Claudia Calabrese

Claudia Calabrese
University of Cambridge | Cam · Department of Clinical Neurosciences

PhD Human Genetics

About

43
Publications
11,311
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Introduction
Claudia Calabrese currently works at the Department of Clinical Neurosciences, University of Cambridge. Claudia does research in Genetics, Molecular Biology and Evolutionary Biology. Her current projects are focussed on studying the role of mitochondrial common and rare variation (and mitochondrial heteroplasmy) in human complex diseases.
Additional affiliations
May 2017 - present
University of Cambridge
Position
  • Postodc
October 2015 - May 2017
EMBL-EBI
Position
  • PostDoc Position
January 2015 - October 2015
University of Bologna
Position
  • PostDoc Position

Publications

Publications (43)
Article
Full-text available
Motivation: The increasing availability of mitochondria-targeted and off-targeted sequencing data in Whole Exome and Genome Sequencing studies (WXS and WGS) has risen the demand of effective pipelines to accurately measure heteroplasmy and to easily recognize the most functionally important mitochondrial variants among a huge number of candidates....
Article
Full-text available
Background: Whole Exome Sequencing (WES) is one of the most used and cost-effective next generation technologies that allows sequencing of all nuclear exons. Off-target regions may be captured if they present high sequence similarity with baits. Bioinformatics tools have been optimized to retrieve a large amount of WES off-target mitochondrial DNA...
Article
Full-text available
Recent studies have demonstrated an unexpected complexity of transcription in eukaryotes. The majority of the genome is transcribed and only a little fraction of these transcripts is annotated as protein coding genes and their splice variants. Indeed, most transcripts are the result of antisense, overlapping and non-coding RNA expression. In this f...
Article
Full-text available
Background Glioblastoma multiforme (GBM) is the most malignant brain tumor in adults, but its etiology still remains unknown. Recently, a role of viruses such as cytomegalovirus and JC virus in gliomagenesis has been suggested. Since human papillomavirus (HPV) is considered the most common oncogenic virus in humans, we evaluated its occurrence in G...
Article
Full-text available
Background Aerobic glycolysis, namely the Warburg effect, is the main hallmark of cancer cells. Mitochondrial respiratory dysfunction has been proposed to be one of the major causes for such glycolytic shift. This hypothesis has been revisited as tumors appear to undergo waves of gene regulation during progression, some of which rely on functional...
Article
Full-text available
Mitochondria are implicated in the pathogenesis of cardiovascular diseases (CVDs) but the reasons for this are not well understood. Maternally-inherited population variants of mitochondrial DNA (mtDNA) which affect all mtDNA molecules (homoplasmic) are associated with cardiometabolic traits and the risk of developing cardiovascular disease. However...
Article
Full-text available
Methylation on CpG residues is one of the most important epigenetic modifications of nuclear DNA, regulating gene expression. Methylation of mitochondrial DNA (mtDNA) has been studied using whole genome bisulfite sequencing (WGBS), but recent evidence has uncovered technical issues which introduce a potential bias during methylation quantification....
Article
Full-text available
Objective To determine whether whole genome sequencing can be used to define the molecular basis of suspected mitochondrial disease. Design Cohort study. Setting National Health Service, England, including secondary and tertiary care. Participants 345 patients with suspected mitochondrial disorders recruited to the 100 000 Genomes Project in Eng...
Article
Full-text available
Mitochondrial DNA (mtDNA) variants influence the risk of late-onset human diseases, but the reasons for this are poorly understood. Undertaking a hypothesis-free analysis of 5,689 blood-derived biomarkers with mtDNA variants in 16,220 healthy donors, here we show that variants defining mtDNA haplogroups Uk and H4 modulate the level of circulating N...
Article
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Mitochondrial DNA (mtDNA) variation in common diseases has been underexplored, partly due to a lack of genotype calling and quality-control procedures. Developing an at-scale workflow for mtDNA variant analyses, we show correlations between nuclear and mitochondrial genomic structures within subpopulations of Great Britain and establish a UK Bioban...
Preprint
Full-text available
Methylation on CpG residues is one of the most important epigenetic modifications of nuclear DNA, regulating gene expression. Methylation of mitochondrial DNA (mtDNA) has been studied using whole genome bisulfite sequencing (WGBS), but recent evidence has uncovered major technical issues which introduce a potential bias during methylation quantific...
Article
Full-text available
Reversible infantile respiratory chain deficiency (RIRCD) is a rare mitochondrial myopathy leading to severe metabolic disturbances in infants, which recover spontaneously after 6‐months of age. RIRCD is associated with the homoplasmic m.14674T>C mitochondrial DNA mutation; however, only ~ 1/100 carriers develop the disease. We studied 27 affected...
Article
Reversible infantile respiratory chain deficiency (RIRCD) is a rare mitochondrial myopathy leading to severe metabolic disturbances in infants, which recover spontaneously after 6-months of age. RIRCD is associated with the homoplasmic m.14674T>C mitochondrial DNA mutation; however, only ~ 1/100 carriers develop the disease. We studied 27 affected...
Preprint
Full-text available
Reversible infantile respiratory chain deficiency (RIRCD) is a rare mitochondrial myopathy leading to severe metabolic disturbances in infants, which recover spontaneously after 6 months of age. RIRCD is associated with the homoplasmic m.14674T>C mitochondrial DNA mutation, however only ∼1/100 carriers develop the disease. We studied 27 affected an...
Article
Full-text available
Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG...
Article
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Transcript alterations often result from somatic changes in cancer genomes¹. Various forms of RNA alterations have been described in cancer, including overexpression², altered splicing³ and gene fusions⁴; however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relativ...
Chapter
Detection of human mitochondrial DNA variants and quantification of heteroplasmy have quickly evolved since the discovery of the mitochondrial genome in the early 1960s. Traditionally, mitochondrial variants were studied through a combination of molecular biology techniques, often limited to the analysis of single variants. The development of Sange...
Article
Most human protein-coding genes are regulated by multiple, distinct promoters, suggesting that the choice of promoter is as important as its level of transcriptional activity. However, while a global change in transcription is recognized as a defining feature of cancer, the contribution of alternative promoters still remains largely unexplored. Her...
Preprint
Full-text available
Most human protein-coding genes are regulated by multiple, distinct promoters, suggesting that the choice of promoter is as important as its level of transcriptional activity. While the role of promoters as driver elements in cancer has been recognized, the contribution of alternative promoters to regulation of the cancer transcriptome remains larg...
Preprint
Full-text available
We present the most comprehensive catalogue of cancer-associated gene alterations through characterization of tumor transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes project. Using matched whole-genome sequencing data, we attributed RNA alterations to germline and somatic DNA alterations, revealing likely genetic mechanis...
Preprint
Full-text available
Cancer is characterised by somatic genetic variation, but the effect of the majority of non-coding somatic variants and the interface with the germline genome are still unknown. We analysed the whole genome and RNA-Seq data from 1,188 human cancer patients as provided by the Pan-cancer Analysis of Whole Genomes (PCAWG) project to map cis expression...
Preprint
Full-text available
Cancers develop through somatic mutagenesis, however germline genetic variation can markedly contribute to tumorigenesis via diverse mechanisms. We discovered and phased 88 million germline single nucleotide variants, short insertions/deletions, and large structural variants in whole genomes from 2,642 cancer patients, and employed this genomic res...
Article
Whole-exome sequencing studies have transformed our understanding of recurrent somatic mutations that contribute to cancer pathogenesis; however, these studies limit our ability to identify cancer-associated mutations to those that cause protein-coding changes. To more comprehensively catalogue cancer-associated gene alterations, we have extensivel...
Article
Introduction: We present a novel method to identify cancer driver genes that jointly examines any number of diverse transcriptomic alterations with the goal to uncover highly recurrent and heterogeneous patterns in 1190 samples across 26 cancer types as part of the PanCancer Analysis of Whole Genomes (PCAWG) of the International Cancer Genome Conso...
Article
Full-text available
The HmtDB resource hosts a database of human mitochondrial genome sequences from individuals with healthy and disease phenotypes. The database is intended to support both population geneticists as well as clinicians undertaking the task to assess the pathogenicity of specific mtDNA mutations. The wide application of next-generation sequencing (NGS)...
Article
Full-text available
Assigning a pathogenic role to mitochondrial DNA (mtDNA) variants and unveiling the potential involvement of the mitochondrial genome in diseases are challenging tasks in human medicine. Assuming that rare variants are more likely to be damaging, we designed a phylogeny-based prioritization workflow to obtain a reliable pool of candidate variants f...
Article
Oncocytic change is the result of aberrant mitochondrial hyperplasia, which may occur in both neoplastic and non-neoplastic cells and is not infrequent in the thyroid. Despite being a well-characterized histologic phenotype, the molecular causes underlying such a distinctive cellular change are poorly understood. To identify potential genetic cause...
Chapter
Mitochondrial DNA encodes genes that are de facto metabolic enzymes and are currently emerging as pivotal players in the origin, progression, and outcome of human cancers. We here revise the multifaceted implications of mitochondrial mutations on the metabolic reprogramming cancer cells must undergo to adapt and proliferate. The sources of such mut...
Article
Full-text available
Leber's hereditary optic neuropathy (LHON) is associated with mitochondrial DNA (mtDNA) ND mutations that are mostly homoplasmic. However, these mutations are not sufficient to explain the peculiar features of penetrance and the tissue-specific expression of the disease and are believed to be causative in association with unknown environmental or o...
Article
Full-text available
HmtDB (http://www.hmtdb.uniba.it:8080/hmdb) is a open resource created to support population genetics and mitochondrial disease studies. The database hosts human mitochondrial genome sequences annotated with population and variability data, the latter being estimated through the application of the SiteVar software based on site-specific nucleotide...
Article
Mitochondrial DNA (mtDNA) mutations have been involved in disease, aging and cancer and furthermore exploited for evolutionary and forensic investigation. When investigating mtDNA mutations the peculiar aspects of mitochondrial genetics, such as heteroplasmy and threshold effect, require suitable approaches which must be sensitive enough to detect...

Projects

Projects (2)
Project
MToolBox is a highly automated bioinformatics pipeline to assemble and analyse human mitochondrial DNA from high throughput sequencing data. MToolBox includes an updated computational strategy to assemble mitochondrial genomes from Whole Exome and/or Genome Sequencing and an improved fragment-classify tool for haplogroup assignment, functional and prioritization analysis of mitochondrial variants. MToolBox provides pathogenicity scores, profiles of genome variability and disease-associations for mitochondrial variants. MToolBox provides also a Variant Call Format file (version 4.0) featuring, for the first time, allele-specific heteroplasmy.
Project
Mapping of expression Quantitative Traits Loci (eQTL) using RNA-seq and Whole Genome Sequencing data from more than 1000 cancer patients. Main aim of the project is to find the contribution of non-coding somatic and germline genomic variation to gene expression changes in cancer.