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Professor Myles Lewis

Myles

Professor of Precision Medicine & Rheumatology

Centre: Experimental Medicine and Rheumatology

Email: myles.lewis@qmul.ac.uk
Telephone: +44(0) 20 7882 3305

Profile

ORCID iD: 0000-0001-9365-5345 

Myles Lewis studied preclinical medicine at Cambridge University, and clinical medicine at Oxford University. During his Rheumatology clinical training at multiple London teaching hospitals, he has worked extensively on Systemic Lupus Erythematosus (SLE) and other connective tissue diseases. He was awarded a Clinical Research Fellowship from the Wellcome Trust in 2005, for his PhD at the Hammersmith Hospital/Imperial College London, focused on understanding the causes of accelerated heart disease in SLE. In 2011 for his ongoing lab research on the role of ubiquitination in SLE and autoimmune disease, he was awarded a Clinician Scientist Fellowship by Arthritis Research UK. In 2015 he was awarded the Lancet Prize for Clinician Scientists at the Academy of Medical Sciences for his research on ubiquitination genes in SLE. 

Professor Lewis also heads up a bioinformatics/biostatistics group analysing and integrating multi-omic data across autoimmune rheumatic diseases (SLE, Sjogren’s syndrome and rheumatoid arthritis). He is a group leader within the biostatistics and bioinformatics analysis teams for several rheumatoid arthritis studies including the Pathobiology of Early Arthritis Cohort (PEAC), the R4RA biopsy-driven randomised clinical trial and the Stratification of Biologic Therapies for RA by Pathobiology study (STRAP). He is a member of the bioinformatic analysis team for several stratified medicine projects including MRC MATURA, MRC RA-MAP, IMID-Bio and the EU Innovative Medicines Initiative (IMI) programme 3TR. He is a Fellow of the Turing Institute and an Academic Fellow of the Digital Environment Research Institute at Queen Mary.

Research

Group members

Bioinformatics and biostatistics team: Cankut Çubuk, Katriona Goldmann, Giovanni Giorli, Elisabetta Sciacca, Anna Surace

Research staff (wet lab): Ilaria Esposito, Sotiria Manou-Stathopoulou, Yoanna Kontra, Chiara Giacomassi, Susan Wang

Former group members: Felice Rivellese, Daniele Mauro, Christopher Johns, Fabiola Bene, Lu Zou, Kevin Blighe, Sharmila Rana, Xiujuan Hou, Simon Vyse, Adrian Shields, Sebastian Boeltz

Bioinformatics and machine learning in stratified medicine
Professor Lewis leads a bioinformatics and biostatistics team involved in analysing and integrating multi-omic data including bulk & single cell RNA-Sequencing (RNA-Seq), genotype & expression Quantitative Trait Loci (eQTL) analysis, immunoglobulin repertoire analysis, CyTOF and protein microarray. Our group has interests in machine learning to predict clinical response for personalised/ stratified medicine, data visualisation of big data and disseminating results through interactive data web portals. Our group developed a number of R/shiny apps (https://peac.hpc.qmul.ac.uk/) to allow exploration of RNA-sequencing data on synovial biopsies from the Pathobiology of Early Arthritis Cohort (PEAC). This website allows researchers to directly compare synovium and blood genes and gene modules in early rheumatoid arthritis and see how gene expression correlates with clinical measures of disease activity and response to therapy, thus enabling in-depth interrogation of the data. In the R4RA clinical trial, our analysis of RNA-Seq data from synovial biopsies from this cohort showed that patients with low levels of B cell signature genes were less likely to respond to the B cell depleting agent rituximab in comparison to the IL-6 receptor inhibitor tocilizumab. 

Ubiquitination in autoimmune disease
My lab research involves understanding the effects of ubiquitination pathways on the immune system, and their impact on autoimmune rheumatic diseases especially SLE (lupus), rheumatoid arthritis (RA) and other connective tissue disorders. My research focuses on trying to understand how genetic variation in ubiquitination genes influences B cell differentiation and autoantibody production through regulation of the master transcription factor of inflammation, NF-kB, thus increasing susceptibility to lupus and autoimmune disease. Our work has important translational medical implications, since we aim to determine whether particular ubiquitination genes represent novel targets for new therapies to treat lupus, RA and other autoimmune diseases.

Software

Software packages in R and python published by Professor Lewis’s team include:

R packages available from CRAN

  • Spectrum performs fast self-tuning spectral clustering using an adaptive density aware spectral kernel.
  • volcano3D enables visualisation of 3-way analyses of gene expression and other high dimensional 3-class data using 3D volcano plots or polar plots.
  • glmmSeq enables analysis of longitudinal RNA-Seq and other omics data using mixed effect models which can either be negative binomial generalised linear mixed effects models (GLMM) which are suitable for RNA-Seq data or Gaussian linear mixed effects models (LMM). Analyses are parallelised for speed.
  • nestedcv implements nested k*l-fold cross-validation for lasso and elastic-net regularised linear models via the ‘glmnet’ package and many other machine learning models via the ‘caret’ package.
  • locuszoomr generates publication-ready regional gene locus plots similar to those produced by the web interface LocusZoom, but running locally in R. Genetic or genomic data with gene annotation tracks are plotted via R base graphics, 'ggplot2' or 'plotly', allowing flexibility and easy customisation including laying out multiple locus plots on the same page.
  • easylabel enables interactive labelling of scatter plots, volcano plots and Manhattan plots using a ‘shiny’ and ‘plotly’ interface. Users can hover over points to see where specific points are located and click points on/off to easily label them. Labels can be dragged around the plot to place them optimally.

R packages in Bioconductor

  • enhancedVolcano generates publication-ready volcano plots with enhanced colouring and labelling.
  • M3C performs Monte Carlo reference-based consensus clustering of high dimensional omics data.

R packages on GitHub

  • DEGGs tests for differential gene-gene correlations across different groups of samples in count data from high-throughput sequencing assays, leveraging gene-gene interaction graph network information.

Packages published in collaboration with other teams

  • shinyExprPortal is a visualisation tool which enables deployment of configuration file-based 'shiny' apps with minimal programming for interactive exploration and analysis showcase of molecular expression data.
  • MUSTANG – Multi Stain Graph Attention Multiple Instance Learning – a graph neural network pipeline for whole slide image (WSI) classification using multi-stain embeddings and self-attention graph pooling.
  • bbmix models RNA-seq reads using a mixture of 3 beta-binomial distributions to generate posterior probabilities for genotyping bi-allelic single nucleotide polymorphisms.

Publications

  • Lewis MJ, Spiliopoulou A, Goldmann K, Pitzalis C, McKeigue P, Barnes MR. nestedcv: an R package for fast implementation of nested cross-validation with embedded feature selection designed for transcriptomics and high dimensional data. Bioinform Adv 2023; 3(1): vbad048. PMID: 37113250
  • Henkin R, Goldmann K, Lewis MJ, Barnes MR. shinyExprPortal: a configurable 'shiny' portal for sharing analysis of molecular expression data. Bioinformatics 2024; 40(4): btae172. PMID: 38552327
  • Gallagher-Syed A, Rossi L, Rivellese F, Pitzalis C, Lewis MJ, Barnes M, Slabaugh G. MUSTANG: Multi-stain self-attention Graph Multiple Instance Learning pipeline for histopathology Whole Slide Images. British Machine Vision Conference 2023. arXiv:2309.10650
  • Gallagher-Syed A, Khan A, Rivellese F, Pitzalis C, Lewis MJ, Slabaugh G, Barnes MR. Automated segmentation of rheumatoid arthritis immunohistochemistry stained synovial tissue. Front Med Tech 2023 arXiv:2309.07255
  • Vigorito E, Barton A, Pitzalis C, Lewis MJ, Wallace C. BBmix: a Bayesian Beta-Binomial mixture model for accurate genotyping from RNA-sequencing. Bioinformatics 2023; btad393. PMID: 37338536
  • Sciacca E, Alaimo S, Silluzio G, Ferro F, Latora V, Pitzalis C, Pulvirenti A, Lewis MJ. DEGGs: an R package with shiny app for the identification of differentially expressed gene-gene interactions in high-throughput sequencing data. Bioinformatics 2023; 39(4): btad192. PMID: 37084249
  • John CR, Watson D, Barnes M, Pitzalis C, Lewis MJ. Spectrum: Fast density-aware spectral clustering for single and multi-omic data. Bioinformatics 2020; 36(4): 1159-66. PMID: 31501851
  • John CR, Watson D, Russ R, Goldmann K, Ehrenstein M, Pitzalis C, Lewis MJ, Barnes M. M3C: Monte Carlo reference-based consensus clustering. Sci Rep 2020; 10(1): 1816. PMID: 32020004

Publications

Full list of publications

  1. ** Rivellese F, Surace A, Goldmann K, Sciacca E, Cubuk C, Giorli G, John CR, Nerviani A, Fossati-Jimack L, Thorborn G, Manzoor A, Prediletto E, Church S, Hudson B, Warren S, McKeigue P, Humby F, Bombardieri M, Barnes MR, Lewis MJ*, Pitzalis C. Rituximab versus tocilizumab in rheumatoid arthritis: synovial biopsy-based biomarker analysis of the phase 4 R4RA randomized trial. Nature medicine 2022; 28(6): 1256-68. PMID: 35589854 *Co-senior author
  2. Lewis MJ, Pitzalis C. Progress continues in prediction of the response to treatment of RA. Nat Rev Rheum 2022. doi: 10.1038/s41584-022-00890-5. PMID: 36526946
  3. ** Humby F, Durez P, Buch MH, Lewis MJ, Rizvi H, Rivellese F, Nerviani A, Giorli G, Mahto A, Montecucco C, Lauwerys B, Ng N, Ho P, Bombardieri M, Romão VC, Verschueren P, Kelly S, Sainaghi PP, Gendi N, Dasgupta B, Cauli A, Reynolds P, Cañete JD, Moots R, Taylor P, Edwards CJ, Isaacs J, Sasieni P, Choy E, Pitzalis C. Rituximab versus Tocilizumab in anti-TNF inadequate responder patients with Rheumatoid Arthritis (R4RA): a stratified, biopsy-driven, multi-centre, randomised, open label, controlled clinical trial – 16 week outcomes. The Lancet 2021; 397(10271): 305-17. PMID: 33485455
  4. Nerviani A, Boutet MA, Tan WSG, Goldmann K, Purkayastha N, Lajtos T, Hands RE, Lewis MJ, Kelly S, Pitzalis C. IL-23 skin and joint profiling in psoriatic arthritis: novel perspectives in understanding clinical responses to IL-23 inhibitors. Ann Rheum Dis 2021; 80(5):591-597. PMID: 33243781
  5. Rivellese F, Manou-Stathopoulou S, Mauro D, Goldmann K, Pyne D, Rajakariah R, Gordon PA, Schafer P, Bombardieri M, Pitzalis C, Lewis MJ. Effects of targeting the transcription factors Ikaros and Aiolos on B cell activation and differentiation in Systemic Lupus Erythematosus. Lupus Sci Med 2021; 8(1): e000445. PMID: 33727237
  6. Gomez EA, Colas RA, Souza PR, Hands RE, Lewis MJ, Bessant C, Pitzalis C, Dalli J. Blood pro-resolving mediators are linked with synovial pathology and predictive of DMARD responsiveness in rheumatoid arthritis. Nature Communications 2020; 11(1): 5420. PMID: 33110080
  7. Cherlin S, Lewis MJ, Plant D, Nair N, Goldmann K, Tzanis E, Barnes MR, McKeigue P, Barrett JH, Pitzalis C, Barton A, MATURA Consortium, Cordell HJ. Investigation of genetically-regulated gene expression and response to treatment in rheumatoid arthritis highlights an association between IL18RAP expression and treatment response. Ann Rheum Dis 2020; 79(11): 1446-52. PMID: 32732242
  8. Alivernini S, MacDonald L, Elmesmari A, Finlay S, Tolusso B, Rita Gigante M, Petricca M, Di Mario C, Bui L, Perniola S, Attar M, Gessi M, Fedele AL, Filer A, McSharry C, Millar NL, Kirschner K, Nerviani A, Lewis MJ, Pitzalis C, Clark A, Ferraccioli G, Udalova I, Gremese E, McInnes IB, Otto TD, Kurowska-Stolarska M. Distinct tissue macrophage subsets provide a cellular and molecular mechanism for disease remission in rheumatoid arthritis. Nature Medicine 2020; 26(8):1295-1306. PMID: 32601335
  9. Rivellese F, Humby F, Bugatti S, Fossati-Jimack L, Rizvi H, Lucchesi D, Lliso-Ribera G, Nerviani A, Hands RE, Giorli G, Frias B, Thornborn G, Jaworska E, John CR, Goldmann K, Lewis MJ, Manzo A, Bombardieri M, Pitzalis C. B cell synovitis and clinical phenotypes in rheumatoid arthritis: relationship to disease stages and drug exposure. Arthritis Rheumatol 2020; 72(5): 714-25. PMID: 31785084
  10. John CR, Watson D, Russ R, Goldmann K, Ehrenstein M, Pitzalis C, Lewis MJ, Barnes M. M3C: Monte Carlo reference-based consensus clustering. Sci Rep 2020; 10(1): 1816. PMID: 32020004
  11. ** Lewis MJ, Barnes MR, Blighe K, Goldmann K, Rana S, Hackney J, Ramamoorthi N, John CR, Watson D, Kummerfeld S, Hands RE, Riahi S, Rocher-Ros V, Rivellese F, Humby F, Kelly S, Bombardieri M, Ng N, DiCicco M, van der Heijde D, Landewé R, van der Helm-van Mil A, Cauli A, McInnes IB, Buckley CD, Choy E, Taylor P, Townsend MJ, Pitzalis C. Molecular portraits of early rheumatoid arthritis identify clinical and treatment response phenotypes. Cell Reports 2019; 28(9): 2455-70. PMID: 31461658
  12. Pucino V, Certo M, Bulusu V, Cucchi D, Goldmann K, Pontarini E, Haas R, Smith J, Headland SE, Blighe K, Ruscica M, Humby F, Lewis MJ, Kamphorst JJ, Bombardieri M, Pitzalis C, Mauro C. Lactate Buildup at the Site of Chronic Inflammation Promotes Disease by Inducing CD4+ T Cell Metabolic Rewiring. Cell Metab 2019; 30(6): 1055-1074. PMID: 31708446
  13. Lliso-Ribera G, Humby F, Lewis MJ, Nerviani A, Mauro D, Rivellese F, Kelly S, Hands RE, Bene F, Ramamoorthi N, Hackney J, Cauli A, Choy E, Filer A, Taylor P, McInnes I, Townsend M, Pitzalis C. Synovial tissue signatures enhance clinical classification and prognostic/treatment response algorithms in early inflammatory arthritis and predict requirement for subsequent biologic therapy. Ann Rheum Dis 2019; 78(12): 1642-52. PMID: 31582377
  14. John CR, Watson D, Barnes M, Pitzalis C, Lewis MJ. Spectrum: Fast density-aware spectral clustering for single and multi-omic data. Bioinformatics 2020; 36(4): 1159-66. PMID: 31501851
  15. Twohig JP, Cardus Figueras A, Andrews R, Wiede F, Cossins BC, Derrac Soria A, Lewis MJ, Townsend MJ, Millrine D, Li J, Hill D, Uceda Fernandez J, Liu X, Szomolay B, Pepper CJ, Taylor PR, Pitzalis C, Tiganis T, Williams NM, Jones GW, Jones SA. Activation of naïve CD4+ T cells re-tunes STAT1 signaling to deliver unique cytokine responses in memory CD4+ T cells. Nat Immunol 2019; 20(4): 458-470. PMID: 30890796
  16. ** Humby F, Lewis MJ,* Ramamoorthi N, Hackney J, Barnes M, Bombardieri M, Setiadi F, Kelly S, Bene F, di Cicco M, Riahi S, Rocher-Ros V, Ng N, Hands RE, van der Heijde D, Landewé R, van der Helm-van Mil S, Cauli A, McInnes IB, Buckley CD, Choy E, Taylor P, Townsend MJ, Pitzalis C. Synovial cellular and molecular signatures in early rheumatoid arthritis stratify clinical response to csDMARD therapy and predict radiographic progression. Ann Rheum Dis 2019; 78(6): 761-772. PMID: 30878974 *Joint first author
  17. Hensor EMA, McKeigue P, Buch MH, Barrett JH, Nam JL, Freeston J, Colombo M, Spiliopoulou A, Agakov F, Kelly S, Lewis MJ, Ling SF, Viatte S, Verstappen SMM, Barton A, Pitzalis C, Emery P, IACON consortium, PEAC consortium, Conaghan PG, Morgan AW. Validity of a 2-component imaging-derived disease activity score (2C-DAS28) for improved assessment of synovitis in early rheumatoid arthritis. Rheumatology 2019; 58(8): 1400-9. PMID: 30824919
  18. Lewis MJ, Barnes MR. RNA sequencing and machine learning as molecular scalpels. Nat Rev Rheumatol 2018; 14: 388–390. PMID: 29752460
  19. ** Lewis MJ, McAndrew MB, Wheeler C, Workman N, Agashe P, Koopmann J, Uddin E, Morris DL, Zou L, Stark R, Anson J, Cope AP, Vyse TJ. Autoantibodies targeting TLR and SMAD pathways define new subgroups in Systemic Lupus Erythematosus. J Autoimmun 2018; 91: 1-12. PMID: 29576246
  20. Pullabhatla V, Roberts AL, Lewis MJ, Mauro D, Morris DL, Odhams CA, Tombleson P, Liljedahl U, Vyse S, Simpson MA, Sauer S, de Rinaldis E, Syvänen AC, Vyse TJ. De novo mutations implicate novel genes in Systemic Lupus Erythematosus. Hum Mol Genet 2018; 27(3): 421-9. PMID: 29177435
  21. Ursini F, Leporini C, Bene F, D'Angelo S, Mauro D, Russo E, De Sarro G, Olivieri I, Pitzalis C, Lewis M, Grembiale RD. Anti-TNF-alpha agents and endothelial function in rheumatoid arthritis: a systematic review and meta-analysis. Sci Rep 2017; 7(1): 5346. PMID: 28706194
  22. Bombardieri M, Lewis M, Pitzalis C. Ectopic lymphoid neogenesis in rheumatic autoimmune diseases. Nat Rev Rheumatol 2017; 13(3): 141-154. PMID: 28202919
  23. Lewis MJ, Jawad A. The effect of ethnicity and genetic ancestry on the epidemiology, clinical features and outcome of Systemic Lupus Erythematosus. Rheumatology 2017; 56: i67-i77. PMID: 27940583
  24. Lewis MJ, Vyse S, Shields AM, Zou L, Khamashta M, Gordon PA, Pitzalis C, Vyse TJ, D’Cruz DP. Improved monitoring of clinical response in Systemic Lupus Erythematosus by longitudinal trend in soluble vascular cell adhesion molecule-1. Arthritis Res Ther 2016; 18: 5. PMID: 26746423
  25. ** Lewis MJ, Vyse S, Shields AM, Boeltz S, Gordon PA, Spector TD, Lehner PJ, Walczak H, Vyse TJ. UBE2L3 polymorphism amplifies NF-kB activation and promotes plasma cell development linking linear ubiquitination to multiple autoimmune diseases. Am J Hum Genet 2015; 96(2): 221-34. PMID: 25640675
  26. Lewis MJ, Vyse TV. “Connective Tissue Disease” in Chapter “Genetics and the Environment” in Oxford Textbook of Rheumatology, 2013, 4th edition, Ed. Watts RA et al.
  27. ** Lewis MJ, Malik TH, Fossati-Jimeck L, Carassiti D, Cook HT, Haskard DO, Botto M. Combining lupus and hyperlipidaemia in mice reveals distinct roles for complement in glomerulonephritis and atherosclerosis. Arthritis Rheum 2012; 64(8): 2707-18. PMID: 22392450
  28. ** Lewis MJ, Malik TH, Ehrenstein MR, Boyle JJ, Botto M, Haskard DO. Immunoglobulin M is required for protection against atherosclerosis in low-density lipoprotein receptor-deficient mice. Circulation 2009; 120(5): 417-26. PMID: 19620499

Sponsors

Collaborators

Internal

Prof Costantino Pitzalis; Prof Michele Bombardieri; Prof Francesco Dell’Accio; Prof Shafaq Sikandar; Prof Michael Barnes; Dr Paul Pfeffer; Prof Jesmond Dalli; Dr Adam Brentnall; Prof Marta Korbonits; Prof Pedro Cutillas; Dr James Whiteford

External

Prof Anne Barton (Manchester); Prof Paul McKeigue (Edinburgh); Prof Heather Cordell (Newcastle); Prof Iain McInnes (Glasgow); Prof Simon Jones (Cardiff); Prof Tim Vyse (KCL); Prof Francesca Capon (KCL); Prof James Wason (Newcastle); Dr Rachael Bashford-Rogers (Oxford)

Industry

GSK; Celgene

Disclosures

Prof Lewis is a co-inventor on three patents which have been licensed to Exagen Inc, USA:

  • US20200399703 – Diagnostic and therapeutic methods for the treatment of rheumatoid arthritis (RA) (Genentech, QMUL – Pitzalis, Lewis, Townsend, Ramamoorthi, Hackney)
  • WO/2021/064371 / Application no. GB 1914079.7 – Method of predicting requirement of biologic therapy (QMUL – Pitzalis, Lewis, Humby)
  • WO/2022/157506 / Application no. GB 2100821.4 – Method for treating rheumatoid arthritis (QMUL – Pitzalis, Lewis)
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