UCL Institute of Cardiovascular Science


June 2020

Editor – Ruth Lovering

Many thanks and farewell to Dr Barbara Kramarz

After 4 years as a member of the group, Barbara is now starting a new role as a Lecturer and Programme Coordinator at Oryx Universal College in Doha, Qatar, in partnership with Liverpool John Moores University. In this new role Barbara will build on her higher education teaching experience, gained at UCL, and as a Fellow of the Higher Education Academy. I would like to thank Barbara for all the work she has done at UCL. She was responsible not only for protein and microRNA curation, as part of several different projects, but also contributed to the creation or revision of over 300 GO terms. In addition, her work as Project Coordinator of several ARUK GO annotation projects was key to its success and her teaching skills were much appreciated by the MSc student projects. We wish her all the best and good luck in her lectureship.

Blood-brain barrier annotation progress

The annotation project focused on transport at blood-brain barrier is drawing to a close, with Shirin now curating of this domain. Following the review of over 170 articles and the creation of more than 1,400 GO annotations, only 5 of the 81 human proteins prioritised for annotation by this project still need to be curated. For example SLC29A4, is now associated with GO terms describing the uptake of: serotonin, norepinephrine, histamine, dopamine, epinephrine as well as its role as a neurotransmitter transmembrane transporter in the transport across the blood brain barrier. None of this information was previously associated with SLC29A4, thus, ARUK funding is enabling more comprehensive annotation of Alzheimer’s relevant proteins.

ARUK-UCL Annotation Statistics

In total, all ARUK-UCL projects have resulted in 11,766 annotations for 1,854 distinct gene products, of which 8,554 annotations are associated with 1,131 human gene products (data from QuickGO, 1st June 2020).

Other annotation projects

Following the lockdown in the UK, we are pleased to welcome two more MSc students, Heather Gunn and Renzhi Su. Heather will be using GO to describe the subunits of PI3Kinase, and her project will be co-supervised by Paul Frankel, who brings signalling expertise to the project. Whereas Renzhi will be annotating microRNAs that regulate the PPARG and their potential role in hypertension, his project will be co-supervised by Lucie Clapp, Lucie was key to setting up the UCL-wide pulmonary arterial hypertension consortium.

Despite the lockdown, Ruth has continued to collaborate with GREEKC and has been working closely with Pascale Gaudet and Colin Logie, and many others in the GO Consortium to create a comprehensive list of DNA binding transcription factors and to ensure that the GO Consortium database represents these appropriately. Together this collaboration has led to the checking of over 2000 annotations and revision of over 400, with around 500 annotations still to check.

Meetings attended

Ruth and Pascale organised a ‘remove’ 3-day workshop at the end of April, attended by 14 people (mostly GO curators) to promote the revised ontology, and associated guidelines, for the annotation of DNA binding transcription factors, transcription coregulators and general transcription factors.

In May Ruth and Shirin attended the remote 3-day GO Consortium meeting, due to be held in Paris, where progess to moving GO annotation from simple linear annotations to annotation models was presented, along with progress on increasing the import of Reactome data.

Recent Publications

  • Kramarz B, Huntley RP, Rodríguez-López M, Roncaglia P, Saverimuttu SCC, Parkinson H, Bandopadhyay R, Martin MJ, Orchard S, Hooper NM, Brough D, Lovering RC. Gene Ontology Curation of Neuroinflammation Biology Improves the Interpretation of Alzheimer's Disease Gene Expression Data. J Alzheimers Dis. 2020 May 13. Online ahead of print. PMID: 32417785.
  • Hall CL, Gurha P, Sabater-Molina M, Asimaki A, Futema M, Lovering RC, Suárez MP, Aguilera B, Molina P, Zorio E, Coarfa C, Robertson MJ, Cheedipudi SM, Ng KE, Delaney P, Hernández JP, Pastor F, Gimeno JR, McKenna WJ, Marian AJ, Syrris P. RNA sequencing-based transcriptome profiling of cardiac tissue implicates novel putative disease mechanisms in FLNC-associated arrhythmogenic cardiomyopathy. Int J Cardiol. 2020. 302:124-130. PMID: 31843279.
  • Shah S, Henry A, Roselli C, Lin H, Sveinbjörnsson G, Fatemifar G, Hedman ÅK, Wilk JB, Morley MP, Chaffin MD, Helgadottir A, Verweij N, Dehghan A, Almgren P, Andersson C, Aragam KG, Ärnlöv J, Backman JD, Biggs ML, Bloom HL, Brandimarto J, Brown MR, Buckbinder L, Carey DJ, Chasman DI, Chen X, Chen X, Chung J, Chutkow W, Cook JP, Delgado GE, Denaxas S, Doney AS, Dörr M, Dudley SC, Dunn ME, Engström G, Esko T, Felix SB, Finan C, Ford I, Ghanbari M, Ghasemi S, Giedraitis V, Giulianini F, Gottdiener JS, Gross S, Guðbjartsson DF, Gutmann R, Haggerty CM, van der Harst P, Hyde CL, Ingelsson E, Jukema JW, Kavousi M, Khaw KT, Kleber ME, Køber L, Koekemoer A, Langenberg C, Lind L, Lindgren CM, London B, Lotta LA, Lovering RC, Luan J, Magnusson P, Mahajan A, Margulies KB, März W, Melander O, Mordi IR, Morgan T, Morris AD, Morris AP, Morrison AC, Nagle MW, Nelson CP, Niessner A, Niiranen T, O'Donoghue ML, Owens AT, Palmer CNA, Parry HM, Perola M, Portilla-Fernandez E, Psaty BM; Regeneron Genetics Center, Rice KM, Ridker PM, Romaine SPR, Rotter JI, Salo P, Salomaa V, van Setten J, Shalaby AA, Smelser DT, Smith NL, Stender S, Stott DJ, Svensson P, Tammesoo ML, Taylor KD, Teder-Laving M, Teumer A, Thorgeirsson G, Thorsteinsdottir U, Torp-Pedersen C, Trompet S, Tyl B, Uitterlinden AG, Veluchamy A, Völker U, Voors AA, Wang X, Wareham NJ, Waterworth D, Weeke PE, Weiss R, Wiggins KL, Xing H, Yerges-Armstrong LM, Yu B, Zannad F, Zhao JH, Hemingway H, Samani NJ, McMurray JJV, Yang J, Visscher PM, Newton-Cheh C, Malarstig A, Holm H, Lubitz SA, Sattar N, Holmes MV, Cappola TP, Asselbergs FW, Hingorani AD, Kuchenbaecker K, Ellinor PT, Lang CC, Stefansson K, Smith JG, Vasan RS, Swerdlow DI, Lumbers RT. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure. Nat Commun. 2020. 11(1):163. PMID: 31919418.