Dr Helen Lockstone
Head of Functional Data Analysis
Wellcome Trust Centre for Human Genetics, Roosevelt Dr.
I joined the Bioinformatics and Statistical Genetics Core in 2006 as a microarray data analyst and am now in charge of all the functional data analysis that we perform. Using both sequencing and microarray technologies, the Oxford Genomics Centre generates a variety of functional genomics datasets for customers within the WTCHG, Oxford and beyond. These include studies to investigate gene expression and alternative splicing, methylation, transcription factor binding sites, microRNAs and DNAse I hypersensitivity sites. The data reveal information about the transcriptome and its regulation on a genome-wide scale, providing important insights to a wide variety of systems and helping to understand the molecular basis of disease.
Our role is to support researchers performing this type of experiment in their research. This involves advising on experimental design, identifying and implementing the best analysis tools for each data type, performing analysis, helping with biological interpretation and communicating results. In addition, we work closely with High-Throughput Genomics to evaluate the quality of data being generated and to test new lab protocols.
We have recently undertaken a detailed comparison of gene expression profiling using microarrays and sequencing approaches and found that, despite some differences, both technologies capture a similar picture of the underlying biology overall. This helps confirm the validity of both approaches and their continued widespread use as hypothesis-generating tools. For a quick assessment of gene expression levels, microarrays offer a convenient and cheap solution, while RNA-Seq gives the ability to characterise the transcriptome in much greater detail, and is ideal for more in-depth studies. The choice really depends on the experimental question and we encourage anyone thinking of using the Oxford Genomics Centre to come and discuss their plans with us at an early stage.
Prior to joining the WTCHG, I worked at the University of Cambridge for 4 years as a Bioinformatician in Dr Sabine Bahn's lab, where genomic, proteomic and metabolomic techniques were used to investigate schizophrenia and bipolar disorder, and found this a fascinating area of research. I originally studied Physics at King's College London (1999-2002) and obtained an MSc in Bioinformatics from the University of Exeter in 2003.
Waller-Evans H, Hue C, Fearnside J, Rothwell AR, Lockstone HE, Caldérari S, Wilder SP, Cazier JB, Scott J, Gauguier D. Nutrigenomics of High Fat Diet Induced Obesity in Mice Suggests Relationships between Susceptibility to Fatty Liver Disease and the Proteasome. PLoS One. 2013 Dec 6;8(12):e82825. doi: 10.1371/journal.pone.0082825. PubMed PMID: 24324835; PubMed Central PMCID: PMC3855786.
Crawford G, Enders A, Gileadi U, Stankovic S, Zhang Q, Lambe T, Crockford TL, Lockstone HE, Freeman A, Arkwright PD, Smart JM, Ma CS, Tangye SG, Goodnow CC, Cerundolo V, Godfrey DI, Su HC, Randall KL, Cornall RJ. DOCK8 is critical for the survival and function of NKT cells. Blood. 2013 Sep 19;122(12):2052-61. doi: 10.1182/blood-2013-02-482331. Epub 2013 Aug 8. PubMed PMID: 23929855; PubMed Central PMCID: PMC3778549.
Domingo E, Ramamoorthy R, Oukrif D, Rosmarin D, Presz M, Wang H, Pulker H, Lockstone H, Hveem T, Cranston T, Danielsen H, Novelli M, Davidson B, Xu ZZ, Molloy P, Johnstone E, Holmes C, Midgley R, Kerr D, Sieber O, Tomlinson I. Use of multivariate analysis to suggest a new molecular classification of colorectal cancer. J Pathol. 2013 Feb;229(3):441-8. doi: 10.1002/path.4139. PubMed PMID: 23165447; PubMed Central PMCID: PMC3588155.
Adam J, Hatipoglu E, O'Flaherty L, Ternette N, Sahgal N, Lockstone H, Baban D, Nye E, Stamp GW, Wolhuter K, Stevens M, Fischer R, Carmeliet P, Maxwell PH, Pugh CW, Frizzell N, Soga T, Kessler BM, El-Bahrawy M, Ratcliffe PJ, Pollard PJ. Renal cyst formation in Fh1-deficient mice is independent of the Hif/Phd pathway: roles for fumarate in KEAP1 succination and Nrf2 signaling. Cancer Cell. 2011 Oct
18;20(4):524-37. doi: 10.1016/j.ccr.2011.09.006. PubMed PMID: 22014577; PubMed Central PMCID: PMC3202623.
Vernes SC, Oliver PL, Spiteri E, Lockstone HE, Puliyadi R, Taylor JM, Ho J, Mombereau C, Brewer A, Lowy E, Nicod J, Groszer M, Baban D, Sahgal N, Cazier JB, Ragoussis J, Davies KE, Geschwind DH, Fisher SE. Foxp2 regulates gene networks implicated in neurite outgrowth in the developing brain. PLoS Genet. 2011 Jul;7(7):e1002145. doi: 10.1371/journal.pgen.1002145. Epub 2011 Jul 7. PubMed
PMID: 21765815; PubMed Central PMCID: PMC3131290.
Vandiedonck C, Taylor MS, Lockstone HE, Plant K, Taylor JM, Durrant C, Broxholme J, Fairfax BP, Knight JC. Pervasive haplotypic variation in the spliceo-transcriptome of the human major histocompatibility complex. Genome Res. 2011 Jul;21(7):1042-54. doi: 10.1101/gr.116681.110. Epub 2011 May 31. PubMed PMID: 21628452; PubMed Central PMCID: PMC3129247.
Lockstone HE. Exon array data analysis using Affymetrix power tools and R statistical software. Brief Bioinform. 2011 Nov;12(6):634-44. doi: 10.1093/bib/bbq086. Epub 2011 Apr 15. PubMed PMID: 21498550; PubMed Central PMCID: PMC3220870.
Krausgruber T, Blazek K, Smallie T, Alzabin S, Lockstone H, Sahgal N, Hussell T, Feldmann M, Udalova IA. IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nat Immunol. 2011 Mar;12(3):231-8. doi: 10.1038/ni.1990. Epub 2011 Jan 16. PubMed PMID: 21240265.