ORCID Profile
0000-0003-0757-0711
Current Organisation
University of Aberdeen
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Publisher: Cold Spring Harbor Laboratory
Date: 18-07-2017
DOI: 10.1101/165118
Abstract: The presence of batch effects is a well-known problem in experimental data analysis, and single- cell RNA sequencing (scRNA-seq) is no exception. Large-scale scRNA-seq projects that generate data from different laboratories and at different times are rife with batch effects that can fatally compromise integration and interpretation of the data. In such cases, computational batch correction is critical for eliminating uninteresting technical factors and obtaining valid biological conclusions. However, existing methods assume that the composition of cell populations are either known or the same across batches. Here, we present a new strategy for batch correction based on the detection of mutual nearest neighbours in the high-dimensional expression space. Our approach does not rely on pre-defined or equal population compositions across batches, only requiring that a subset of the population be shared between batches. We demonstrate the superiority of our approach over existing methods on a range of simulated and real scRNA-seq data sets. We also show how our method can be applied to integrate scRNA-seq data from two separate studies of early embryonic development.
Publisher: Elsevier BV
Date: 06-2021
Publisher: Elsevier BV
Date: 03-2022
Publisher: Springer Science and Business Media LLC
Date: 02-04-2018
DOI: 10.1038/NBT.4091
Publisher: Springer Science and Business Media LLC
Date: 2010
DOI: 10.1186/AR2969
Publisher: Elsevier BV
Date: 03-2022
Publisher: Wiley
Date: 24-09-2013
DOI: 10.1002/ART.38064
Abstract: There is increasing evidence to indicate that genetic factors contribute significantly to radiologic joint damage in rheumatoid arthritis (RA). The aim of the present study was to determine whether genotypes of 10 recently identified RA susceptibility loci are associated with radiologic severity. A 2-stage study was performed using 3 Northern European RA populations: a British cross-sectional population (discovery cohort n=885) and the Leiden Early Arthritis Clinic (EAC) cohort (n=581) and Yorkshire Early Arthritis Register (YEAR) cohort (n=418) (validation cohorts). Radiologic damage was assessed using a modified Larsen method for scoring radiographs (in the discovery cohort) or modified Sharp/van der Heijde score (in the 2 validation cohorts). A meta-analysis was performed to bring together the evidence from the 3 studies, using data on radiologic severity of joint damage from a single time point. An allele-dose association of rs26232 was present in the discovery population (P=4×10(-4)) the median modified Larsen scores of radiologic joint damage per genotype were 31 (for those with CC), 27 (for those with CT), and 16 (for those with TT). The allele-dose association of rs26232 was replicated in both the Leiden EAC cohort during the initial 7 years of RA (P=0.04) and the YEAR cohort (P=0.039). In a fixed-effects meta-analysis of all 3 studies, the per T allele effect on the ratio of radiologic severity scores was 0.90 (95% confidence interval 0.84, 0.96 P=0.004). The variant rs26232, in the first intron of the C5orf30 locus, is associated with the severity of radiologic damage in RA and is independent of established prognostic biomarkers. The biologic activities of C5orf30 are unknown, but our genetic data suggest that it is involved in mediating joint damage in RA.
Publisher: Springer Science and Business Media LLC
Date: 20-04-2021
DOI: 10.1038/S41591-021-01329-2
Abstract: Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts ( CD16 + C1QA/B/C + ) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34 + hematopoietic stem rogenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8 + T cells and an increased ratio of CD8 + effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy.
Publisher: Springer Science and Business Media LLC
Date: 08-09-2021
DOI: 10.1038/S41586-021-03852-1
Abstract: The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung’s disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Michael Morgan.