RefG Heart Development co-curation (Archived)

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Title of Project: Heart Development co-curation

Lead group, lead curator

BHF-UCL group, Varsha Khodiyar; Cardiovascular GO annotation initiative

Reference Genome Start Date Preference

April 2010

Number of proposed targets

60

Short description to background of proposed project

The recent ontology workshop on heart development terms means that the ontology to support the annotation of this set of genes already exists.


The heart is interesting from an evolutionary standpoint, for example fish have a 4-chambered heart, with the chambers arranged in a sequential manner, and frogs have a 3-chambered heart. Therefore it will be interesting to see how the functions of the gene products change across species.


The heart is also of interest from the viewpoint of human health. There are many model organisms used to study the heart and this project will help to annotate the gene products of organisms that are important to cardiovascular research, but are not reference genome species, for example the dog.


The target list is rich in proteins involved in a number of central signaling pathways, TGF-beta and Wnt-catenin signaling for example. Thus, the annotation of this set will also serve as a through test and aid ongoing improvements of the new signaling ontology.

Description of target selection

During the heart development workshop, the heart experts were asked for their opinions as to which genes were important in specific developmental processes. This list was combined with literature reviews to generate further genes of interest. This set was sent back to the heart experts for review and 4 of their additional suggestions were incorporated. Additionally, 18 targets have been included for which the only evidence gathered is that the mouse ortholog has been annotated with one (or more) of the following mammalian phenotype terms:

  • MP:0003974 - abnormal endocardium morphology
  • MP:0008825 - abnormal cardiac epithelial to mesenchymal transition
  • MP:0004252 - abnormal direction of looping morphogenesis

It expected that as annotation proceeds, the literature will further support the inclusion of these targets in the heart development set.

There are a number of other mammalian phenotype terms which are relevant to heart development, but which have not been selected in this target set. The reason is that the aim was to generate a list of only 60 panther families. However, as the annotation proceeds it is likely that additional targets will become obvious, the annotation of which would help the heart development annotation set to feel more complete. So if possible, it is suggested that the option of adding an extra month to the project would be beneficial. This would allow time for the annotation of new targets that have come out of the initial 3-month project.


Previous reference genome targets

The initial heart development set from the experts included 24 previous reference genome targets. Of these, seven were ref genome targets prior to May 09 and so it is felt that they will benefit from further annotation with the updated ontology. The remaining 17 were in the mouse lung target set. Of these only 3 of the human genes are fully annotated at the time of writing. The remaining 14 require annotation both for the mouse lung project and the heart development project. It is suggested these 14 targets are given the highest possible priority, as they are important for both the mouse lung project and heart development. However, as they had been selected previously they are not included in the set of 60 heart development targets.


Limitations of target set

The Panther subfamily has been specified where possible in order to minimize the number of non-heart development related proteins included in each family. Where there are multiple targets within a panther group, the family member specifically shown to be involved in heart development will be highlighted on the wiki as a higher priority than other non-heart development related family members. Many of the proposed targets may not be represented by orthologues in non-chordate species. Therefore an alternative set of targets may need to be found for Reference Genome groups annotating to non-chordate species.


Reference Genome Annotation Plans

A central document page will be developed and be accessible by all concerned. This page will act as a central resource for the project and will help in monitoring progress, highlight interesting points/difficulties, supported by email communication between all the curators involved. The page should also capture any data that could be considered for publication purposes.


Ideas for annotation data exploitation

The annotations will be analyzed at the end of the project, to see if GO annotations can highlight the functional differences between species. Ongoing contact with heart development experts will be maintained to seek additional value for the project.


Heart Development Review Papers

  1. PMID: 19647421 Protein interactions at the heart of cardiac chamber formation

Review of the heart across species.

  1. PMID: 19592411 'And the beat goes on.' The cardiac conduction system: the wiring system of the heart.

Review of cardiac conduction system development

  1. PMID: 19390062 Signaling pathways controlling second heart field development

Review of signaling in second heart field development

  1. PMID: 19371733 Shaping the zebrafish heart: from left-right axis specification to epithelial tissue morphogenesis

Review of zebrafish heart development

  1. PMID: 17098821 Another key role for the cardiac neural crest in heart development

Neural crest cell contribution to heart development

  1. PMID: 20186050 The molecular genetics of congenital heart disease: a review of recent developments

Review of transcription factors involved in heart development

  1. PMID: 20201901 Developmental basis of adult cardiovascular diseases

EMT contribution to heart valve development