Andrew Farrell
A5017789917- Cancer Cells and Metastasis
- Cancer Genomics and Diagnostics
- Proteoglycans and glycosaminoglycans research
- Toxoplasma gondii Research Studies
- Genomic variations and chromosomal abnormalities
- Genomics and Rare Diseases
- Fibroblast Growth Factor Research
- Cytomegalovirus and herpesvirus research
- Congenital heart defects research
- Breast Cancer Treatment Studies
- Herpesvirus Infections and Treatments
- Global Cancer Incidence and Screening
- Genomics and Phylogenetic Studies
- Acute Ischemic Stroke Management
- Congenital Diaphragmatic Hernia Studies
- Chromosomal and Genetic Variations
- CRISPR and Genetic Engineering
- Sarcoma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Metastasis and carcinoma case studies
- Tracheal and airway disorders
- Autism Spectrum Disorder Research
- Parasitic Infections and Diagnostics
- PARP inhibition in cancer therapy
- DNA Repair Mechanisms
National Health Service
2024
Walter and Eliza Hall Institute of Medical Research
2022-2024
University of Utah
2017-2023
The University of Melbourne
2023
Star Center
2017-2022
Huntsman Cancer Institute
2021
University of Glasgow
2020
Boston College
2012-2015
Wirral University Teaching Hospital NHS Foundation Trust
2014
Bristol Royal Infirmary
1979
The incomplete identification of structural variants (SVs) from whole-genome sequencing data limits studies human genetic diversity and disease association. Here, we apply a suite long-read, short-read, strand-specific technologies, optical mapping, variant discovery algorithms to comprehensively analyze three trios define the full spectrum variation in haplotype-resolved manner. We identify 818,054 indel (<50 bp) 27,622 SVs (≥50 per genome. also discover 156 inversions genome 58 intersect...
Parasite Invasion Strategy Exocytosis is essential to the lytic cycle of apicomplexan parasites and required for pathogenesis toxoplasmosis malaria. DOC2 proteins recruit membrane fusion machinery exocytosis in a Ca 2+ -dependent fashion. Farrell et al. (p. 218 ) describe phenotype Toxoplasma gondii conditional mutant impaired host cell invasion egress. The was explained by defect secretion micronemes, an apicomplexan-specific organelle that contains adhesion proteins. A T. Doc2 gene...
Short tandem repeats (STRs) and variable number (VNTRs) are important sources of natural disease-causing variation, yet they have been problematic to resolve in reference genomes genotype with short-read technology. We created a framework model the evolution instability STRs VNTRs apes. phased assembled 3 ape (chimpanzee, gorilla, orangutan) using long-read 10x Genomics linked-read sequence data for 21,442 human discovered 6 haplotype-resolved assemblies Yoruban, Chinese, Puerto Rican...
Germline mutation rates in humans have been estimated for a variety of types, including single-nucleotide and large structural variants. Here, we directly measure the germline retrotransposition rate three active retrotransposon elements: L1, Alu , SVA. We used tools calling mobile element insertions (MEIs) (MELT, RUFUS, TranSurVeyor) on blood-derived whole-genome sequence (WGS) data from 599 CEPH individuals, comprising 33 three-generation pedigrees. identified 26 de novo MEIs 437 births....
Our aim was to identify whether particular subgroups of patients had an unacceptably high risk symptomatic intracranial hemorrhage or low chance benefit when treated with alteplase (recombinant tissue-type plasminogen activator).Third International Stroke Trial international randomized trial the intravenous (IV) recombinant activator (0.9 mg/kg) versus control in 3035 (1515 1520) patients. We analyzed effect on 6-month functional outcome, early death, and (both ≤7 days). tested for any...
Abstract Early infantile epileptic encephalopathy (EIEE) is a devastating epilepsy syndrome with onset in the first months of life. Although mutations more than 50 different genes are known to cause EIEE, current diagnostic yields gene panel tests or whole-exome sequencing below 60%. We applied whole-genome analysis (WGA) consisting and comprehensive variant discovery approaches cohort 14 EIEE subjects for whom prior genetic had not yielded diagnosis. identified both de novo point INDEL...
This method is based on differences in the resistance of strains Candida albicans to a number selected chemicals used at critical concentrations. The was applied isolates from patients undergoing treatment for vaginal infection and it found that particular were consistently present individual patients, both different specimens occasions. It also some harboured more than one strain C. . Inconsistencies resistograms certain tested occasions resolved when amount inoculum test further standardized.
ABSTRACT The incomplete identification of structural variants (SVs) from whole-genome sequencing data limits studies human genetic diversity and disease association. Here, we apply a suite long-read, short-read, strand-specific technologies, optical mapping, variant discovery algorithms to comprehensively analyze three parent–child trios define the full spectrum variation in haplotype-resolved manner. We identify 818,054 indel (<50 bp) 27,622 SVs (≥50 per genome. also discover 156...
Abstract Background Toxoplasma gondii has a largely clonal population in North America and Europe, with types I, II III lineages accounting for the majority of strains isolated from patients. RH, particular type I strain, is most frequently used to characterize biology. However, compared other strains, RH unique characteristics such as faster growth, increased extracellular survival rate inability form orally infectious cysts. Thus, identify candidate genes that could account these parasite...
The simultaneous targeting of host and pathogen processes represents an untapped approach for the treatment intracellular infections. Hypoxia-inducible factor-1 (HIF-1) is a cell transcription factor that activated by required growth protozoan parasite Toxoplasma gondii at physiological oxygen levels. Parasite activation HIF-1 blocked inhibiting family closely related Activin-Like Kinase (ALK) receptors ALK4, ALK5, ALK7, which was determined in part use ALK4,5,7 inhibitor named SB505124....
Next generation sequencing is helping to overcome limitations in organisms less accessible classical or reverse genetic methods by facilitating whole genome mutational analysis studies. One traditionally intractable group, the Apicomplexa, contains several important pathogenic protozoan parasites, including Plasmodium species that cause malaria.Here we apply relatively model apicomplexan, Toxoplasma gondii, optimize forward for chemical mutagenesis using N-ethyl-N-nitrosourea (ENU) and...
Evolve and resequencing (E&R) was applied to lab adaptation of Toxoplasma gondii for over 1,500 generations with the goal mapping host-independent in vitro virulence traits. Phenotypic assessments steps across lytic cycle revealed that only traits needed extracellular milieu evolved. Nonsynonymous single-nucleotide polymorphisms (SNPs) one gene, a P4 flippase, fixated two different evolving populations, whereas dramatic changes transcriptional signature parasites were identified. Newly...
Ovarian carcinosarcoma (OCS) is an aggressive and rare tumor type with limited treatment options. OCS hypothesized to develop via the combination theory, a single progenitor resulting in carcinomatous sarcomatous components, or alternatively conversion component developing from through epithelial-to-mesenchymal transition (EMT). In this study, we analyzed DNA variants isolated carcinoma sarcoma components show that 18 women monoclonal. RNA sequencing indicated were more mesenchymal when...
splice isoforms Δ11 and Δ11q can contribute to PARP inhibitor (PARPi) resistance by splicing-out the mutation-containing exon, producing truncated, partially-functional proteins. However, clinical impact underlying drivers of
Summary Genomic studies to date in autism spectrum disorder (ASD) have largely focused on newly arising mutations that disrupt protein coding sequence and strongly influence risk. We evaluate the contribution of noncoding regulatory variation across size frequency through whole genome sequencing 519 ASD cases, their unaffected sibling controls, parents. Cases carry a small excess de novo (1.02-fold) variants, which is not significant after correcting for paternal age. Assessing 51,801...
Introduction Hereditary haemorrhagic telangiectasia (HHT) is a genetically heterogeneous disorder caused by mutations in the genes ENG , ACVRL1 and SMAD4. Yet genetic cause remains unknown for some families even after exhaustive exome analysis. We hypothesised that non-coding regions of known HHT may harbour variants disrupt splicing these cases. Methods DNA from 35 individuals with clinical findings 2 healthy controls 13 underwent whole genome sequencing. Additionally, 87 unrelated cases...
Genetic disorders contribute to significant morbidity and mortality in critically ill newborns. Despite advances genome sequencing technologies, a majority of neonatal cases remain unsolved. Complex structural variants (SVs) often elude conventional variant calling pipelines will explain portion these unsolved cases.As part the Utah NeoSeq project, we used research-based, rapid whole-genome (WGS) protocol investigate genomic etiology for newborn with left-sided congenital diaphragmatic...
Congenital myasthenic syndrome (CMS) is a group of 32 disorders involving genetic dysfunction at the neuromuscular junction resulting in skeletal muscle weakness that worsens with physical activity. Precise diagnosis and molecular subtype identification are critical for treatment as medication one may exacerbate disease another (Engel et al., Lancet Neurol 14: 420 [2015]; Finsterer, Orphanet J Rare Dis 57 [2019]; Prior Ghosh, Child 36: 610 [2021]). The SNAP25- related CMS (congenital 18,...
Metastatic breast cancer is a deadly disease with low 5-year survival rate. Tracking metastatic spread in living patients difficult and thus poorly understood. Via rapid autopsy, we have collected 30 tumor samples over 3 timepoints across 8 organs from triple-negative patient. The large number of sites sampled, together deep whole-genome sequencing advanced computational analysis, allowed us to comprehensively reconstruct the tumor's evolution at subclonal resolution. most unique, previously...
The diaphragm is critical for respiration and separation of the thoracic abdominal cavities, defects in development are cause congenital diaphragmatic hernias (CDH), a common often lethal birth defect. genetic etiology CDH complex. Single-nucleotide variants (SNVs), insertions/deletions (indels), structural (SVs) more than 150 genes have been associated with CDH, although few recurrently mutated multiple individuals incompletely penetrant. This suggests that combination, other...