RefG Heart Development co-curation (Archived)
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
Number of proposed targets
60 in full list (36 human transcription factor targets)
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. However the current project (May-September 2011) will focus on just the transcription factors that are involved in heart development to take advantage of the recent work on the transcription ontology.
Description of original 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.
From this original target list, 36 human proteins believed to act as transcription factors have been selected.
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
This wiki page will act as a central resource for the project and will be used to help monitoring annotation progress. The attached discussion page will be used to highlight interesting points/difficulties, and 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
- PMID: 19647421 Protein interactions at the heart of cardiac chamber formation
Review of the heart across species.
- PMID: 19592411 'And the beat goes on.' The cardiac conduction system: the wiring system of the heart.
Review of cardiac conduction system development
- PMID: 19390062 Signaling pathways controlling second heart field development
Review of signaling in second heart field development
- PMID: 19371733 Shaping the zebrafish heart: from left-right axis specification to epithelial tissue morphogenesis
Review of zebrafish heart development
- PMID: 17098821 Another key role for the cardiac neural crest in heart development
Neural crest cell contribution to heart development
- PMID: 20186050 The molecular genetics of congenital heart disease: a review of recent developments
Review of transcription factors involved in heart development
- PMID: 20201901 Developmental basis of adult cardiovascular diseases
EMT contribution to heart valve development
Heart Development Transcription Annotation Targets
|Annotation period (week beginning)||Panther Families||Gene Symbol of representative family members (Human protein ID)||PAINT due to begin||GOA / BHF-UCL||MGI||RGD||ZFIN||Wormbase||Flybase||Agbase||Dictybase||TAIR||SGD||Pombase|
|Week 1 (9th May 2011)||PTHR10071||GATA4 (P43694)||done||done||done||elt-1 - done||done|
|Week 2-3 (16th May 2011)||PTHR10032, PTHR24338||OVOL2 (Q9BRP0), MSX1 (P28360)||done||done||done|
|Week 4 (31st May)||PTHR10270||SOX17 (Q9H6I2)||done||done|
|Week 5 (7th June)||PTHR10985, PTHR22793||HEY2 (Q9UBP5), MYCD (Q8IZQ8)|
|Week 6-7 (14th June)||PTHR11267, PTHR23349||TBX3 (O15119), HAND2 (P61296)|
|Week 8 (28th June)||PTHR11309, PTHR10812||SMO (Q99835), TFAP2A (P05549)|
|Week 9 (5th July)||PTHR11389||SNAI2 (O43623)|
|Week 10-11 (12th July)||PTHR11945||MEF2C (Q06413)|
|Week 12-13 (26th July)||PTHR11829, PTHR24340||FOXA2 (Q9Y261), NKX2-5 (P52952)|
|Week 14 (9th August)||PTHR12198, PTHR24126||PROX1 (Q92786), ANKR1 (Q15327)|
|Week 15 (9th August)||PTHR12881, PTHR12958||MED1 (Q15648), FOG1 (Q8IX07)|
|Week 16 (16th August)||PTHR13844, PTHR23341||SMARCD3 (Q6STE5), HMGA2 (P52926)|
|Week 17 (23rd August)||PTHR13864, PTHR17045||TAL1 (P17542), CITED2(Q99967)|
|Week 18 (30th August)||PTHR23043||HIF1A (Q16665)|
|Week 19 (6th September)||PTHR24204||ISL1 (P61371)|
|Week 20 (13th September 2011)||PTHR24329||PITX2 (Q99697)|
1. Comprehensively annotate all the priority genes for your species in the PANTHER families listed for that week. Not all MODs will have priority genes in every family. Some MODs will have more than one priority gene in a single family. Write 'done' in relevant row of the table above, once all the priority genes have been annotated.
2. Annotate as many other members of the weekly PANTHER family as possible. Do not worry if all non-priority members of PANTHER family could not be completed within the time frame.
3. Try to move onto the next week's targets at about the dates listed above, to enable simultaneous discussion of genes/ontology developments across MODs.
Original Annotation Targets
|Panther Family||Gene Symbol (Human protein ID)||Human protein ID||Heart Development stage||General process||Support for Role in heart development|
|1||PTHR10568:SF4||DKK1 (O94907)||O94907||Specification of cardiac precursor cells||Wnt/beta-catenin pathway||PMID: 18297060|
|2||PTHR20937:SF2||MESP2 (Q0VG99)||Q9BRJ9 Q0VG99||Specification of cardiac precursor cells||Wnt/beta-catenin pathway||PMID: 11369261 | MP:0008825 | PMID: 10887078|
|3||PTHR24204:SF26||ISL1 (P61371)||P61371||Specification of cardiac precursor cells||PMID: 19571884 PMID: 17519333|
|4||PTHR11267:SF15||T (O15178); brachyury||O15178||Specification of cardiac precursor cells||Transcription factor||PMID: 18767184|
|5||PTHR22793:SF4||MYOCD (Q8IZQ8)||Q8IZQ8||Specification of cardiac muscle cells||regulation of smooth muscle gene expression||PMID: 15907818 Heart experts|
|6||PTHR11945:SF24 PTHR11945:SF46||MEF2A (Q02078)||Q02078||Cardiac muscle cell specification||Transcription factor||PMID: 10458488 | PMID: 11316766 | PMID: 16469744|
|7||PTHR18973:SF26||ISL1 (P61371)||P61371||Expressed by cardiac progenitor cells||Beta-catenin signaling Hedgehog-smoothened signaling||PMID: 17519333|
|8||PTHR23349:SF3||HAND1 (O96004); eHAND||O96004||Ventricular morphogenesis||Transcription factor||PMID: 19586923 | PMID: 18276607|
|9||PTHR12198:SF0||PROX1 (Q92786)||Q92786||Cardiomyocyte morphogenesis||Transcription factor||PMID:19091769|
|10||PTHR11945:SF25||MEF2C (Q06413)||Q06413||Myocardium development||Transcription factor||PMID: 19899118|
|11||PTHR22824:SF3||AKAP13 (Q12802)||Q12802||Myocardium development||Kinase signaling||PMID: 20139090|
|12||PTHR11878:SF6||SLC8A1 (P32418)||P32418||Sodium ion transport||MP:0003974|
|13||PTHR13703:SF20||SMAD6 (O43541)||O43541||TGF-beta signaling||MP:0003974|
|14||PTHR10032:SF32||OVOL2 (Q9BRP0)||Q9BRP0||Seems to have a role in development in general, but is on BHF list||Notch signaling||MP:0003974|
|15||PTHR23341:SF2||HMGA2 (P52926)||P52926||Cardiomyocyte differentiation||Regulation of NKX2.5 transcription||PMID: 18425117|
|16||PTHR12027:SF7||WNT11 (O96014)||O96014||Cardiovascular progenitor cells||Beta-catenin signaling||PMID: 17519333|
|17||PTHR23349:SF19||HAND2 (P61296); dHAND||P61296||Cardiac muscle cell differentiation||Transcription factor||PMID: 20144608 | PMID: 19607825|
|18||PTHR11036:SF11||SEMA6D (Q8NFY4)||Q8NFY4||Cardiac cell migration||semaphorin-plexin signaling pathway||PMID: 14977921|
|19||PTHR22625:SF13||PLXNA1 (Q9UIW2)||Q9UIW2||Cardiac cell migration||semaphorin-plexin signaling pathway||PMID: 14977921|
|21||No panther family?||C2CD3 (Q4AC94)||Q4AC94||MP:0004252|
|23||PTHR10494:SF2||NOG (Q13253); Noggin||Q13253||BMP inhibition||MP:0004252|
|35||PTHR14066:SF3||NPPA (P01160); ANF||P01160||Heart chamber marker||natriuretic peptide family||PMID: 2522772 | PMID: 2147704|
|36||PTHR10812:SF8||TFAP2 (P05549)||P05549||Heart morphogenesis||Transcription factor||PMID: 18275040 | PMID: 14975722|
|37||PTHR11267:SF26||TBX20 (Q9UMR3)||Q9UMR3||Heart morphogenesis||Transcription factor||PMID: 18834961 | PMID: 17668378 | Heart experts|
|38||PTHR11389:SF375||SNAI1 (O95863)||O95863||Cardiac cushion morphogenesis||Epithelial-to-mesenchymal transition (EMT)||PMID: 18663143|
|39||PTHR23349:SF6||TWIST1 (Q15672)||Q15672||Cardiac neural crest morphogenesis||Epithelial-to-mesenchymal transition (EMT)||PMID: 18539270|
|40||PTHR11848:SF58||NODAL (Q96S42)||Q96S42||Left/right patterning||BMP signaling||PMID: 19064609|
|41||PTHR17045:SF2||CITED2 (Q99967)||Q99967||Left/right patterning||Heart morphogenesis, specifically cardiac septal defects||PMID: 15750185 | MP:0004252|
|42||PTHR24329:SF179||PITX2 (Q99697)||Q99697||Left/right patterning||Wnt/beta-catenin pathway||PMID: 12464179|
|43||PTHR11309:SF35||SMO (Q99835)||Q99835||Left/right patterning||Hedgehog-smoothened signaling||PMID: 16687132 | PMID: 11517919|
|44||PTHR11889:SF17||IHH (Q14623)||Q14623||Left/right patterning||Hedgehog-smoothened signaling||PMID: 11517919|
|45||PTHR11201:SF220||DLL1 (O00548)||O00548||Left/right patterning||Regulation of transcription, Notch signaling||MP:0004252|
|46||PTHR11829:SF1||FOXA2 (Q9Y261); HNF-3 beta||Q9Y261||Possible roles in left/right patterning and heart looping||Regulation of transcription||PMID: 12062060 | MP:0004252|
|47||PTHR12958||ZFPM1 (Q8IX07); FOG1||Q8IX07||Heart looping||Transcription factor?||PMID: 14614148|
|48||PTHR11945:SF32||SRF (P11831); serum response factor||P11831||Heart looping||Transcription factor||PMID: 15492011 | Heart experts|
|49||PTHR10799:SF70||CHD7 (Q9P2D1)||Q9P2D1||Seems to have a role in development in general, but is on BHF list.||DNA helicase?||PMID: 17661815 | Heart experts|
|50||PTHR12881:SF2||MED1 (Q15648)||Q15648||Seems to have a role in development in general, but is on BHF list||Brings transcription factor (GATA1) and RNA pol II together||PMID: 17132730|
|51||PTHR10373:SF11||LEF1 (Q9UJU2)||Q9UJU2||Cannot find evidence of heart development role. But is on BHF list and came up in PMID:18593560 microarray analysis||Wnt signalling, transcription factor||PMID: 18579517|
|52||PTHR24338:SF137||MSX2 (P35548)||P35548||Atrioventricular myocardium and AV valve formation||BMP signaling, Notch signaling||PMID: 18667074|
|53||PTHR10985:SF9||HEY2 (Q9UBP5); HESR2||Q9UBP5||Ventricular septation, blood vessel development||Notch signaling||PMID: 16165016|
|54||PTHR24247:SF85||HTR2B (P41595)||P41595||Possible role in heart valve development||ErbB-2 receptor signaling||PMID: 11728882 | PMID: 18511249|
|55||PTHR24838:SF73||NOTCH1 (P46531)||P46531||Left ventricle development||Epithelial-to-mesenchymal transition (EMT)||PMID: 18593716|
|56||PTHR12365||SPRY1 (O43609)||O43609||Outflow tract development||ERK cascade||PMID: 15306693|
|57||PTHR23043:SF7||HIF1A (Q16665)||Q16665||Angiogenesis||Epithelial-to-mesenchymal transition (EMT)||PMID: 19491109 | MP:0004252|
|58||PTHR13844||SMARCD3 (Q6STE5); Baf60c||Q6STE5||Left/right patterning||Notch signaling||PMID: 17210915 | PMID: 15525990 | Heart experts|
|59||PTHR18958:SF179||ANKRD1 (Q15327)||Q15327||myofibrillar stretch-sensor system||Regulation of transcription||PMID: 19299913 | PMID: 18956313|
|60||PTHR11267:SF20||TBX18 (O95935)||O95935||Cardiac conduction system development||Transcription factor||PMID: 19213963|