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1 Centre  for  Cardiovascular  GeneLcs,  InsLtute  of  Cardiovascular  Science,  Rayne  Building,  5  University  Street,  University  College  London,  WC1E  6JF.
2 King’s  BriLsh  Heat  FoundaLon  Centre,  King’s  College  London,  London  SE5  9NU.
3 Gene  Ontology  AnnotaLon  (GOA)  Project,  European  BioinformaLcs  InsLtute,  Hinxton,  Cambridge,  CB10  1SD.
4 European  Molecular  Biology  Laboratory,  European  BioinformaLcs  InsLtute  (EMBL-­‐EBI),  Wellcome  Trust  Genome  Campus,  Hinxton,  Cambridge  CB10  1SD.
The  Cardiovascular  Gene  AnnotaLon  IniLaLve  at  UCL  represents  a  collaboraLon   between  UCL,  King’s  College  London  and  EMBL-­‐EBI,  funded  by  the  BriLsh  Heart
FoundaLon.   We   aim   to   capture   protein   interacLons   and   curate   experimental   data  by  creaLng   G ene   O ntology  ( G O )  annotaLons,  by  manual  literature  curaLon.
News !
Following   a   successful   grant   applicaLon   to   Parkinson’s   UK
(
),  a  new  collaboraLon  is  established  between
John   Hardy   (UCL   InsLtute   of   Neurology),   the   UCL   gene   annotaLon   group  and  EMBL-­‐EBI,  extending  annotaLons  to  the  neurological  field.
th
Register  online  at
This   2-­‐day   course   is   open   to   all   biological   or   biomedical   scienLsts   including  PhD  students,  Post-­‐doctoral  and  established  researchers.
Based  on  the  EBI  staLsLcs
,  on  12th  October  2013,  our  project  has  associated  29,547  GO  terms  to  4,000  proteins,  20,370  of  which  are  to  2,300  human  proteins.  During  the  process  of  GO   annotaLon  we  have  curated  1100  papers  that  described  protein-­‐protein  interacLons  (PPIs).  As  these  PPIs  are  not  automaLcally  exported  to  PPI  databases,  our  current  annotaLon  focus  is  to  re-­‐annotate  the  interacLons  to  the
EMBL-­‐EBI  database  IntAct
.    For  example:  to  date  43  papers  have  been  re-­‐annotated  leading  to  the  creaLon  of  285  PPIs.  Specifically,  for  WNT  signalling:  114  PPIs  have  been  captured  from  14  papers,  with  35   more  papers  pending.
!
:  to  enrich  the  PPIs  of  telomere/telomerase  associated  proteins  in  the  IntAct  database  starLng  by  re-­‐annotaLng  the  binary  interacLons  which  we
had  submieed  to   G O   into  IntAct.
:  a  group  of  six  telomere/telomerase  associated  proteins  were  extracted  from  our  list  of  PPIs  in  GO.  The  relevant  papers  were  idenLfied  and   manually  curated  into  IntAct  according  to  the  required  standards.
:  the  binary  interacLons  more  than  doubled  (from  13  to  29)  and  the  number  of  associated  proteins  increased  from  17  to  31  (see  figure  1).
Also,  a  newly  annotated  binary  interacLon  resulted  in  linking  two  clusters  which  were  not  connected  before.
:  the  impact  of  the  new  annotaLon  focus  is  already  evident  in  the  PPI  network  despite  the  relaLvely  short  period  of  Lme  of  two  months.
However,  these  networks  are  not  truly  representaLve,   yet .  For  example,  a  simple  query  of  IntAct  for  POT1,  one  of  the  proteins  known  to  be  involved   in  the  shelterin  complex,  reveals  this  protein  has  been  well  annotated.  However,  the  shelterin  PPI  network  cluster  is  not  currently  linked  to  our  set   of  interacLons,  which  we  would  expect  it  to  be.  Our  method  of  enriching  our  networks  through  focused  annotaLons  is  promising.  However,  further
work  is  needed  to  develop  the  PPIs  annotaLons  further  so  as  to  reflect  the  scienLfic  literature  and  knowledge  more  appropriately.
:  to  conLnue  with  the  focused  annotaLon  effort.     a) b)
1.
Gene  Ontology  ConsorLum.  CreaLng  the  gene  ontology  resource:  design  and  implementaLon.   Genome  Res.
11,  1425–1433  (2001).
2.
Nandakumar,  J.  &  Cech,  T.  R.  Finding  the  end:  recruitment  of  telomerase  to  telomeres.   Nat.  Rev.  Mol.  Cell  Biol.
14,  69–82  (2013).
3.
Gene  Ontology  ConsorLum.  The  Gene  Ontology:  enhancements  for  2011.   Nucleic  Acids  Res.
40,  D559–564  (2012).
4.
Kerrien,  S.   et  al.
The  IntAct  molecular  interacLon  database  in  2012.   Nucleic  Acids  Res.
40,  D841–846  (2012).
The  work  of  the  BHF-­‐  UCL  annotaLon   group  is  supported     by   Bri)sh  Heart  Founda)on  grant  RG/
13/5/30112
Figure  1:  IntAct  PPI  network  views  of  PPIs  associated  with  TERT,  NAFT1  and  OBFC1.  a)  Before  annotaLon   effort  (accessed  on  5  Sept  2013).  b)  Aier    annotaLon  effort  (accessed  on  29  Oct  2013).