Professor Val Gillet

MA (Cambridge); MSc (Sheffield); PhD (Sheffield)

Information School

Professor of Chemoinformatics

Head of School

A photo of Professor Val Gillet
v.gillet@sheffield.ac.uk
+44 114 222 2652

Full contact details

Professor Val Gillet
Information School
Regent Court (IS)
211 Portobello
Sheffield
S1 4DP
Profile

After completing a degree in Natural Sciences at Cambridge, I took a short term research post in the Department of Information Studies (as the Information School was then called) and contributed to the building of a database of generic chemical structures as found in the patent literature. This post fueled my interest in computing and I took the MSc in Information Science, returning to the generic structures project for my master’s dissertation and subsequent PhD - this time developing novel search algorithms to retrieve structural information from the database. I then moved to the Chemistry Department at Leeds University where I led a team working on de novo design (that is, the in-silico design of chemical compounds to fit a set of constraints such as a protein binding site) before returning to Sheffield in the mid-nineties and taking up an academic post.

University Responsibilities

  • Head of School 2012-2016 & 2019-
  • REF Coordinator 2017-
  • Deputy Director of Research 2017-
  • Director of Research 2010-2012
  • Member of School’s Strategy Group 2009-
  • Member of School Promotions Panel
  • Workload Allocation Model lead 2010-2016.
  • Programme Coordinator for the MSc (Res) in Chemoinformatics (formerly the MSc in Chemoinformatics) 2000-2010.
  • Departmental EPSRC DTG Coordinator.
  • Staff Review and Development Scheme reviewer.
  • School Research Ethics Coordinator 2008-2010.
  • Chair of Staff/Student Committee from 2004 to 2007.
  • School Representative on Teaching Affairs Committee, Pure Science, 1999-2004.
  • Editor of School Newsletter, 1999-2004.
Research interests

My research interests are focussed on the development and application of chemoinformatics techniques that are used primarily in the design of novel bioactive compounds. I have expertise in data mining and machine learning methods including multiobjective evolutionary algorithms, emerging pattern mining and graph theory. Particular application areas include virtual screening, the identification of structure-activity relationships, toxicity prediction, 3D similarity methods and the de novo design of novel compounds. I also have expertise in developing novel representation methods for chemical structures with recent areas including reduced graphs, spectral geometry, wavelet analysis and reaction vectors.

Much of my research has been carried out in collaboration with pharmaceutical and software companies including: AstraZeneca, Cambridge Crystallographic Data Centre, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutials, Lhasa Limited, Novartis Pharamceuticals, Pfizer Central Research (UK and US), Sanofi-Aventis and Unilever. I also have collaborators across the University including Dr Beining Chen in the Department of Chemistry, Prof Rob Harrison in the Department of Automatic Control and Systems Engineering, Prof Tanya Whitfield in Biomedical Sciences, Prof Jon Sayers in the Medical School and Dr Heather Mortiboys in SITraN (Sheffield Institute for Translational Neuroscience).

I am a member of the Chemoinformatics Research Group.

Publications

Books

  • Chowdhury G, Gillet V, McLeod J & Willett P (2018) Preface. RIS download Bibtex download
  • Lipkowitz KB, Gillet VJ & Cundari TR (2006) Reviews in Computational Chemistry: Preface. RIS download Bibtex download
  • (2006) Reviews in Computational Chemistry. John Wiley & Sons, Inc.. RIS download Bibtex download

Journal articles

Chapters

Conference proceedings papers

  • de Leon ADLV & Gillet V (2018) Phenotypic screening aided by multitask prediction methods. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, Vol. 256 RIS download Bibtex download
  • de Leon ADLV & Gillet V (2017) Using deep neural networks with heterogeneous chemical data to support phenotypic assay campaigns. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, Vol. 254 RIS download Bibtex download
  • Seddon M, Cosgrove D, Packer M & Gillet V (2017) Application of spectral and diffusion geometry descriptors to shape-based virtual screening. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, Vol. 253 RIS download Bibtex download
  • Seddon M, Cosgrove D, Packer M & Gillet V (2017) Spectral and diffusion geometry descriptions of molecular shape. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, Vol. 253 RIS download Bibtex download
  • Kannas C, Read W, Ruddock N, Fletcher M, Jackson T, Stevens R, Winter J, Willett P & Gillet V (2015) Multiobjective transformation based de novo design: A case study of surfactants. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, Vol. 250 RIS download Bibtex download
  • Valencia J, Chen B & Gillet V (2012) Searching putative targets in silico for anti-prion compounds. Abstracts of Papers of the American Chemical Society, Vol. 243 RIS download Bibtex download
  • Gan S, Gillet VJ, Gardiner EJ & Cosgrove DA (2012) Spectral clustering of chemical data: A Lanczos-based approach. Abstracts of Papers of the American Chemical Society, Vol. 243 RIS download Bibtex download
  • Gillet VJ, Allen B, Bodkin M, Chen B, Cole J, Hristozov D, Liebeschuetz J & Patel H (2012) De novo design of synthetically accessible compounds: Application to fragment-based drug design. Abstracts of Papers of the American Chemical Society, Vol. 243 RIS download Bibtex download
  • Gillet V (2011) Pharmacophore methods: Past, present, and future. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, Vol. 242 RIS download Bibtex download
  • Gillet V, Martin R, Gardiner E & Senger S (2010) Applications of wavelets in virtual screening. Abstracts of Papers of the American Chemical Society, Vol. 240 RIS download Bibtex download
  • Gillet VJ, Patel H, Bodkin M & Chen BN (2009) De novo design using reaction vectors: Application to library design. Abstracts of Papers of the American Chemical Society, Vol. 237 RIS download Bibtex download
  • Mott IP, Gedeck P & Gillet VJ (2009) Multiobjective approach to optimizing scoring functions for docking. Abstracts of Papers of the American Chemical Society, Vol. 237 RIS download Bibtex download
  • Cole JC, Gardiner EJ, Gillet VJ & Taylor R (2009) Development of test systems for pharmacophore elucidation. Abstracts of Papers of the American Chemical Society, Vol. 237 RIS download Bibtex download
  • Martin RL, Gardiner EJ, Gillet VJ & Senger S (2009) Wavelet compression of GRID fields for similarity searching and virtual screening. Abstracts of Papers of the American Chemical Society, Vol. 237 RIS download Bibtex download
  • Cosgrove DA, Gardiner EJ, Gillet VJ & Taylor R (2008) COMP 97-Combining clique-detection, MOGUL and MOGA for pharmacophore generation. Abstracts of Papers of the American Chemical Society, Vol. 235 RIS download Bibtex download
  • Patel Y, Gillet VJ, Willet P, Pastor J, Howe T & Oyarzabal J (2008) COMP 270-Assessment of additive/nonadditive effects in SAR: Implications in the drug discovery iterative process. Abstracts of Papers of the American Chemical Society, Vol. 235 RIS download Bibtex download
  • Patel H, Gillet VJ, Chen BN & Bodkin M (2008) CINF 53-Structure generation using reaction vectors. Abstracts of Papers of the American Chemical Society, Vol. 235 RIS download Bibtex download
  • Gillet VJ, Holliday J & Willett P (2008) CINF 72-Graduate training in chemoinformatics at the University of Sheffield. Abstracts of Papers of the American Chemical Society, Vol. 235 RIS download Bibtex download
  • Gillet VJ & Willett P (2008) CINF 32-Academic-industrial collaboration in chemoinformatics: Experiences from the UK. Abstracts of Papers of the American Chemical Society, Vol. 235 RIS download Bibtex download
  • Gillet VJ, Cottrell S & Taylor R (2006) Generation of multiple pharmacophore hypotheses using a multiobjective optimization algorithm. Abstracts of Papers of the American Chemical Society, Vol. 231 RIS download Bibtex download
  • Gillet VJ (2004) Virtual screening using reduced graphs.. Abstracts of Papers of the American Chemical Society, Vol. 228 (pp U362-U363) RIS download Bibtex download
  • Bayley MJ, Gillet VJ, Willett P, Bradshaw J & Green DVS (1999) Computational analysis of molecular diversity for drug discovery. Proceedings of the Annual International Conference on Computational Molecular Biology, RECOMB (pp 321-330) RIS download Bibtex download
  • Gillet VJ, Downs GM, Holliday JD, Lynch MF & Dethlefsen W (1993) Searching a Full Generics Database. Chemical Structures 2 (pp 87-103) RIS download Bibtex download
Research group

Current PhD students

  • Christina Founti: New machine learning methods for the analysis and modelling of pharmaceutical data
  • Gian Marco Ghiandoni: Reaction-based molecule design
  • Jess Stacey: Data Mining for Lead Optimisation
  • Moritz Walter: Understanding artificial intelligence models for toxicity prediction
  • James Webster: Decision-theoretic methods for de novo design

Completed PhD students

  • Matthew Seddon: Development of novel techniques for assessing bio-isosteric similarity of chemical fragments.
  • Sonny Gan: The application of spectral clustering in drug discovery.
  • Jorge Valencia Delgadillo: Multiobjective design of novel antiprion compounds.
  • James Wallace: Reaction network for De Novo design
  • Georgios Papadatos: Data Mining for Lead Optimisation
  • Yogendra Patel: The Prediction of Molecular Properties Using Similarity Searching and Free-Wilson Analysis
  • P Watson: Calculating the Knowledge-Based Similarity and Complementarity of Functional Groups based on their Non-Bonded Interactions
  • Edward Barker: Chemical Similarity Searching Using Reduced Graphs
  • Kristian Birchall: Reduced Graph Approaches to Analysing High- Throughput Screening Data
  • Simon Cottrell: Generation of Multiple Pharmacophore Hypotheses Using Multiobjective Optimisation Techniques
  • Sally Mardikian: The Application of Multiobjective Optimisation to Protein-Ligand Docking
  • Richard Martin: Wavelet Approximation of GRID Fields for Virtual Screening
  • Kirstin Moffat: Development Of Computational Methods For 3D Similarity And Structure-Based Design Techniques In Lead Optimisation
  • Hina Patel: Patient and Practitioner Understanding of Traditional and Western Medical Acupuncture in Practice: A Qualitative Study
  • Richard Sherhod: Development of a Data Mining Tool for the Identification of Toxicophores
  • Trudi Wright: Multiobjective Optimisation of Combinatorial Libraries
  • Tummala Reddy: Design, Synthesis and SAR Studies Of Pyridine Dicarbonitriles As Potential Prion Therapeutics
Grants

Research Projects

EPSRC CASE studentship with GSK

Engineering and Physical Sciences Research Council Principal Investigator £81,792 1 October 2015 48 months

BBSRC CASE studentship with Evotec (UK) Ltd.

Biotechnology and Biological Sciences Research Council Principal Investigator £98,212 1 October 2017 48 months

BBSRC CASE studentship

Biotechnology and Biological Sciences Research Council Principal Investigator £70,000 1 October 2015 36 months

Bio-renewable Formulation - 6 month extension

Unilever Principal Investigator £49,171 1 February 2015 12 months

Diagnostic and Drug Discovery Initiative for Alzheimer's Disease

European Commission Investigator £739,714 1 October 2014 48 months

Alzheimer's disease (AD) is the major cause of dementia which has no cure at the moment. The overall aim of the project is to create a long-term strategic partnership between Sheffield University (UK), Lisbon University (Portugal), Eli Lilly (UK) and Biofordrug (Italy) in order to develop chemical biology tools for better understanding the role of PrPC in AD and harnessing this understanding to develop novel chemical entities for diagnostic and therapeutics applications. Our proposed programme will lead to major increases in the knowledge and capacity of all consortium members, achieved through significant intersectoral exchange of personnel between the partners over the duration of the project (total 134 person months) and through temporary recruitment of 5 new experienced researchers (total 114 person months). The project will thus underpin a substantial programme of intersectoral knowledge transfer and research training and lead to significant innovation and advances in several areas of basic research as well as diagnostics and therapeutics development. These activities will strongly enhance EU standing and international competitiveness in this extremely challenging and increasingly important technological area.

Bio-renewable Formulation Information and Knowledge Management System

Technology Strategy Board Investigator £24,992 1 April 2014 24 months

Innovative ICT can play a crucial role in many innovation processes, but its potential is not always exploited in many industries. A route to innovation in formulated product industries is the exploitation of materials in what would otherwise be lost to waste streams from current manufacturing processes. This is exciting both in terms of realising additional value from manufacturing, but also in reduced utilisation of unsustainable material sources and exploitation of novel feedstocks for novel functional materials with new application benefits. This project will develop an information system based on highly innovative information technologies with the capability to rapidly identify the feedstock and functional material opportunities for formulated products, and demonstrate its value in rapid bio-derived surfactant discovery. It aims to support chemical using industries where environmental impact, sustainability and materials security are increasingly significant drivers of innovation alongside improved performance in formulated products.

Project partners are Unilever, British Sugar, Croda, Cybula, University of Manchester and University of Liverpool.

N8 Biohub Information and Knowledge Management System

Technology Strategy Board Investigator £131,128 1 October 2013 28 months

The overall aim of this project is to build, and demonstrate the value of, an information system (IS) to support the creation of a "Bio-Hub" centred on the N8 university group. The IS will demonstrate how functional ingredients from simple transformations of sustainable plant & waste feedstocks can be identified more quickly and recommend the best feedstocks for a particular function. It will address two big data problems using clever algorithms: semantic extraction of the available domain literature (terabytes) and optimised global search algorithms to explore the combinatorially large number of transformation products (up to petabytes). The innovations are in the creation of robust enough algorithms to run semi-automonously in an information system and in bringing these together with all the other components. The value will be demonstrated for specific feedstocks and applications, but the ICTs will be selected for simple extension to, and maintenance of, the overall information domain. Project partners are Unilever, British Sugar, Croda, Cybula and University of Manchester.

Targeted dual drug screening in patient tissue to identify new treatments for Parkinson's

Parkinsons UK Investigator £249,795 2 September 2013 36 months

The number of patients with Parkinson's disease (PD) will double by 2030. Almost all current treatments focus on replacing the brain chemical, dopamine, which is lost in the disease. These treatments are effective at masking the motor symptoms of PD but they lose effectiveness over time and cause troublesome side effects. There is a lack of treatments which slow or stop disease progression; so called disease modifying therapies which alter the underlying disease causing pathwas. To date drug screens have not proven effective at getting new drugs through discovery and safety testing into the clinic. Therefore alternative drug screening strategies should be explored. Drug re-positioning which identifies new activities/uses of currently licensed drugs has been successful in other diseases. The aim of this study is to design and carry out a re-positioning drug screen in order to identify lead drugs which (i) show beneficial effects on the two most important underlying pathways leading to cell death in PD patient tissue and (ii) are already clinically licensed. The project is being led by Dr. Heather Mortiboys in the Department of NeuroScience. My role is to provide Chemoinformatics support to enable the in silico design of a library of drug compounds for screening.

AstraZeneca Collaboration - Belief Theory

AstraZeneca Investigator £70,000 22 November 2010 14 months

This project is focused on developing probabilistic similarity searching methods for searching databases of chemical structures. The aim is to develop computational tools that will support the application of similarity searching methods within AstraZeneca workflows, including effective ways of combining different search methods.

Knowledge Transfer Project - Lhasa Ltd

Technology Strategy Board Principal Investigator £132,024 1 October 2010 24 months

Lhasa Ltd. is a not-for-profit software development company whose core business is the development of knowledge about the relationship between chemical structure and toxicity. The aim of the project is to develop data mining methods to automate the discovery of knowledge about chemical structure-toxicity relationships. Knowledge discovery is traditionally done by domain experts who manually examine data sets of chemical structures and their related toxicology, in a very time consuming process. New methods will be developed based on emerging pattern mining which can lead to signficant reductions in the time required to augment the knowledge base.

De Novo Design

Cambridge Crystallographic Data Centre Principal Investigator £120,576 1 April 2009 24 months

The project involved the development of an evolutionary algorithm for the de novo design of novel chemical compounds to fit a variety of constraints. The project was a collaboration with the Cambridge Crystallographic Data Centre and Eli Lilly that addressed a key challenge in de novo design, which is ensuring that the compounds that are designed are synthetically accessibility. This was achieved by deriving the the molecular transformations used to generate novel structure from a knowledge-base of reactions and is not limited by reaction type or complexity.

CCDC Pharmacophore Collaboration

Cambridge Crystallographic Data Centre Principal Investigator £66,192 1 July 2008 11 months

The project was a continuation of the "AstraZeneca Collaboration - Pharmacophores" project and involved the development of a new multiobjective optimisation method for pharmacophore identification from sets of active compounds. A pharmacophore describes the three-dimensional arrangement of chemical features required for a small molecule to bind to a receptor and the aim of this project was to deduce the pharmacophore from a series of active compounds in the absence of the structure of the receptor itself. This involves superposing the compounds so that their common features are overlaid.

AstraZeneca Collaboration - Pharmacophores

AstraZeneca Principal Investigator £74,512 1 January 2007 12 months

The project involved the development of a new multiobjective optimisation method for pharmacophore identification from sets of active compounds. A pharmacophore describes the three-dimensional arrangement of chemical features required for a small molecule to bind to a receptor and the aim of this project was to deduce the pharmacophore from a series of active compounds in the absence of the structure of the receptor itself. This involves superposing the compounds so that their common features are overlaid.

Sanofi-Sheffield collaboration

Sanofi-Aventis Investigator £92,421 1 January 2007 12 months

Array design for lead optimisation in pharmaceutical research

GlaxoSmithKline Principal Investigator £252,000 23 October 2006 48 months

This EPSRC-funded project focused on the development of tools to assist medicinal chemists in the design of compound arrays during the lead optimisation stage of drug discovery. Lead optimisation is a complex, time-consuming task, in which chemists seek to obtain a promising balance among potency, off-target interactions, toxicity, and pharmacokinetic behaviour, to identify a candidate molecule to progress to clinical trials. The focus has been on inverse QSAR, that is, determining the structural change necessary to achieve a desired change in property. This has been approached through retrospective studies of lead optimisation projects within the GSK archive and the development of computational tools that can be applied in prospective array design to inform decision making by chemists. These included a novel context-sensitive approach to matched molecular-pairs analysis.

Novartis KTP

Knowledge Transfer Partnership Principal Investigator £143,754 1 May 2006 36 months

The project involved the development of multiobjective optimisation methods to improve the accuracy with which predictions can be made about the properties of molecules in the early stages of the drug discovery process. The project focused on protein-ligand docking which is a technique that is widely used to prioritise compounds for biological testing but which is limited in its effectiveness due to inadequacies in the scoring functions that are used to drive the procedure. Several of the known limitations of scoring functions were investigated including: the prediction of the binding-pose of a known ligand; the docking of ligands to non-native proteins; and the re-ranking of a dataset of ligands to correlate more closely with known binding affinities.

Janssen MSc Summer Placement

Janssen-Cilag Spain Principal Investigator £1,500 5 May 2005 4 months

Analysis of ADMET models

Janssen-Cilag Spain Principal Investigator £1,500 15 June 2004 15 months

Support tools for automatic pharmacophore generation

Pfizer Principal Investigator £71,467 1 March 2004 22 months

Johnson and Johnson PhD

Janssen Pharmaceuticals N.V. Investigator £76,305 1 January 2004 36 months

Tuning Parameters for Multiobjective Library Design

GlaxoSmithKline Principal Investigator £4,277 1 December 2003 2 months

Novel methods for the association of chemical similarity with biological response

GlaxoSmithKline Principal Investigator £21,000 1 October 2003 36 months

Mining molecular bioassay data

GlaxoSmithKline Principal Investigator £21,000 1 October 2002 36 months

The development of computational methods for 3D similarity and structure-based design techniques in lead optimisation

Pfizer Investigator £125,016 1 January 2003 24 months

Novel methods for the alignment of flexible molecules

GlaxoSmithKline Principal Investigator £21,000 1 October 2002 36 months

Multiple flexible alignment of molecules

Cambridge Crystallographic Data Centre Principal Investigator £19,500 1 May 2002 36 months
Teaching interests

My teaching interests are in applied computational techniques including data mining and machine learning. I played a central role in the curriculum design of the MSc Data Science which was launched in the School in September 2014 and currently I coordinate the module INF6028: Data Mining and Data Visualisation as well as supervising dissertations in data science.

I have a particular interest in applying data science techniques to the processing of chemical structures for applications such as drug design: a field which has become known as Chemoinformatics. I teach INF105: Introduction to Chemoinformatics and INF215: Introduction to Computer Aided Drug Design to first and second year chemistry undergraduates, respectively. I organised and ran an annual short course on a Practical Introduction to Chemoinformatics for many years which attracted PhD students and industrial delegates from across the globe.