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Dr Lucy Crooks BA, MA, PhD

Senior Lecturer in Genomics and Bioinformatics


Summary

I studied Natural Sciences at the University of Cambridge and gained a PhD at the University of Edinburgh. I have applied bioinformatics to research in diverse fields for eight years, including at the Sanger Institute. I also worked in diagnostic genetics in the NHS for two years. It is increasingly valuable to have bioinformatic skills as a biologist and genomics can make a huge impact on our understanding. The University recognises this, and my appointment is an investment into these areas. My research focus is analysing next generation sequencing data to identify genetic causes of disease.

About

I did my undergraduate in Natural Sciences at St John's College, Cambridge. I intended to read physics; the Natural Sciences course allowed me to see the opportunities for a theoretical approach in biology and began my enthusiasm for multidisciplinary work. I took Zoology in my final year. My PhD was supervised by Professor Andrew Read at the University of Edinburgh. I explored mathematical models of the course of malaria infections. The aim was to understand why the parasite might have higher fitness by putting less effort into transmission. 

My first postdoc was at ETH Zurich, Switzerland with Professor Sebastian Bonhoeffer. I looked at how protein mutations affected the fitness of HIV. We were testing whether mutations caused lower fitness when they occurred together than alone. This is a key point for one of the theories about the evolution of sexual recombination. An interaction between mutations in their effects is called epistasis.

I did a second postdoc at the Swedish University of Agricultural Sciences and Uppsala University with Professor Örjan Carlborg. I worked on methods for detecting quantitative trait loci (QTL) from animal breeding experiments. Quantitative trait loci are DNA regions, defined by molecular markers and usually containing many genes, that affect a quantitative trait (characteristics such as body weight that show a continuous range). I developed a framework for interpreting epistasis between QTL and applied it to a study of pig growth.

I returned to the UK as a statistical geneticist at the Wellcome Trust Sanger Institute. I worked with Professor Aarno Palotie and Dr Jeffrey Barrett. I was an analyst for the UK10K project, with responsibility for schizophrenia and autism cases. UK10K was one of the first large-scale human sequencing projects, and a substantial collaboration. The results are published in Nature. A considerable effort went into designing a process for quality control of next generation sequencing (NGS) data.

Following my postdocs, I became lead bioinformatician at Sheffield Diagnostic Genetics Service, part of Sheffield Children’s NHS Foundation Trust. My main role was to improve the computational set-up for NGS testing. The service does targeted sequencing on gene panels and the data need to be analysed quickly in order to meet patient turn-around-times. Important considerations for NGS in the NHS are sensitivity of mutation detection, validated protocols, data protection and data storage as patient information must be available for several years.

I started at Sheffield Hallam in March, 2016. I am designing a new module for the MSc in Biomedical Science: Human Genomics and Proteomics. I strongly believe that the best way to learn bioinformatics is in hands-on computer tutorials and this will be a core part of the module. My goal is to familiarise students with the computer skills that can make bioinformatics intimidating, and give them confidence to get involved in the analysis of their data.

Analysis of next generation sequencing (NGS) data
Prioritising NGS variants by their clinical relevance
Epistasis
Statistical and mathematical modelling

Teaching

Bioinformatics

BSc Biomedical Science
MSc Biomedical Science


Human Genomics and Proteomics
Bioinformatics and Human Genetics
Biomedical Laboratory Techniques
Professional and Scientific Practice 1
BSc and MSc Research Projects


Research

I am just starting up my research program. I am interested in projects with next generation sequencing data. I am especially interested in understanding the genetic basis of disease.

More details will follow soon.   

Publications

Journal articles

Crooks, L., Cooper-Knock, J., Heath, P.R., Bouhouche, A., Elfahime, M., Azzouz, M., ... Tazi-Ahnini, R. (2020). Identification of single nucleotide variants in the Moroccan population by whole-genome sequencing. BMC Genetics, 21 (1), 111. http://doi.org/10.1186/s12863-020-00917-4

Palubeckaitė, I., Crooks, L., Smith, D., Cole, L., Bram, H., Le Maitre, C., ... Cross, N.A. (2019). Mass spectrometry imaging of endogenous metabolites in response to doxorubicin in a novel 3D osteosarcoma cell culture model. Journal of Mass Spectrometry. http://doi.org/10.1002/jms.4461

Gorman, K.M., Meyer, E., Grozeva, D., Spinelli, E., McTague, A., Sanchis-Juan, A., ... Crooks, L. (2019). Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia. American Journal of Human Genetics, 104 (5), 948-956. http://doi.org/10.1016/j.ajhg.2019.03.005

Haworth, S., Shapland, C.Y., Hayward, C., Prins, B.P., Felix, J.F., Medina-Gomez, C., ... Jackson, D.K. (2019). Low-frequency variation in TP53 has large effects on head circumference and intracranial volume. Nature Communications, 10 (1). http://doi.org/10.1038/s41467-018-07863-x

Crooks, L., & Guo, Y. (2017). Consequences of epistasis on growth in an Erhualian x White Duroc pig cross. PLoS ONE, 12 (1), e0162045. http://doi.org/10.1371/journal.pone.0162045

Balasubramanian, M., Hurst, J., Brown, S., Bishop, N.J., Arundel, P., DeVile, C., ... Skerry, T.M. (2017). Compound heterozygous variants in NBAS as a cause of atypical osteogenesis imperfecta. Bone, 94, 65-74. http://doi.org/10.1016/j.bone.2016.10.023

Crooks, L., & Barrett, J.C. (2016). Rare loss-of-function variants in SETD1A are associated with schizophrenia and developmental disorders. Nature Neuroscience, 19, 571-577. http://doi.org/10.1038/nn.4267

Walter, K., Min, J.L., Huang, J., & Crooks, L. (2015). The UK10K project identifies rare variants in health and disease. Nature, 526 (7571), 82-90. http://doi.org/10.1038/nature14962

Huang, J., Howie, B., McCarthy, S., Memari, Y., Walter, K., Min, J.L., ... Jamshidi, Y. (2015). Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel. Nature Communications, 6. http://doi.org/10.1038/ncomms9111

Schmidts, M., Hou, Y., Cortés, C.R., Mans, D.A., Huber, C., Boldt, K., ... Kolb-Kokocinski, A. (2015). TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dystrophy with impaired retrograde intraflagellar transport. Nature Communications, 6. http://doi.org/10.1038/ncomms8074

Taylor, P.N., Porcu, E., Chew, S., Campbell, P.J., Traglia, M., Brown, S.J., ... Flyod, J. (2015). Whole-genome sequence-based analysis of thyroid function. Nature Communications, 6. http://doi.org/10.1038/ncomms6681

De Rubeis, S., He, X., Goldberg, A.P., Poultney, C.S., Samocha, K., Cicek, A.E., ... Buxbaum, J.D. (2014). Synaptic, transcriptional and chromatin genes disrupted in autism. Nature, 515 (7526), 209-215. http://doi.org/10.1038/nature13772

Timpson, N.J., Walter, K., Min, J.L., Tachmazidou, I., Malerba, G., Shin, S.Y., ... Hubbard, T. (2014). A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans. Nature Communications, 5. http://doi.org/10.1038/ncomms5871

Nelson, R.M., Nettelblad, C., Pettersson, E., Shen, X., Crooks, L., Besnier, F., ... Carlborg, O. (2013). MAPfastR: Quantitative trait loci mapping in outbred line crosses. G3: Genes, Genomes, Genetics, 3 (12), 2147-2149. http://doi.org/10.1534/g3.113.008623

Crooks, L., Carlborg, O., Marklund, S., & Johansson, A.M. (2013). Identification of null alleles and deletions from snp genotypes for an intercross between domestic and wild chickens. G3: Genes, Genomes, Genetics, 3 (8), 1253-1260. http://doi.org/10.1534/g3.113.006643

Ek, W., Sahlqvist, A.S., Crooks, L., Sgonc, R., Dietrich, H., Wick, G., ... Kerje, S. (2012). Corrigendum to ‘‘Mapping QTL affecting a systemic sclerosis-like disorder in a cross between UCD-200 and red jungle fowl chickens” [Dev. Comp. Immunol. 38(2) (2012) 352–359] (S0145305X12001346) (10.1016/j.dci.2012.06.006)). Developmental and Comparative Immunology, 38 (4), 561. http://doi.org/10.1016/j.dci.2012.09.003

Ek, W., Sahlqvist, A.S., Crooks, L., Sgonc, R., Dietrich, H., Wick, G., ... Kerje, S. (2012). Mapping QTL affecting a systemic sclerosis-like disorder in a cross between UCD-200 and red jungle fowl chickens. Developmental and Comparative Immunology, 38 (2), 352-359. http://doi.org/10.1016/j.dci.2012.06.006

Crooks, L., Nettelblad, C., & Carlborg, O. (2011). An improved method for estimating chromosomal line origin in QTL analysis of crosses between outbred lines. G3: Genes, Genomes, Genetics, 1 (1), 57-64. http://doi.org/10.1534/g3.111.000109

Conference papers

Nettelblad, C., Holmgren, S., Crooks, L., & Carlborg, O. (2009). cnF2freq: Efficient determination of genotype and haplotype probabilities in outbred populations using markov models. Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), 5462 LNBI, 307-319. http://doi.org/10.1007/978-3-642-00727-9_29

Other activities

I am a founding member of the Sheffield Bioinformatics Hub and an honorary lecturer at the University of Sheffield.
I am involved in teaching the MSc in Genomic Medicine at the University of Sheffield. 


Postgraduate supervision

2010-2011. Co-supervisor for final year. Genetic Analysis of Autoimmune and Metabolic Traits in Chickens.

2009-2015. Co-supervisor for part-time PhD. Submitted for and obtained a Licentiate. Genetic variance and covariance components for across population evaluation of Brown Swiss cattle.


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