Journal articles
Endicott M, Thirlwell C, Webster AP (2023). Exploring genetic loci of type 2 diabetes and cancer: a review. Endocrine Oncology, 3(1).
Maity AK, Stone TC, Ward V, Webster AP, Yang Z, Hogan A, McBain H, Duku M, Ho KMA, Wolfson P, et al (2022). Novel epigenetic network biomarkers for early detection of esophageal cancer.
Clin Epigenetics,
14(1).
Abstract:
Novel epigenetic network biomarkers for early detection of esophageal cancer.
BACKGROUND: Early detection of esophageal cancer is critical to improve survival. Whilst studies have identified biomarkers, their interpretation and validity is often confounded by cell-type heterogeneity. RESULTS: Here we applied systems-epigenomic and cell-type deconvolution algorithms to a discovery set encompassing RNA-Seq and DNA methylation data from esophageal adenocarcinoma (EAC) patients and matched normal-adjacent tissue, in order to identify robust biomarkers, free from the confounding effect posed by cell-type heterogeneity. We identify 12 gene-modules that are epigenetically deregulated in EAC, and are able to validate all 12 modules in 4 independent EAC cohorts. We demonstrate that the epigenetic deregulation is present in the epithelial compartment of EAC-tissue. Using single-cell RNA-Seq data we show that one of these modules, a proto-cadherin module centered around CTNND2, is inactivated in Barrett's Esophagus, a precursor lesion to EAC. By measuring DNA methylation in saliva from EAC cases and controls, we identify a chemokine module centered around CCL20, whose methylation patterns in saliva correlate with EAC status. CONCLUSIONS: Given our observations that a CCL20 chemokine network is overactivated in EAC tissue and saliva from EAC patients, and that in independent studies CCL20 has been found to be overactivated in EAC tissue infected with the bacterium F. nucleatum, a bacterium that normally inhabits the oral cavity, our results highlight the possibility of using DNAm measurements in saliva as a proxy for changes occurring in the esophageal epithelium. Both the CTNND2/CCL20 modules represent novel promising network biomarkers for EAC that merit further investigation.
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Dritsoula A, Kislikova M, Oomatia A, Webster AP, Beck S, Ponticos M, Lindsey B, Norman J, Wheeler DC, Oates T, et al (2021). "Epigenome-wide methylation profile of chronic kidney disease-derived arterial DNA uncovers novel pathways in disease-associated cardiovascular pathology.".
EPIGENETICS,
16(7), 718-728.
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Webster AP, Thirlwell C (2021). The evolving molecular landscape of intestinal and pulmonary neuroendocrine tumours.
Current Opinion in Endocrine and Metabolic Research,
19, 30-34.
Abstract:
The evolving molecular landscape of intestinal and pulmonary neuroendocrine tumours
Neuroendocrine tumours (NETs) are rare clinically and genetically heterogeneous cancers. The biology of well-differentiated neuroendocrine neoplasms is distinct from other solid tumours because of their unusually low mutational burden, and until recently, little progress has been made in understanding the molecular landscape and evolution of these tumours. This impacts accurate diagnosis and prognostication and selection of optimum therapeutic options, which can lead to poorer clinical outcomes. In this article, we review the current knowledge base and recent findings in the molecular landscape of NETs, focussing on the two most common forms: small intestinal and bronchopulmonary NETs.
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Berner AM, Pipinikas C, Ryan A, Dibra H, Moghul I, Webster A, Luong TV, Thirlwell C (2020). Diagnostic Approaches to Neuroendocrine Neoplasms of Unknown Primary Site.
Neuroendocrinology,
110(7-8), 563-573.
Abstract:
Diagnostic Approaches to Neuroendocrine Neoplasms of Unknown Primary Site.
Neuroendocrine neoplasms (NENs) arise from cells of neuronal and endocrine differentiation. While they are a rare entity, an increasing proportion of patients with NEN present with metastatic disease and no evident primary site using routine imaging or histopathology. NENs of unknown primary site have a poorer prognosis, often due to the challenge of selecting appropriate evidence-based management. We review the available literature and guidelines for the management of NENs of unknown primary site including clinical features, biochemical tests, histopathology, imaging, surgical exploration and localised and systemic treatments. We also discuss novel molecular techniques currently under investigation to aid primary site identification.
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Guerra-Assuncao JA, Conde L, Moghul I, Webster AP, Ecker S, Chervova O, Chatzipantsiou C, Prieto PP, Beck S, Herrero J, et al (2020). GenomeChronicler: the Personal Genome Project UK Genomic Report Generator Pipeline.
FRONTIERS IN GENETICS,
11 Author URL.
Dyke SOM, Saulnier KM, Dupras C, Webster AP, Maschke K, Rothstein M, Siebert R, Walter J, Beck S, Pastinen T, et al (2019). Points-to-consider on the return of results in epigenetic research.
GENOME MEDICINE,
11 Author URL.
Chervova O, Conde L, Guerra-Assuncao JA, Moghul I, Webster AP, Berner A, Cadieux EL, Tian Y, Voloshin V, Jesus TF, et al (2019). The Personal Genome Project-UK, an open access resource of human multi-omics data.
SCIENTIFIC DATA,
6 Author URL.
Steele CD, Tarabichi M, Oukrif D, Webster AP, Ye H, Fittall M, Lombard P, Martincorena I, Tarpey PS, Collord G, et al (2019). Undifferentiated Sarcomas Develop through Distinct Evolutionary Pathways.
CANCER CELL,
35(3), 441-+.
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Zheng SC, Webster AP, Dong D, Feber A, Graham DG, Sullivan R, Jevons S, Lovat LB, Beck S, Widschwendter M, et al (2018). A novel cell-type deconvolution algorithm reveals substantial contamination by immune cells in saliva, buccal and cervix.
EPIGENOMICS,
10(7), 925-940.
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Webster AP, Plant D, Ecker S, Zufferey F, Bell JT, Feber A, Paul DS, Beck S, Barton A, Williams FMK, et al (2018). Increased DNA methylation variability in rheumatoid arthritis-discordant monozygotic twins.
GENOME MEDICINE,
10 Author URL.
Tian Y, Morris TJ, Webster AP, Yang Z, Beck S, Feber A, Teschendorff AE (2017). ChAMP: updated methylation analysis pipeline for Illumina BeadChips.
BIOINFORMATICS,
33(24), 3982-3984.
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Webster AP, Smith SL, Worthington J, Barton A, Plant D (2016). Cryopreservation of cells does not substantially alter the DNA methylome of CD3+CD4+T cells.
SCANDINAVIAN JOURNAL OF RHEUMATOLOGY,
45(4), 329-330.
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Plant D, Webster A, Nair N, Oliver J, Smith SL, Eyre S, Hyrich KL, Wilson AG, Morgan AW, Isaacs JD, et al (2016). Differential Methylation as a Biomarker of Response to Etanercept in Patients with Rheumatoid Arthritis.
Arthritis Rheumatol,
68(6), 1353-1360.
Abstract:
Differential Methylation as a Biomarker of Response to Etanercept in Patients with Rheumatoid Arthritis.
OBJECTIVE: Biologic drug therapies represent a huge advance in the treatment of rheumatoid arthritis (RA). However, very good disease control is achieved in only 30% of patients, making identification of biomarkers of response a research priority. We undertook this study to test our hypothesis that differential DNA methylation patterns may provide biomarkers predictive of response to tumor necrosis factor inhibitor (TNFi) therapy in patients with RA. METHODS: an epigenome-wide association study was performed on pretreatment whole blood DNA from patients with RA. Patients who displayed good response (n = 36) or no response (n = 36) to etanercept therapy at 3 months were selected. Differentially methylated positions were identified using linear regression. Variance of methylation at differentially methylated positions was assessed for correlation with cis-acting single-nucleotide polymorphisms (SNPs). A replication experiment for prioritized SNPs was performed in an independent cohort of 1,204 RA patients. RESULTS: Five positions that were differentially methylated between responder groups were identified, with a false discovery rate of
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Webster A, Zufferey F, Plant D, Bell J, Barton A, Williams F, Worthington J (2015). 256. Altered DNA Methylation Associated with Rheumatoid Arthritis in Disease Discordant Monozygotic Twins. Rheumatology, 54(suppl_1), i149-i149.
Paul DS, Jones A, Sellar RS, Mayor NP, Feber A, Webster AP, Afonso N, Sergeant R, Szydlo RM, Apperley JF, et al (2015). A donor-specific epigenetic classifier for acute graft-versus-host disease severity in hematopoietic stem cell transplantation.
GENOME MEDICINE,
7 Author URL.
Oliver J, Plant D, Webster AP, Barton A (2015). Genetic and genomic markers of anti-TNF treatment response in rheumatoid arthritis.
BIOMARKERS IN MEDICINE,
9(6), 499-512.
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Webster A, Plant D, Eyre S, Flynn E, Martin P, Wilson G, Morgan AW, Isaacs J, Worthington J, Barton A, et al (2014). OP0051 Differential Methylation Related to Response to Etanercept in Patients with Rheumatoid Arthritis. Annals of the Rheumatic Diseases, 72(Suppl 3).
