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MRC Toxicology Unit

 

The Bioinformatics group provides comprehensive and integrated informatics and computational analysis for the Unit Programmes and external collaborative projects.

Advanced informatics analysis is carried out on large data sets generated for the Unit’s programmes. Analysis of Next Generating Sequence and microarray data is carried out using commercial, open-source, and in-house developed software. The group members research and develop novel bioinformatic tools, algorithms, statistical data mining tools and software to fully support the Unit's systems approach to understanding mechanisms of Toxicity.  Major areas covered include:

1. Statistical data mining of biological and chemical databases.

2. Statistical analysis and validation of in vitro data with clinical datasets.

3. Statistical analysis to identify genomic biomarkers for drug sensitivity and resistance.

4. Ribosome profiling and RNA-seq.

5. Differential gene expression and translation.

6. Functional enrichment analysis of UTR motifs and GO terms and pathway analysis.

 

Selected publications

CD40L/IL-4–stimulated CLL demonstrates variation in translational regulation of DNA damage response genes including ATM

Lezina, L., Spriggs, R.V., Beck, D., Jones, C., Dudek, K.M., Bzura, A., Jones, G.D.D., Packham, G., Willis, A.E. & Wagner, S.D.

2018, Blood Advances, 2, 1869-1881.

An improved analysis methodology for translational profiling by microarray

Sbarrato, T., Spriggs, R.V., Wilson, L., Jones, C., Dudek, K., Bastide, A., Pichon, X., Pöyry, T. & Willis, A.E.

2017, RNA, 23, 1601-1613.

RTN3 is a novel cold-induced protein and mediates neuroprotective effects of RBM3

Bastide, A., Peretti, D., Knight, J.R.P., Grosso, S., Spriggs, R.V., Pichon, X., Sbarrato, T., Roobol, A., Roobol, J., Vito, D., Bushell, M., von der Haar, T., Smales, C.M., Mallucci, G.R., & Willis, A.E.

2017, Current Biology, 27(5), 638–650.

A ribosome related signature in peripheral blood CLL B cells is linked to reduced survival following treatment

Sbarrato, T., Horvilleur, E., Poyry, T., Hill, K., Chaplin, L.C., Spriggs, R.V., Stoneley, M., Wilson, L., Jayne, S., Vulliamy, T., Beck, D., Dokal, I., Dyer, M.J.S., Yeomans, A.M., Packham, G., Bushell, M., Wagner, S.D. & Willis, A.E.

2016, Cell Death and Disease, 7, e2249.

Molecular profiling reveals primary mesothelioma cell lines recapitulate human disease.

Chernova T, Sun XM, Powley IR, Galavotti S, Grosso S, Murphy FA, Miles GJ, Cresswell L, Antonov AV, Bennett J, Nakas A, Dinsdale D, Cain K, Bushell M, Willis AE, MacFarlane M.

Cell Death Differ. 2016 Feb 19. doi: 10.1038/cdd.2015.165.

Evaluating bias-reducing protocols for RNA sequencing library preparation.

Jackson TJ, Spriggs RV, Burgoyne NJ, Jones C, Willis AE.

BMC Genomics. 2014 Jul 7;15(1):569. doi: 10.1186/1471-2164-15-569.

A role for eukaryotic initiation factor 4B overexpression in the pathogenesis of diffuse large B-cell lymphoma.

Horvilleur E, Sbarrato T, Hill K, Spriggs RV, Screen M, Goodrem PJ, Sawicka K, Chaplin LC, Touriol C, Packham G, Potter KN, Dirnhofer S, Tzankov A, Dyer MJ, Bushell M, Macfarlane M, Willis AE.

Leukemia. 2014 May;28(5):1092-102. doi: 10.1038/leu.2013.295.

p63 transcriptionally regulates the expression of matrix metallopeptidase 13.

Celardo I, Antonov A, Amelio I, Annicchiarico-Petruzzelli M, Melino G.

Oncotarget. 2014 Mar 15;5(5):1279-89.

Large scale integration of drug-target information reveals poly-pharmacological drug action mechanisms in tumor cell line growth inhibition assays.

Knight RA, Gostev M, Ilisavskii S, Willis AE, Melino G, Antonov AV.

Oncotarget. 2014 Feb 15;5(3):659-66.

Rapamycin regulates biochemical metabolites.

Tucci P, Porta G, Agostini M, Antonov A, Garabadgiu AV, Melino G, Willis AE.

Cell Cycle. 2013 Aug 1;12(15):2454-67. doi: 10.4161/cc.25450.

Translational repression and eIF4A2 activity are critical for microRNA-mediated gene regulation.

Meijer HA, Kong YW, Lu WT, Wilczynska A, Spriggs RV, Robinson SW, Godfrey JD, Willis AE, Bushell M.

Science. 2013 Apr 5;340(6128):82-5. doi: 10.1126/science.1231197.