Dr Valentina Cipriani

Profile

I hold a Degree in ‘Statistics’ (Sapienza University, Rome, 2004) and a PhD in ‘Public Health and Education’ (University of Pavia, Italy, 2009; including 2-year visiting PhD student at Prof. Balding's group, Imperial College London), with a thesis on meta-analytic methods for family-based genetic association studies. 

A successful post-doc (2009-2012) at the UCL Institute of Ophthalmology (London) with the publication of the first genome-wide association study (GWAS) of age-related macular degeneration (AMD) in the UK (Cipriani et al., HMG, 2012) led me to be recognised as an expert in the complex genetics of AMD both in the UK and internationally. I have been an active analyst of the International AMD Genomics Consortium (IAMDGC) with several other high-impact publications (see publication list).

I was then funded through a 5-year NIHR-BRC grant (2012-2017) as the referent genetic statistician at Moorfields Eye Hospital and the UCL Institute of Ophthalmology, where I expanded my research activities beyond complex genetics into rare disease diagnostics and gene discovery, and built a solid network of collaborators that landed my current affiliation at QMUL, first as a ‘Senior Bioinformatics Research Fellow’ (2017-2020, Prof. Smedley’s group), then as a faculty member ('Lecturer' in Statistical Genomics [March 2020 -July 2022], progressing to ‘Senior Lecturer’ in August 2022).

I am a member of the Centre for Translational Bioinformatics.
Twitter: @QMUL_C4TB.

I am a Fellow at the Queen Mary's Digital Environment Research Institute (DERI) (August 2022 - present).

Research

Group members

• Miss Apoorva Sarah Perepogu (MSc in Bioinformatics student, 2022-2023); project title: “Extending the rare variant burden analysis to the non-coding genome with an application to the 100,000 Genomes Project data”
• Miss Amy Evans (Barts charity PhD student, 2023- ); project title: “Genetic determinants of pituitary adenomas”

Contact me at v.cipriani@qmul.ac.uk or check out my Twitter account @Val3Cipriani for currently available PhD student and post-doc research positions.

Alumni

• Miss Catherine Kelly (MSc in Bioinformatics, 2020-2021); Kelly C, …Cipriani V, Phenotype-aware prioritisation of rare Mendelian disease variants. Trends Genet, 38:1271-1283, 2022
• Miss Penpitcha Thawong (MSc in Bioinformatics, 2018-2019); Cipriani V, …, Thawong P, et al. An Improved Phenotype-Driven Tool for Rare Mendelian Variant Prioritization: Benchmarking Exomiser on Real Patient Whole-Exome Data. Genes, 11:460, 2020
  

Summary

My research aims to help elucidate the genetic determinants of both common complex and rare Mendelian human diseases by using cutting-edge computational tools in genotyping and sequencing association studies. The divide between common and rare diseases has been decreasing over the past years with many common disorders presenting with their closely linked monogenic familial forms, as well as many Mendelian disorders showing incomplete penetrance and variable expressivity due, for example, to the effect of modifier genes and/or environmental factors.

I am currently involved in many national and international human genetic projects, including studies of the complex genetics of age-related macular degeneration (AMD) and the analysis of genomic data from the 100,000 Genomes Project (100KGP) and the University College London (UCL) exome consortium (UCLex).

My research output has a high clinical impact with potential implications for novel therapeutics in complex genetics and demonstrated increases in the diagnostic yield in rare diseases.

Exomiser; rare disease diagnostics and gene discovery
I have been an active member of the Monarch Initiative and Human Phenotype Ontology community, contributing to the improvement and assessment of flagship Exomiser tool for phenotype-based variant prioritisation. Such tools often lack extensive validation on real patient data. I have recently shown an effective Exomiser performance on a large rare disease whole-exome patient dataset (Cipriani et al., Genes, 2020) and supervised an in-depth review of phenotype-based variant prioritisation tools (Kelly et al., Trends Genet, 2022). Furthermore, I co-led the application of an Exomiser-based gene burden analysis pipeline to the pilot phase of the 100KGP pilot (Smedley&Smith&Martin&Thomas&McDonagh&Cipriani&Ellingford&Arno&Tucci& Vandrovcova&Chan&Williams et al., NEJM, 2021) that has already resulted in three confirmed gene discoveries (including Bourinaris&Smedley&Cipriani et al., EJHG, 2020) as well as new gene discoveries (Park&Tucci&Cipriani et al., Genet Med, 2022).

Family-based genetic association analyses
I have recently led a comprehensive analysis that used a combination of haplotype-sharing, genotyping and sequencing family-based methods and successfully identified non-coding SNVs and duplications in 13 families affected by rare autosomal dominant North Carolina macular dystrophy (NCMD) (Cipriani et al., Sci Rep, 2017). This was a long-awaited result, with the chromosome 5 linkage region for this disorder being known for 15 years. These results have recently triggered further studies that gained insights into the cis-regulatory mechanisms of NCMD and support that NCMD is a retinal enhanceropathy (Van de Sompele et al., bioRxiv 2022.03.08.481329, 2022).

Complex genetics of age-related macular degeneration
I was the leading statistician for the first genome-wide association study (GWAS) of AMD in the UK (Cipriani et al., HMG, 2012). The study allowed me to become a member of the International AMD Genomics Consortium (IAMDGC). The IAMDGC performed the largest GWAS of AMD with the discovery of 16 novel risk loci. I presented the corresponding findings at the 64^th ASHG meeting (San Diego, 2014) and contributed to the last IAMDGC GWAS manuscript (Fritsche et al., Nat Genet, 2016). Building on this experience, I have been pursuing a much-needed dissection of the well-established AMD-association at the CFH locus (known since 2005) with national and international experts in AMD and the complement system. I have led a wealth of statistical genetic data analyses that brought to the identification of FHR proteins as major players in AMD pathogenesis with concrete potential implications for complement inhibiting therapeutics (e.g., Complement Therapeutics Limited, CTx) (Cipriani et al, AJHG, 2021; Cipriani et al, Nat Commun, 2020).

I am a Senior Editor for the Annals of Human Genetics.

Publications

Google scholar statistics (as of June 2023), Citations: 5134; h-index: 23; i10-index: 31

• Leong IUS, Cabrera CP, Cipriani V et al. (2024). Large-Scale Pharmacogenomics Analysis of Patients With Cancer Within the 100,000 Genomes Project Combining Whole-Genome Sequencing and Medical Records to Inform Clinical Practice.. nameOfConference

  
  

  DOI: 10.1200/jco.23.02761

  
  

  QMRO: qmroHref
• Benkirane M, Bonhomme M, Morsy H et al. (2024). De novo and inherited monoallelic variants in TUBA4A cause ataxia and spasticity. nameOfConference

  
  

  DOI: 10.1093/brain/awae193

  
  

  QMRO: https://qmro.qmul.ac.uk/xmlui/handle/123456789/100459
• Pavinato L, Stanic J, Barzasi M et al. (2023). Missense variants in RPH3A cause defects in excitatory synaptic function and are associated with a clinically variable neurodevelopmental disorder. nameOfConference

  
  

  DOI: 10.1016/j.gim.2023.100922

  
  

  QMRO: qmroHref
• Chen Z, Tucci A, Cipriani V et al. (2023). Functional genomics provide key insights to improve the diagnostic yield of hereditary ataxia. nameOfConference

  
  

  DOI: 10.1093/brain/awad009

  
  

  QMRO: https://qmro.qmul.ac.uk/xmlui/handle/123456789/89472
• Morsy H, Benkirane M, Cali E et al. (2023). Expanding SPTAN1 monoallelic variant associated disorders: From epileptic encephalopathy to pure spastic paraplegia and ataxia. nameOfConference

  
  

  DOI: 10.1016/j.gim.2022.09.013

  
  

  QMRO: qmroHref
• Park J, Tucci A, Cipriani V et al. (2022). Heterozygous UCHL1 loss-of-function variants cause a neurodegenerative disorder with spasticity, ataxia, neuropathy, and optic atrophy. nameOfConference

  
  

  DOI: 10.1016/j.gim.2022.07.006

  
  

  QMRO: https://qmro.qmul.ac.uk/xmlui/handle/123456789/89469
• Kelly C, Szabo A, Pontikos N et al. (2022). Phenotype-aware prioritisation of rare Mendelian disease variants. nameOfConference

  
  

  DOI: 10.1016/j.tig.2022.07.002

  
  

  QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/84818
• Chen Z, Cipriani V, Zhang D et al. (2022). 022  Functional genomics and transcriptomics further characterise and potentially improve diagnostic yield of hereditary ataxias. nameOfConference

  
  

  DOI: 10.1136/jnnp-2022-abn.347

  
  

  QMRO: qmroHref
• Jacobsen JOB, Kelly C, Cipriani V et al. (2022). Evaluation of phenotype-driven gene prioritization methods for Mendelian diseases. nameOfConference

  
  

  DOI: 10.1093/bib/bbac188

  
  

  QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/84820
• Jacobsen JOB, Kelly C, Cipriani V et al. (2022). Phenotype‐driven approaches to enhance variant prioritization and diagnosis of rare disease. nameOfConference

  
  

  DOI: 10.1002/humu.24380

  
  

  QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/82621

Collaborators

Internal

• Professor Sir Mark Caulfield
• Professor Marta Korbonits

External

• Prof. Peter Robinson (JAX, USA)
• Dr. Richard Unwin (University of Manchester)
• Prof. Simon Clark (Tübingen University, Germany)
• Dr. Nikolas Pontikos (UCL)
• Prof. Reecha Sofat (UCL)
• Prof. Andrew Webster (UCL)
• Dr. Amanda Carr (UCL)
• Dr. Arianna Tucci (MRC Fellow, Genomics England)
• Prof. Mina Ryten (UCL)
• Prof. Giorgia Girotto (IRCCS Burlo Garofolo, Italy)

News

• Macular degeneration: Link found in eye disease treatment, February 2020