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Article ; Online: Genomic diversity of

Wilkinson, Daniel James / Dickins, Benjamin / Robinson, Karen / Winter, Jody Anne

2022 Volume 14, Issue 1, Page(s) 2152306

Abstract: Individuals infected ... ...

Abstract	Individuals infected with
MeSH term(s)	Humans ; Helicobacter pylori/genetics ; Helicobacter Infections/microbiology ; Gastrointestinal Microbiome ; Stomach/microbiology ; Genomics
Language	English
Publishing date	2022-12-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2575755-6
ISSN	1949-0984 ; 1949-0984
ISSN (online)	1949-0984
ISSN	1949-0984
DOI	10.1080/19490976.2022.2152306
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Article ; Online: Hyperactive neutrophil chemotaxis contributes to anti-tumor necrosis factor-α treatment resistance in inflammatory bowel disease.

Yau, Tung On / Vadakekolathu, Jayakumar / Foulds, Gemma Ann / Du, Guodong / Dickins, Benjamin / Polytarchou, Christos / Rutella, Sergio

Journal of gastroenterology and hepatology

2022 Volume 37, Issue 3, Page(s) 531–541

Abstract: Background and aim: Anti-tumor necrosis factor-α (anti-TNF-α) agents have been used for inflammatory bowel disease; however, it has up to 30% nonresponse rate. Identifying molecular pathways and finding reliable diagnostic biomarkers for patient ... ...

Abstract	Background and aim: Anti-tumor necrosis factor-α (anti-TNF-α) agents have been used for inflammatory bowel disease; however, it has up to 30% nonresponse rate. Identifying molecular pathways and finding reliable diagnostic biomarkers for patient response to anti-TNF-α treatment are needed. Methods: Publicly available transcriptomic data from inflammatory bowel disease patients receiving anti-TNF-α therapy were systemically collected and integrated. In silico flow cytometry approaches and Metascape were applied to evaluate immune cell populations and to perform gene enrichment analysis, respectively. Genes identified within enrichment pathways validated in neutrophils were tracked in an anti-TNF-α-treated animal model (with lipopolysaccharide-induced inflammation). The receiver operating characteristic curve was applied to all genes to identify the best prediction biomarkers. Results: A total of 449 samples were retrieved from control, baseline, and after primary anti-TNF-α therapy or placebo. No statistically significant differences were observed between anti-TNF-α treatment responders and nonresponders at baseline in immune microenvironment scores. Neutrophil, endothelial cell, and B-cell populations were higher in baseline nonresponders, and chemotaxis pathways may contribute to the treatment resistance. Genes related to chemotaxis pathways were significantly upregulated in lipopolysaccharide-induced neutrophils, but no statistically significant changes were observed in neutrophils treated with anti-TNF-α. Interleukin 13 receptor subunit alpha 2 (IL13RA2) is the best predictor (receiver operating characteristic curve: 80.7%, 95% confidence interval: 73.8-87.5%), with a sensitivity of 68.13% and specificity of 84.93%, and significantly higher in nonresponders compared with responders (P < 0.0001). Conclusions: Hyperactive neutrophil chemotaxis influences responses to anti-TNF-α treatment, and IL13RA2 is a potential biomarker to predict anti-TNF-α treatment response.
MeSH term(s)	Animals ; Chemotaxis/physiology ; Drug Resistance ; Humans ; Inflammatory Bowel Diseases/drug therapy ; Neutrophils/physiology ; Tumor Necrosis Factor Inhibitors/pharmacology ; Tumor Necrosis Factor-alpha/antagonists & inhibitors ; Tumor Necrosis Factor-alpha/drug effects
Chemical Substances	Tumor Necrosis Factor Inhibitors ; Tumor Necrosis Factor-alpha
Language	English
Publishing date	2022-02-02
Publishing country	Australia
Document type	Journal Article
ZDB-ID	632882-9
ISSN	1440-1746 ; 0815-9319
ISSN (online)	1440-1746
ISSN	0815-9319
DOI	10.1111/jgh.15764
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Article ; Online: Is genomics bad for you?

Dickins, Benjamin J A

The Behavioral and brain sciences

2012 Volume 35, Issue 5, Page(s) 364–365

Abstract: The plasticity of the genome complicates genetic causation but should be investigated from a functional perspective. Specific adaptive hypotheses are referenced in the target article, but it is also necessary to explain how the integrity of the genome is ...

Abstract	The plasticity of the genome complicates genetic causation but should be investigated from a functional perspective. Specific adaptive hypotheses are referenced in the target article, but it is also necessary to explain how the integrity of the genome is maintained despite processes that tend towards its diversification and degradation. These include the accumulation of deleterious changes and intragenomic conflict.
MeSH term(s)	Female ; Genetics, Behavioral ; Genomics ; Humans ; Pregnancy
Language	English
Publishing date	2012-10
Publishing country	England
Document type	Comment ; Journal Article
ZDB-ID	423721-3
ISSN	1469-1825 ; 0140-525X
ISSN (online)	1469-1825
ISSN	0140-525X
DOI	10.1017/S0140525X12000994
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Article ; Online: Faecal microRNAs as a non-invasive tool in the diagnosis of colonic adenomas and colorectal cancer: A meta-analysis.

Yau, Tung On / Tang, Ceen-Ming / Harriss, Elinor K / Dickins, Benjamin / Polytarchou, Christos

Scientific reports

2019 Volume 9, Issue 1, Page(s) 9491

Abstract: MicroRNAs (miRNAs) are proposed as potential biomarkers for the diagnosis of numerous diseases. Here, we performed a meta-analysis to evaluate the utility of faecal miRNAs as a non-invasive tool in colorectal cancer (CRC) screening. A systematic ... ...

Abstract	MicroRNAs (miRNAs) are proposed as potential biomarkers for the diagnosis of numerous diseases. Here, we performed a meta-analysis to evaluate the utility of faecal miRNAs as a non-invasive tool in colorectal cancer (CRC) screening. A systematic literature search, according to predetermined criteria, in five databases identified 17 research articles including 6475, 783 and 5569 faecal-based miRNA tests in CRC, adenoma patients and healthy individuals, respectively. Sensitivity, specificity, positive/negative likelihood and diagnostic odds ratios, area under curve (AUC), summary receiver operator characteristic (sROC) curves, association of individual or combinations of miRNAs to cancer stage and location, subgroup, meta-regression and Deeks' funnel plot asymmetry analyses were employed. Pooled miRNAs for CRC had an AUC of 0.811, with a sensitivity of 58.8% (95% confidence interval [CI]: 51.7-65.5%) and specificity of 84.8% (95% CI: 81.1-87.8%), whilst for colonic adenoma, it was 0.747, 57.3% (95% CI: 40.8-72.3%) and 76.1% (95% CI: 66.1-89.4%), respectively. The most reliable individual miRNA was miR-21, with an AUC of 0.843, sensitivity of 59.3% (95% CI: 26.3-85.6%) and specificity of 85.6% (95% CI: 72.2-93.2%). Paired stage analysis showed a better diagnostic accuracy in late stage CRC and sensitivity higher in distal than proximal CRC. In conclusion, faecal miR-21, miR-92a and their combination are promising non-invasive biomarkers for faecal-based CRC screening.
MeSH term(s)	Adenoma/diagnosis ; Adenoma/metabolism ; Colonic Neoplasms/diagnosis ; Colonic Neoplasms/metabolism ; Feces ; Female ; Humans ; Male ; MicroRNAs/metabolism ; RNA, Neoplasm/metabolism
Chemical Substances	MIRN21 microRNA, human ; MIRN92 microRNA, human ; MicroRNAs ; RNA, Neoplasm
Language	English
Publishing date	2019-07-01
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-45570-9
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Article ; Online: Cronobacter, the emergent bacterial pathogen Enterobacter sakazakii comes of age; MLST and whole genome sequence analysis.

Forsythe, Stephen J / Dickins, Benjamin / Jolley, Keith A

BMC genomics

2014 Volume 15, Page(s) 1121

Abstract: Background: Following the association of Cronobacter spp. to several publicized fatal outbreaks in neonatal intensive care units of meningitis and necrotising enterocolitis, the World Health Organization (WHO) in 2004 requested the establishment of a ... ...

Abstract	Background: Following the association of Cronobacter spp. to several publicized fatal outbreaks in neonatal intensive care units of meningitis and necrotising enterocolitis, the World Health Organization (WHO) in 2004 requested the establishment of a molecular typing scheme to enable the international control of the organism. This paper presents the application of Next Generation Sequencing (NGS) to Cronobacter which has led to the establishment of the Cronobacter PubMLST genome and sequence definition database (http://pubmlst.org/cronobacter/) containing over 1000 isolates with metadata along with the recognition of specific clonal lineages linked to neonatal meningitis and adult infections Results: Whole genome sequencing and multilocus sequence typing (MLST) has supports the formal recognition of the genus Cronobacter composed of seven species to replace the former single species Enterobacter sakazakii. Applying the 7-loci MLST scheme to 1007 strains revealed 298 definable sequence types, yet only C. sakazakii clonal complex 4 (CC4) was principally associated with neonatal meningitis. This clonal lineage has been confirmed using ribosomal-MLST (51-loci) and whole genome-MLST (1865 loci) to analyse 107 whole genomes via the Cronobacter PubMLST database. This database has enabled the retrospective analysis of historic cases and outbreaks following re-identification of those strains. Conclusions: The Cronobacter PubMLST database offers a central, open access, reliable sequence-based repository for researchers. It has the capacity to create new analysis schemes 'on the fly', and to integrate metadata (source, geographic distribution, clinical presentation). It is also expandable and adaptable to changes in taxonomy, and able to support the development of reliable detection methods of use to industry and regulatory authorities. Therefore it meets the WHO (2004) request for the establishment of a typing scheme for this emergent bacterial pathogen. Whole genome sequencing has additionally shown a range of potential virulence and environmental fitness traits which may account for the association of C. sakazakii CC4 pathogenicity, and propensity for neonatal CNS.
MeSH term(s)	Algorithms ; Cronobacter/classification ; Cronobacter/genetics ; Cronobacter sakazakii/classification ; Cronobacter sakazakii/genetics ; Databases, Genetic ; Genetic Linkage ; Genetic Loci ; Genome, Bacterial ; Genotype ; High-Throughput Nucleotide Sequencing ; Multilocus Sequence Typing ; Phylogeny ; Sequence Analysis, DNA
Language	English
Publishing date	2014-12-16
Publishing country	England
Document type	Journal Article
ZDB-ID	2041499-7
ISSN	1471-2164 ; 1471-2164
ISSN (online)	1471-2164
ISSN	1471-2164
DOI	10.1186/1471-2164-15-1121
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Article ; Online: High-resolution mapping of evolutionary trajectories in a phage.

Dickins, Benjamin / Nekrutenko, Anton

Genome biology and evolution

2009 Volume 1, Page(s) 294–307

Abstract: Experimental evolution in rapidly reproducing viruses offers a robust means to infer substitution trajectories during evolution. But with conventional approaches, this inference is limited by how many individual genotypes can be sampled from the ... ...

Abstract	Experimental evolution in rapidly reproducing viruses offers a robust means to infer substitution trajectories during evolution. But with conventional approaches, this inference is limited by how many individual genotypes can be sampled from the population at a time. Low-frequency changes are difficult to detect, potentially rendering early stages of adaptation unobservable. Here we circumvent this using short-read sequencing technology in a fine-grained analysis of polymorphism dynamics in the sentinel organism: a single-stranded DNA phage PhiX174. Nucleotide differences were educed from noise with binomial filtering methods that harnessed quality scores and separate data from brief phage amplifications. Remarkably, a significant degree of variation was observed in all samples including those grown in brief 2-h cultures. Sites previously reported as subject to high-frequency polymorphisms over a course of weeks exhibited monotonic increases in polymorphism frequency within hours in this study. Additionally, even with limitations imposed by the short length of sequencing reads, we were able to observe statistically significant linkage among polymorphic sites in evolved lineages. Additional parallels between replicate lineages were apparent in the sharing of polymorphic sites and in correlated polymorphism frequencies. Missense mutations were more likely to occur than silent mutations. This study offers the first glimpse into "real-time" substitution dynamics and offers a robust conceptual framework for future viral resequencing studies.
Language	English
Publishing date	2009-08-11
Publishing country	England
Document type	Journal Article
ZDB-ID	2495328-3
ISSN	1759-6653 ; 1759-6653
ISSN (online)	1759-6653
ISSN	1759-6653
DOI	10.1093/gbe/evp029
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Article ; Online: Immune dysfunction signatures predict outcomes and define checkpoint blockade-unresponsive microenvironments in acute myeloid leukemia.

The Journal of clinical investigation

2022 Volume 132, Issue 21

Abstract: BackgroundImmune exhaustion and senescence are dominant dysfunctional states of effector T cells and major hurdles for the success of cancer immunotherapy. In the current study, we characterized how acute myeloid leukemia (AML) promotes the generation of ...

Abstract	BackgroundImmune exhaustion and senescence are dominant dysfunctional states of effector T cells and major hurdles for the success of cancer immunotherapy. In the current study, we characterized how acute myeloid leukemia (AML) promotes the generation of senescent-like CD8+ T cells and whether they have prognostic relevance.METHODSWe analyzed NanoString, bulk RNA-Seq and single-cell RNA-Seq data from independent clinical cohorts comprising 1,896 patients treated with chemotherapy and/or immune checkpoint blockade (ICB).ResultsWe show that senescent-like bone marrow CD8+ T cells were impaired in killing autologous AML blasts and that their proportion negatively correlated with overall survival (OS). We defined what we believe to be new immune effector dysfunction (IED) signatures using 2 gene expression profiling platforms and reported that IED scores correlated with adverse-risk molecular lesions, stemness, and poor outcomes; these scores were a more powerful predictor of OS than 2017-ELN risk or leukemia stem cell (LSC17) scores. IED expression signatures also identified an ICB-unresponsive tumor microenvironment and predicted significantly shorter OS.ConclusionThe IED scores provided improved AML-risk stratification and could facilitate the delivery of personalized immunotherapies to patients who are most likely to benefit.TRIAL REGISTRATIONClinicalTrials.gov; NCT02845297.FUNDINGJohn and Lucille van Geest Foundation, Nottingham Trent University's Health & Wellbeing Strategic Research Theme, NIH/NCI P01CA225618, Genentech-imCORE ML40354, Qatar National Research Fund (NPRP8-2297-3-494).
MeSH term(s)	Humans ; Leukemia, Myeloid, Acute/therapy ; Leukemia, Myeloid, Acute/drug therapy ; Prognosis ; Immunotherapy ; Tumor Microenvironment ; CD8-Positive T-Lymphocytes ; Immune System Diseases
Language	English
Publishing date	2022-11-01
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI159579
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Article ; Online: Phylogeographic separation and formation of sexually discrete lineages in a global population of

Seecharran, Tristan / Kalin-Manttari, Laura / Koskela, Katja / Nikkari, Simo / Dickins, Benjamin / Corander, Jukka / Skurnik, Mikael / McNally, Alan

Microbial genomics

2017 Volume 3, Issue 10, Page(s) e000133

Abstract: ... Yersinia ... ...

Abstract	Yersinia pseudotuberculosis
MeSH term(s)	Animals ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; Gene Library ; Humans ; Phylogeny ; Whole Genome Sequencing ; Yersinia pseudotuberculosis/classification ; Yersinia pseudotuberculosis/genetics ; Yersinia pseudotuberculosis Infections/microbiology
Language	English
Publishing date	2017-09-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2835258-0
ISSN	2057-5858 ; 2057-5858
ISSN (online)	2057-5858
ISSN	2057-5858
DOI	10.1099/mgen.0.000133
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Article: (with research data) Elevated mitochondrial genome variation after 50 generations of radiation exposure in a wild rodent.

Baker, Robert J / Dickins, Benjamin / Wickliffe, Jeffrey K / Khan, Faisal A A / Gaschak, Sergey / Makova, Kateryna D / Phillips, Caleb D

Evolutionary applications

2017 Volume 10, Issue 8, Page(s) 784–791

Abstract: Currently, the effects of chronic, continuous low dose environmental irradiation on the mitochondrial genome of resident small mammals are unknown. Using the bank vole ( ...

Abstract	Currently, the effects of chronic, continuous low dose environmental irradiation on the mitochondrial genome of resident small mammals are unknown. Using the bank vole (
Language	English
Publishing date	2017-06-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2405496-3
ISSN	1752-4563 ; 1752-4571
ISSN (online)	1752-4563
ISSN	1752-4571
DOI	10.1111/eva.12475
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Article: Imprinted genes, postnatal adaptations and enduring effects on energy homeostasis.

Frontera, Margalida / Dickins, Benjamin / Plagge, Antonius / Kelsey, Gavin

Advances in experimental medicine and biology

2008 Volume 626, Page(s) 41–61

Abstract: The effects of imprinted genes on fetal growth and development have been firmly established. By and large, their roles conform to a conflict over provision of limited maternal resources to offspring, such that paternally expressed imprinted genes in ... ...

Abstract	The effects of imprinted genes on fetal growth and development have been firmly established. By and large, their roles conform to a conflict over provision of limited maternal resources to offspring, such that paternally expressed imprinted genes in offspring generally promote growth of the fetus, while maternally expressed imprinted genes tend to restrict it. It is comparatively recently that the important effects of imprinted genes in postnatal physiology have begun to be demonstrated, although a similar conflict may apply. In this chapter, we shall review some of the genetic evidence for imprinted effects on obesity, consider the action of selected imprinted genes in the central and peripheral control of energy homeostasis and look in detail at the intriguing effects of imprinting at the Gnas locus. Finally, we shall discuss whether these observations fit expectations of the prevailing theory for the existence of imprinting in mammals and go on to consider imprinted genes as targets for developmental programming.
MeSH term(s)	Adaptation, Physiological ; Animals ; Energy Metabolism ; Genomic Imprinting/genetics ; Homeostasis ; Postnatal Care
Language	English
Publishing date	2008-03-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-0-387-77576-0_4
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