,  over-expressions,  drugs,  etc.)  over  the  system  studied. Thus, the PathAct (2) wen application (http://pathact.babelomics.org/) allows predicting from  a  holistic  perspective  what  would  be  the  effects  of  interventions  over  a  specific system. The  HiPathia  suite  provides  a  friendly  environment  to  use  Influence  Map  pathways as templates of cell functionality to provide a mechanistic interpretation of transcriptomics data.

M. R. Hidalgo et al., High throughput estimation of functional cell activities reveals disease mechanisms and predicts relevant clinical outcomes. Oncotarget 8,5160 (Dec 22, 2017).
F. Salavert et al., Actionable pathways: interactive discovery of therapeutic targets using signaling pathway models. Nucleic Acids Res 44, W212 (Jul 08, 2016)

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=== Venue ===

  * Edificio C.D.C.A.. Hospital Universitario Virgen del Rocío 
  * Avenida Manuel Siurot s/n, 4101,
  * Sevilla, Spain
=== Organizers ===

  * [[http://disease-maps.org/| the Computational Systems Biology of Cancer group, Institut Curie]]
    * [[http://disease-maps.org/DMCM2019|More information on DMCM2019 events]]
  * [[http://www.clinbioinfosspa.es/|Clinical Bioinformatics Area]], Fundación Progreso y Salud, Seville, Spain


==== Instructors ====
=== Clinical Bioinformatics Area team (Hipathia tutorial) ===
  * Kinza Rian
  * Joaquín Dopazo

=== Unidad de Bioinformática y Bioestadística (Hipathia tutorial) ===
  * Martha R. Hidalgo

==== Presentations ====

{{ :dmcm2019:hipathiaTuto.pdf |Hipathia Tutorial}}
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==== Sponsors ====

{{:gatk2018:logo.inb-elixir_es.800px.png?nolink&200|}}{{:gatk2018:logo.feder-ministerio_isciii-prb2.800px.png?500|http://www.prb2.org/home}}

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